A natural product is a natural

compound Compound may refer to: Architecture and built environments * Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fence or wall ** Compound (fortification), a version of the above fortified with defensive struc ...

or substance produced by a living organism—that is, found in

nature Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...

. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by

chemical synthesis As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mod ...

(both

semisynthesis Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...

and

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

) and have played a central role in the development of the field of

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...

by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients. Within the field of

, the definition of natural products is usually restricted to

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...

s isolated from natural sources that are produced by the pathways of primary or

secondary metabolism Secondary metabolism (also called specialized metabolism) is a term for pathways and small molecule products of metabolism that are involved in ecological interactions, but are not absolutely required for the survival of the organism. These molecu ...

. Within the field of

medicinal chemistry Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developme ...

, the definition is often further restricted to secondary metabolites. Secondary metabolites (or specialized metabolites) are not essential for survival, but nevertheless provide organisms that produce them an evolutionary advantage. Many secondary metabolites are cytotoxic and have been selected and optimized through evolution for use as "chemical warfare" agents against prey, predators, and competing organisms. Secondary or specialized metabolites are often unique to species, which is contrasted to primary metabolites which have broad use across kingdoms. Secondary metabolites are marked by chemical complexity which is why they are of such interest to chemists. Natural sources may lead to

basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...

on potential bioactive components for commercial development as

lead compound A lead compound (, i.e. a "leading" compound, not to be confused with various compounds of the metallic element lead) in drug discovery is a chemical compound that has pharmacology, pharmacological or biological activity likely to be therapeutical ...

s in drug discovery. Although natural products have inspired numerous drugs,

drug development Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for re ...

from natural sources has received declining attention in the 21st century by pharmaceutical companies, partly due to unreliable access and supply, intellectual property, cost, and profit concerns, seasonal or environmental variability of composition, and loss of sources due to rising

extinction Extinction is the termination of a kind of organism or of a group of kinds (taxon), usually a species. The moment of extinction is generally considered to be the death of the last individual of the species, although the capacity to breed and ...

rates.

Classes

The broadest definition of natural product is anything that is produced by life, and includes the likes of

biotic material Biotic material or biological derived material is any material that originates from living organisms. Most such materials contain carbon and are capable of decay. The earliest life on Earth arose at least 3.5 billion years ago.Schopf, JW, Kudr ...

s (e.g. wood, silk),

bio-based material A bio-based material is a material intentionally made from substances derived from living (or once-living) organisms. These materials are sometimes referred to as biomaterials, but this word also has another meaning. Strictly the definition could ...

s (e.g.

bioplastic Bioplastics are plastic materials produced from renewable biomass sources, such as vegetable fats and oils, corn starch, straw, woodchips, sawdust, recycled food waste, etc. Some bioplastics are obtained by processing directly from natural bi ...

s, cornstarch), bodily fluids (e.g. milk, plant exudates), and other natural materials (e.g. soil, coal). Natural products may be classified according to their biological function, biosynthetic pathway, or source. Depending on the sources, the number of known natural product molecules ranges between 300,000 and 400,000.

Function

Following

Albrecht Kossel Ludwig Karl Martin Leonhard Albrecht Kossel (; 16 September 1853 – 5 July 1927) was a German biochemist and pioneer in the study of genetics. He was awarded the Nobel Prize for Physiology or Medicine in 1910 for his work in determining the ch ...

's original proposal in 1891, natural products are often divided into two major classes, the primary and secondary metabolites. Primary metabolites have an intrinsic function that is essential to the survival of the organism that produces them. Secondary metabolites in contrast have an extrinsic function that mainly affects other organisms. Secondary metabolites are not essential to survival but do increase the competitiveness of the organism within its environment. Because of their ability to modulate biochemical and signal transduction pathways, some secondary metabolites have useful medicinal properties. Natural products especially within the field of

are often defined as primary and secondary metabolites. A more restrictive definition limiting natural products to secondary metabolites is commonly used within the fields of

and pharmacognosy.

Primary metabolites

Primary metabolites as defined by Kossel are components of basic metabolic pathways that are required for life. They are associated with essential cellular functions such as nutrient assimilation, energy production, and growth/development. They have a wide species distribution that span many phyla and frequently more than one

kingdom Kingdom commonly refers to: * A monarchy ruled by a king or queen * Kingdom (biology), a category in biological taxonomy Kingdom may also refer to: Arts and media Television * ''Kingdom'' (British TV series), a 2007 British television drama s ...

. Primary metabolites include the basic building blocks of life:

carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

s, and nucleic acids. Primary metabolites that are involved with energy production include

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...

and photosynthetic

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s. Enzymes in turn are composed of

s and often non-peptidic cofactors that are essential for enzyme function. The basic structure of cells and of organisms are also composed of primary metabolites. These include cell membranes (e.g. phospholipids), cell walls (e.g.

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

, chitin), and

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...

s (proteins). Primary metabolite enzymatic cofactors include members of the

vitamin B B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coex ...

family.

Vitamin B1 Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thia ...

as thiamine diphosphate is a coenzyme for

pyruvate dehydrogenase Pyruvate dehydrogenase is an enzyme that catalyzes the reaction of pyruvate and a lipoamide to give the acetylated dihydrolipoamide and carbon dioxide. The conversion requires the coenzyme thiamine pyrophosphate. Pyruvate dehydrogenase is u ...

, 2-oxoglutarate dehydrogenase, and

transketolase Transketolase (abbreviated as TK) is an enzyme that is encoded by the TKT gene. It participates in both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis. Transketolase catalyzes two important reactions, whic ...

which are all involved in carbohydrate metabolism.

Vitamin B2 Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in e ...

(riboflavin) is a constituent of FMN and FAD which are necessary for many redox reactions.

Vitamin B3 Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms or vitamers: niacin (nicotinic acid), nicotinamide (niacinamide), and nicotinamide riboside. All three forms of vitamin B3 are converted within the bo ...

(nicotinic acid or niacin), synthesized from tryptophan is a component of the coenzymes NAD and

NADP Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require N ...

which in turn are required for electron transport in the

Krebs cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

, oxidative phosphorylation, as well as many other redox reactions.

Vitamin B5 Pantothenic acid, also called vitamin B5 is a water-soluble B vitamin and therefore an essential nutrient. All animals require pantothenic acid in order to synthesize coenzyme A (CoA) – essential for fatty acid metabolism – as well as to, ...

(pantothenic acid) is a constituent of coenzyme A, a basic component of carbohydrate and amino acid metabolism as well as the biosynthesis of fatty acids and polyketides.

Vitamin B6 Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., " vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosp ...

(pyridoxol, pyridoxal, and pyridoxamine) as pyridoxal 5′-phosphate is a cofactor for many enzymes especially transaminases involve in amino acid metabolism.

Vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...

(cobalamins) contain a

corrin Corrin is a heterocyclic compound. It is the parent macrocycle related to the substituted derivative that is found in vitamin B12. Its name reflects that it is the "core" of vitamin B12 (cobalamins).Nelson, D. L.; Cox, M. M. "Lehninger, Princi ...

ring similar in structure to

porphyrin Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical com ...

and is an essential coenzyme for the catabolism of fatty acids as well for the biosynthesis of methionine. DNA and RNA which store and transmit

genetic information A nucleic acid sequence is a succession of bases signified by a series of a set of five different letters that indicate the order of nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. By convention, sequences are usu ...

are composed of nucleic acid primary metabolites. First messengers are signaling molecules that control

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

or cellular differentiation. These signaling molecules include hormones and growth factors in turn are composed of peptides,

biogenic amine A biogenic amine is a biogenic substance with one or more amine groups. They are basic nitrogenous compounds formed mainly by decarboxylation of amino acids or by amination and transamination of aldehydes and ketones. Biogenic amines are organic ...

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...

s, auxins,

gibberellin Gibberellins (GAs) are plant hormones that regulate various developmental processes, including stem elongation, germination, dormancy, flowering, flower development, and leaf and fruit senescence. GAs are one of the longest-known classes of plan ...

s etc. These first messengers interact with cellular receptors which are composed of proteins. Cellular receptors in turn activate second messengers are used to relay the extracellular message to intracellular targets. These signaling molecules include the primary metabolites

cyclic nucleotide A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, a ...

diacyl glycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as su ...

etc.

Secondary metabolites

Secondary in contrast to primary metabolites are dispensable and not absolutely required for survival. Furthermore, secondary metabolites typically have a narrow species distribution. Secondary metabolites have a broad range of functions. These include

pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

s that act as social signaling molecules with other individuals of the same species, communication molecules that attract and activate symbiotic organisms, agents that solubilize and transport nutrients (

siderophores Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is no ...

etc.), and competitive weapons ( repellants,

venoms Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...

, toxins etc.) that are used against competitors, prey, and predators. For many other secondary metabolites, the function is unknown. One hypothesis is that they confer a competitive advantage to the organism that produces them. An alternative view is that, in analogy to the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...

, these secondary metabolites have no specific function, but having the machinery in place to produce these diverse chemical structures is important and a few secondary metabolites are therefore produced and selected for. General structural classes of secondary metabolites include

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

s, phenylpropanoids,

polyketide Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

s, and

terpenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes" ...

Biosynthesis

The biosynthetic pathways leading to the major classes of natural products are described below. *

Photosynthesis Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...

or gluconeogenesis → monosaccharides → polysaccharides (

cellulose Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell w ...

, chitin, glycogen etc.) * Acetate pathway →

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

s and

s *

Shikimate pathway The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...

→ aromatic amino acids and phenylpropanoids *

Mevalonate pathway The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl ...

and methyletrythritol phosphate pathway →

s and steroids * Amino acids →

Carbohydrates

Carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...

s are an essential energy source for most life forms. In addition, polysaccharides formed from simpler carbohydrates are important structural components of many organisms such the cell walls of bacteria and plants. Carbohydrate are the products of plant

photosynthesis Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...

and animal gluconeogenesis. Photosynthesis produces initially 3-phosphoglyceraldehyde, a three carbon atom containing sugar (a

triose A triose is a monosaccharide, or simple sugar, containing three carbon atoms. There are only three possible trioses (including dihydroxyacetone): L-glyceraldehyde and D-glyceraldehyde, the two enantiomers of glyceraldehyde, which are aldotrios ...

). This triose in turn may be converted into

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

(a six carbon atom containing sugar) or a variety of

pentose In chemistry, a pentose is a monosaccharide (simple sugar) with five carbon atoms. The chemical formula of many pentoses is , and their molecular weight is 150.13 g/mol.Calvin cycle. In animals, the three carbon precursors lactate or

glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...

can be converted into pyruvate which in turn can be converted into carbohydrates in the liver.

Fatty acids and polyketides

Through the process of glycolysis sugars are broken down into acetyl-CoA. In an ATP dependent enzymatically catalyzed reaction, acetyl-CoA is carboxylated to form malonyl-CoA. Acetyl-CoA and malonyl-CoA undergo a

Claisen condensation The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β-diketone. It is named after Ra ...

with lose of carbon dioxide to form

acetoacetyl-CoA Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis (ketogenesis) pathway of the liver. In the ketone bodies digestion ...

. Additional condensation reactions produce successively higher molecular weight poly-β-keto chains which are then converted into other

s. The polyketide class of natural products have diverse structures and functions and include prostaglandins and

macrolide antibiotic The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macr ...

s. One molecule of acetyl-CoA (the "starter unit") and several molecules malonyl-CoA (the "extender units") are condensed by

fatty acid synthase Fatty acid synthase (FAS) is an enzyme that in humans is encoded by the ''FASN'' gene. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis. It is not a single enzyme but a whole enzymatic system composed of two iden ...

to produce

s. Fatty acid are essential components of lipid bilayers that form cell membranes as well as fat energy stores in animals.

Sources

Natural products may be extracted from the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s, tissues, and secretions of

microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

s, plants and animals. A crude ( unfractionated) extract from any one of these sources will contain a range of structurally diverse and often novel chemical compounds. Chemical diversity in nature is based on biological diversity, so researchers collect samples from around the world to analyze and evaluate in drug discovery screens or

bioassays An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...

. This effort to search for biologically active natural products is known as

bioprospecting Bioprospecting (also known as biodiversity prospecting) is the exploration of natural sources for small molecules, macromolecules and biochemical and genetic information that could be developed into commercially valuable products for the agric ...

. Pharmacognosy provides the tools to detect, isolate and identify bioactive natural products that could be developed for medicinal use. When an "active principle" is isolated from a traditional medicine or other biological material, this is known as a "hit". Subsequent scientific and legal work is then performed to validate the hit (eg. elucidation of

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

, confirmation that there is no intellectual property conflict). This is followed by the hit to lead stage of drug discovery, where derivatives of the active compound are produced in an attempt to improve its

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

and

safety Safety is the state of being "safe", the condition of being protected from harm or other danger. Safety can also refer to the control of recognized hazards in order to achieve an acceptable level of risk. Meanings There are two slightly dif ...

. In this and related ways, modern medicines can be developed directly from natural sources. Although traditional medicines and other biological material are considered an excellent source of novel compounds, the extraction and isolation of these compounds can be a slow, expensive and inefficient process. For large scale manufacture therefore, attempts may be made to produce the new compound by total synthesis or semisynthesis. Because natural products are generally

secondary metabolite Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norma ...

s with complex

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...

s, their total/semisynthesis is not always commercially viable. In these cases, efforts can be made to design simpler analogues with comparable potency and safety that are amenable to total/semisynthesis.

Prokaryotic

Bacteria

The serendipitous discovery and subsequent clinical success of penicillin prompted a large-scale search for other environmental microorganisms that might produce anti-infective natural products. Soil and water samples were collected from all over the world, leading to the discovery of

streptomycin Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, ''Mycobacterium avium'' complex, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever. F ...

(derived from ''

Streptomyces griseus ''Streptomyces griseus'' is a species of bacteria in the genus ''Streptomyces'' commonly found in soil. A few strains have been also reported from deep-sea sediments. It is a Gram-positive bacterium with high GC content. Along with most other ...

''), and the realization that bacteria, not just fungi, represent an important source of pharmacologically active natural products. This, in turn, led to the development of an impressive arsenal of antibacterial and antifungal agents including

amphotericin B Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...

, chloramphenicol,

daptomycin Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms. Daptomycin was removed from the World Health Organiza ...

and

tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...

(from '' Streptomyces''

spp. In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate se ...

), the

polymyxin Polymyxins are antibiotics. Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules ...

s (from ''

Paenibacillus polymyxa ''Paenibacillus polymyxa'', also known as ''Bacillus polymyxa'', is a Gram-positive bacterium capable of fixing nitrogen. It is found in soil, plant tissues, marine sediments and hot springs. It may have a role in forest ecosystems and potentia ...

''), and the rifamycins (from ''

Amycolatopsis rifamycinica ''Amycolatopsis rifamycinica'' is a species of Gram-positive bacteria in the genus '' Amycolatopsis''. It produces the rifamycin antibiotics (''e.g.'', rifamycin SV), which are used to treat mycobacterial diseases such as tuberculosis and lep ...

''). Antiparasitic and antiviral drugs have similarly been derived from bacterial metabolites. Although most of the drugs derived from bacteria are employed as anti-infectives, some have found use in other fields of medicine. Botulinum toxin (from ''

Clostridium botulinum ''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum. The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans ...

'') and

bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...

(from ''

Streptomyces verticillus ''Streptomyces verticillus'' is a species of Gram-positive bacteria in the genus ''Streptomyces''. Whilst screening fermentation broths of this species for bioactivity in the early 1960s, Hamao Umezawa and colleagues at the Institute of Microbi ...

'') are two examples. Botulinum, the neurotoxin responsible for

botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...

, can be injected into specific muscles (such as those controlling the eyelid) to prevent

muscle spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscl ...

. Also, the

glycopeptide Glycopeptides are peptides that contain carbohydrate moieties ( glycans) covalently attached to the side chains of the amino acid residues that constitute the peptide. Over the past few decades it has been recognised that glycans on cell surfa ...

bleomycin is used for the treatment of several cancers including

Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...

head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

, and

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an ...

. Newer trends in the field include the metabolic profiling and isolation of natural products from novel bacterial species present in underexplored environments. Examples include symbionts or

endophytes An endophyte is an endosymbiont, often a bacterium or fungus, that lives within a plant for at least part of its life cycle without causing apparent disease. Endophytes are ubiquitous and have been found in all species of plants studied to date; h ...

from tropical environments, subterranean bacteria found deep underground via mining/drilling, and marine bacteria.

Archaea

Because many Archaea have adapted to life in extreme environments such as polar regions, hot springs, acidic springs, alkaline springs, salt lakes, and the

high pressure In science and engineering the study of high pressure examines its effects on materials and the design and construction of devices, such as a diamond anvil cell, which can create high pressure. By ''high pressure'' is usually meant pressures of th ...

deep ocean water Deep ocean water (DOW) is the name for cold, salty water found deep below the surface of Earth's oceans. Ocean water differs in temperature and salinity. Warm surface water is generally saltier than the cooler deep or polar waters; in polar regio ...

, they possess enzymes that are functional under quite unusual conditions. These enzymes are of potential use in the food,

chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., w ...

, and

pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field an ...

industries, where biotechnological processes frequently involve high temperatures, extremes of pH, high salt concentrations, and / or high pressure. Examples of enzymes identified to date include

amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...

pullulanase Pullulanase (, ''limit dextrinase'', ''amylopectin 6-glucanohydrolase'', ''bacterial debranching enzyme'', ''debranching enzyme'', ''alpha-dextrin endo-1,6-alpha-glucosidase'', ''R-enzyme'', ''pullulan alpha-1,6-glucanohydrolase'') is a specific ki ...

cyclodextrin glycosyltransferase In enzymology, a cyclomaltodextrin glucanotransferase (also cyclodextrin glycosyl transferase or CGTase for short) () is an enzyme that catalyzes the chemical reaction of cyclizing part of a 1,4-alpha-D-glucan molecule through the formation of a ...

cellulase Cellulase (EC 3.2.1.4; systematic name 4-β-D-glucan 4-glucanohydrolase) is any of several enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze cellulolysis, the decomposition of cellulose and of some related polysacchar ...

xylanase Endo-1,4-β-xylanase (EC 3.2.1.8, systematic name 4-β-D-xylan xylanohydrolase) is any of a class of enzymes that degrade the linear polysaccharide xylan into xylose, thus breaking down hemicellulose, one of the major components of plant cell ...

chitinase Chitinases (EC 3.2.1.14, chitodextrinase, 1,4-β-poly-N-acetylglucosaminidase, poly-β-glucosaminidase, β-1,4-poly-N-acetyl glucosamidinase, poly ,4-(N-acetyl-β-D-glucosaminide)glycanohydrolase, (1→4)-2-acetamido-2-deoxy-β-D-glucan glycano ...

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NA ...

, and

esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...

s. Archaea represent a source of novel

chemical compounds A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

also, for example isoprenyl glycerol ethers 1 and 2 from '' Thermococcus'' S557 and '' Methanocaldococcus jannaschii'', respectively.

Eukaryotic

Fungi

Several anti-infective medications have been derived from fungi including penicillin and the

cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...

(antibacterial drugs from ''

Penicillium rubens ''Penicillium rubens'' is a species of fungus in the genus ''Penicillium'' and was the first species known to produce the antibiotic penicillin. It was first described by Philibert Melchior Joseph Ehi Biourge in 1923. For the discovery of penici ...

'' and '' Cephalosporium acremonium'', respectively) and

griseofulvin Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth. C ...

(an antifungal drug from ''

Penicillium griseofulvum ''Penicillium griseofulvum'' is a species of the genus of ''Penicillium'' which produces patulin, penifulvin A, cyclopiazonic acid, roquefortine C, shikimic acid, griseofulvin, and 6-Methylsalicylic acid (via a polyketide synthase Polyketides ...

''). Other medicinally useful fungal metabolites include

lovastatin Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth. ...

(from ''

Pleurotus ostreatus ''Pleurotus ostreatus'', the oyster mushroom, oyster fungus, or hiratake, is a common edible mushroom. It was first cultivated in Germany as a subsistence measure during World War I and is now grown commercially around the world for food. It is ...

''), which became a lead for a series of drugs that lower

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

levels,

cyclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disea ...

(from ''

Tolypocladium inflatum ''Tolypocladium inflatum'' is an ascomycete fungus originally isolated from a Norwegian soil sample that, under certain conditions, produces the immunosuppressant drug ciclosporin. In its sexual stage ( teleomorph) it is a parasite on scarab b ...

''), which is used to suppress the

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

after

organ transplant Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...

operations, and

ergometrine Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used ei ...

(from '' Claviceps'' spp.), which acts as a

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...

, and is used to prevent bleeding after childbirth.

Asperlicin Asperlicin is a mycotoxin, derived from the fungus '' Aspergillus alliaceus''. It acts as a selective antagonist for the cholecystokinin receptor CCKA, and has been used as a lead compound A lead compound (, i.e. a "leading" compound, not to be ...

(from '' Aspergillus alliaceus'') is another example. Asperlicin is a novel antagonist of

cholecystokinin Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat an ...

, a neurotransmitter thought to be involved in

panic attacks Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...

, and could potentially be used to treat

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

Plants

Plants are a major source of complex and highly structurally diverse chemical compounds (

phytochemicals Phytochemicals are chemical compounds produced by plants, generally to help them resist fungi, bacteria and plant virus infections, and also consumption by insects and other animals. The name comes . Some phytochemicals have been used as poison ...

), this structural diversity attributed in part to the

natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...

of organisms producing potent compounds to deter

herbivory A herbivore is an animal anatomically and physiologically adapted to eating plant material, for example foliage or marine algae, for the main component of its diet. As a result of their plant diet, herbivorous animals typically have mouthpart ...

( feeding deterrents). Major classes of phytochemical include

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...

polyphenol Polyphenols () are a large family of naturally occurring organic compounds characterized by multiples of phenol units. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some o ...

tannin Tannins (or tannoids) are a class of astringent, polyphenolic biomolecules that bind to and precipitate proteins and various other organic compounds including amino acids and alkaloids. The term ''tannin'' (from Anglo-Norman ''tanner'' ...

terpene Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ...

s, and

s. Though the number of plants that have been extensively studied is relatively small, many pharmacologically active natural products have already been identified. Clinically useful examples include the

anticancer An anticarcinogen (also known as a carcinopreventive agent) is a substance that counteracts the effects of a carcinogen or inhibits the development of cancer. Anticarcinogens are different from anticarcinoma agents (also known as anticancer or an ...

agents

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical canc ...

and

omacetaxine mepesuccinate Omacetaxine mepesuccinate ( INN, trade names Synribo ), formerly named as homoharringtonine or HHT, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML). HHT is a natural plant alkaloid derived fro ...

(from ''

Taxus brevifolia ''Taxus brevifolia'', the Pacific yew or western yew, is a species of tree in the yew family Taxaceae native to the Pacific Northwest of North America. It is a small evergreen conifer, thriving in moisture and otherwise tending to take the form ...

'' and '' Cephalotaxus harringtonii'', respectively), the

antimalarial Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young ...

agent

artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to '' Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her ...

(from ''

Artemisia annua ''Artemisia annua'', also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood (), is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North Am ...

''), and the

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and ...

galantamine Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid that has been isolated from the bulbs and flowers of '' Galanthus nivalis'' (Common snowd ...

(from '' Galanthus'' spp.), used to treat Alzheimer's disease. Other plant-derived drugs, used medicinally and/or recreationally include

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal le ...

tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or ...

muscarine Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms, particularly in '' Inocybe'' and '' Clitocybe'' species, such as the deadly '' C. dealbata''. Mushrooms in the genera '' Entoloma'' and ''Mycena'' have ...

, and

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

Animals

Animals also represent a source of bioactive natural products. In particular,

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...

ous animals such as snakes, spiders, scorpions, caterpillars, bees, wasps, centipedes, ants, toads, and frogs have attracted much attention. This is because venom constituents (peptides, enzymes, nucleotides, lipids, biogenic amines etc.) often have very specific interactions with a

macromolecular A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...

target in the body (e.g. α-bungarotoxin from cobras). As with plant feeding deterrents, this biological activity is attributed to natural selection, organisms capable of killing or paralyzing their prey and/or defending themselves against predators being more likely to survive and reproduce. Because of these specific chemical-target interactions, venom constituents have proved important tools for studying

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

, ion channels, and

s. In some cases, they have also served as leads in the development of novel drugs. For example, teprotide, a peptide isolated from the venom of the Brazilian pit viper ''

Bothrops jararaca ''Bothrops jararaca'' — known as the ''jararaca'' or ''yarara'' — is a highly venomous pit viper species endemic to South America in southern Brazil, Paraguay, and northern Argentina. The specific name, ''jararaca'', is derived from the Tup ...

'', was a lead in the development of the

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

agents

cilazapril Cilazapril is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and congestive heart failure. It was patented in 1982 and approved for medical use in 1990. Chemistry Of the eight possible stereo ...

and captopril. Also, echistatin, a

disintegrin Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Operation Disintegrins work by countering the bl ...

from the venom of the saw-scaled viper ''

Echis carinatus ''Echis carinatus'', known as the saw-scaled viper,Mallow D, Ludwig D, Nilson G (2003). ''True Vipers: Natural History and Toxinology of Old World Vipers''. Malabar, Florida: Krieger Publishing Company. 359 pp. . Indian saw-scaled viper, little I ...

'' was a lead in the development of the

antiplatelet drug An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effecti ...

tirofiban Tirofiban, sold under the brand name Aggrastat, is an antiplatelet medication. It belongs to a class of antiplatelets named glycoprotein IIb/IIIa inhibitors. Tirofiban is a small molecule inhibitor of the protein-protein interaction between fib ...

. In addition to the

terrestrial animal Terrestrial animals are animals that live predominantly or entirely on land (e.g. cats, dogs, ants, spiders), as compared with aquatic animals, which live predominantly or entirely in the water (e.g. fish, lobsters, octopuses), and amphibian ...

s and amphibians described above, many marine animals have been examined for pharmacologically active natural products, with

coral Corals are marine invertebrates within the class Anthozoa of the phylum Cnidaria. They typically form compact colonies of many identical individual polyps. Coral species include the important reef builders that inhabit tropical oceans and ...

s, sponges,

tunicate A tunicate is a marine invertebrate animal, a member of the subphylum Tunicata (). It is part of the Chordata, a phylum which includes all animals with dorsal nerve cords and notochords (including vertebrates). The subphylum was at one time ...

s, sea snails, and

bryozoa Bryozoa (also known as the Polyzoa, Ectoprocta or commonly as moss animals) are a phylum of simple, aquatic invertebrate animals, nearly all living in sedentary colonies. Typically about long, they have a special feeding structure called a ...

ns yielding chemicals with interesting analgesic,

antiviral Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...

, and

activities. Two examples developed for clinical use include ω-

conotoxin A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Cono ...

(from the marine snail ''

Conus magus ''Conus magus'', common name the magical cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. Like all species within the genus ''Conus'', these snails are predatory and venomous. ...

'') and ecteinascidin 743 (from the tunicate '' Ecteinascidia turbinata''). The former, ω-conotoxin, is used to relieve severe and chronic pain, while the latter, ecteinascidin 743 is used to treat

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

soft tissue sarcoma. Other natural products derived from marine animals and under investigation as possible therapies include the

antitumour Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

agents

discodermolide (+)-Discodermolide is a polyketide natural product found to stabilize microtubules. (+)-discodermolide was isolated by Gunasekera and his co-workers at the Harbor Branch Oceanographic Institute from the deep-sea sponge '' Discodermia dissoluta'' i ...

(from the sponge '' Discodermia dissoluta''), eleutherobin (from the coral '' Erythropodium caribaeorum''), and the bryostatins (from the bryozoan ''

Bugula neritina ''Bugula neritina'' ( commonly known as brown bryozoan or common bugula) is a cryptic species complex of sessile marine animal in the genus ''Bugula''.Gordon, D. (2015). Bugula neritina (Linnaeus, 1758). In: Bock, P.; Gordon, D. (2015) World Lis ...

'').

Medical uses

Natural products sometimes have pharmacological activity that can be of therapeutic benefit in treating diseases. Moreover, synthetic analogs of natural products with improved potency and safety can be prepared and therefore natural products are often used as starting points for drug discovery. Natural product constituents have inspired numerous drug discovery efforts that eventually gained approval as new drugs

Traditional medicine

Indigenous peoples Indigenous peoples are culturally distinct ethnic groups whose members are directly descended from the earliest known inhabitants of a particular geographic region and, to some extent, maintain the language and culture of those original people ...

and

ancient civilizations A civilization (or civilisation) is any complex society characterized by the development of a state, social stratification, urbanization, and symbolic systems of communication beyond natural spoken language (namely, a writing system). Civi ...

experimented with various plant and animal parts to determine what effect they might have. Through

trial and error Trial and error is a fundamental method of problem-solving characterized by repeated, varied attempts which are continued until success, or until the practicer stops trying. According to W.H. Thorpe, the term was devised by C. Lloyd Morgan (18 ...

in isolated cases,

traditional healer A folk healer is an unlicensed person who practices the art of healing using traditional practices, herbal remedies and the power of suggestion. The healer may be a highly trained person who pursues their specialties, learning by study, observa ...

s or

shamans Shamanism is a religious practice that involves a practitioner (shaman) interacting with what they believe to be a spirit world through altered states of consciousness, such as trance. The goal of this is usually to direct spirits or spiritu ...

found some sources to provide therapeutic effect, representing knowledge of a crude drug that was passed down through generations in such practices as

traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of acti ...

and

Ayurveda Ayurveda () is an alternative medicine system with historical roots in the Indian subcontinent. The theory and practice of Ayurveda is pseudoscientific. Ayurveda is heavily practiced in India and Nepal, where around 80% of the population rep ...

. Extracts of some natural products led to modern discovery of their active constituents and eventually to the development of new drugs.

Modern natural product-derived drugs

A large number of currently prescribed drugs have been either directly derived from or inspired by natural products. Some of the oldest natural product based drugs are analgesics. The bark of the

willow Willows, also called sallows and osiers, from the genus ''Salix'', comprise around 400 speciesMabberley, D.J. 1997. The Plant Book, Cambridge University Press #2: Cambridge. of typically deciduous trees and shrubs, found primarily on moist so ...

tree has been known from antiquity to have pain relieving properties. This is due to presence of the natural product

salicin Salicin is an alcoholic β- glucoside. Salicin is produced in (and named after) willow (''Salix'') bark. It is a biosynthetic precursor to salicylaldehyde. Medicinal aspects Salicin is found in the bark of and leaves of willows, poplars and v ...

which in turn may be hydrolyzed into salicylic acid. A synthetic derivative

acetylsalicylic acid Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat ...

better known as aspirin is a widely used pain reliever. Its mechanism of action is inhibition of the

cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as pr ...

(COX) enzyme. Another notable example is opium is extracted from the latex from ''Papaver somniferous'' (a flowering poppy plant). The most potent narcotic component of opium is the alkaloid

which acts as an

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...

agonist. A more recent example is the

N-type calcium channel N-type calcium channels also called Cav2.2 channels are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the prima ...

blocker

ziconotide Ziconotide (SNX–111; Prialt), also called intrathecal ziconotide (ITZ) because of its administration route, is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from ''Conus magus'', a cone snail, it is the ...

analgesic which is based on a cyclic peptide cone snail toxin (ω-

MVIIA) from the species ''

''. A significant number of

anti-infectives An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...

are based on natural products. The first antibiotic to be discovered, penicillin, was isolated from the mold ''

Penicillium ''Penicillium'' () is a genus of ascomycetous fungi that is part of the mycobiome of many species and is of major importance in the natural environment, in food spoilage, and in food and drug production. Some members of the genus produce pe ...

''. Penicillin and related

beta lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...

s work by inhibiting DD-transpeptidase enzyme that is required by bacteria to cross link

to form the cell wall. Several natural product drugs target

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...

, which is a component of the

. These include the tubulin polymerization inhibitor

colchicine Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken b ...

isolated from the ''

Colchicum autumnale ''Colchicum autumnale'', commonly known as autumn crocus, meadow saffron, or naked ladies, is a toxic autumn-blooming flowering plant that resembles the true crocuses, but is a member of the plant family Colchicaceae, unlike the true crocuses, whi ...

'' (autumn crocus flowering plant), which is used to treat

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...

. Colchicine is biosynthesized from the amino acids phenylalanine and

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

Paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical canc ...

, in contrast, is a tubulin polymerization stabilizer and is used as a

chemotherapeutic Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...

drug. Paclitaxel is based on the terpenoid natural product

taxol Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical ca ...

, which is isolated from ''

'' (the pacific yew tree). A class of drugs widely used to lower cholesterol are the HMG-CoA reductase inhibitors, for example

atorvastatin Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth. Common ...

. These were developed from

mevastatin Mevastatin (compactin, ML-236B) is a hypolipidemic agent that belongs to the statins class. It was isolated from the mold ''Penicillium citrinum'' by Akira Endo in the 1970s, and he identified it as a HMG-CoA reductase inhibitor, i.e., a statin. ...

, a polyketide produced by the fungus ''Penicillium citrinum''. Finally, a number natural product drugs are used to treat hypertension and congestive heart failure. These include the angiotensin-converting enzyme inhibitor captopril. Captopril is based on the peptidic bradykinin potentiating factor isolated from venom of the Brazilian arrowhead viper (''

'').

Limiting and enabling factors

Numerous challenges limit the use of natural products for drug discovery, resulting in 21st century preference by pharmaceutical companies to dedicate discovery efforts toward

high-throughput screening High-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling ...

of pure synthetic compounds with shorter timelines to refinement. Natural product sources are often unreliable to access and supply, have a high probability of duplication, inherently create intellectual property concerns about patent protection, vary in composition due to sourcing season or environment, and are susceptible to rising

rates. The biological resource for drug discovery from natural products remains abundant, with small percentages of microorganisms, plant species, and insects assessed for bioactivity. In enormous numbers, bacteria and marine microorganisms remain unexamined. As of 2008, the field of

metagenomics Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microb ...

was proposed to examine genes and their function in soil microbes, but most pharmaceutical firms have not exploited this resource fully, choosing instead to develop "diversity-oriented synthesis" from libraries of known drugs or natural sources for lead compounds with higher potential for bioactivity.

Isolation and purification

All natural products begin as mixtures with other compounds from the natural source, often very complex mixtures, from which the product of interest must be isolated and purified. The ''isolation'' of a natural product refers, depending on context, either to the isolation of sufficient quantities of pure chemical matter for chemical structure elucidation, derivitzation/degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but historically, often more), or to the isolation of "analytical quantities" of the substance of interest, where the focus is on identification and quantitation of the substance (e.g. in biological tissue or fluid), and where the quantity isolated depends on the analytical method applied (but is generally always sub-microgram in scale). The ease with which the active agent can be isolated and purified depends on the structure, stability, and quantity of the natural product. The methods of isolation applied toward achieving these two distinct scales of product are likewise distinct, but generally involve extraction, precipitation, adsorptions,

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system ( ...

, and sometimes crystallizations. In both cases, the isolated substance is purified to ''chemical homogeneity'', i.e. specific combined separation and analytical methods such as LC-MS methods are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—with the goal being repeated detection of only a single species present in the putative pure sample. Early isolation is almost inevitably followed by ''structure determination'', especially if an important pharmacologic activity is associated with the purified natural product. Structure determination refers to methods applied to determine the

of an isolated, pure natural product, a process that involves an array of chemical and physical methods that have changed markedly over the history of natural products research; in earliest days, these focused on chemical transformation of unknown substances into known substances, and measurement of physical properties such as melting point and boiling point, and related methods for determining molecular weight. In the modern era, methods focus on mass spectrometry and nuclear magnetic resonance methods, often multidimensional, and, when feasible, small molecule crystallography. For instance, the

of penicillin was determined by

Dorothy Crowfoot Hodgkin Dorothy Mary Crowfoot Hodgkin (née Crowfoot; 12 May 1910 – 29 July 1994) was a Nobel Prize-winning British chemist who advanced the technique of X-ray crystallography to determine the structure of biomolecules, which became essential fo ...

in 1945, work for which she later received a Nobel Prize in Chemistry (1964).

Synthesis

Many natural products have very complex

structures A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

. The perceived complexity of a natural product is a qualitative matter, consisting of consideration of its molecular mass, the particular arrangements of substructures (

functional groups In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

, rings etc.) with respect to one another, the number and density of those functional groups, the stability of those groups and of the molecule as a whole, the number and type of stereochemical elements, the physical properties of the molecule and its intermediates (which bear on the ease of its handling and purification), all of these viewed in the context of the novelty of the structure and whether preceding related synthetic efforts have been successful (see below for details). Some natural products, especially those less complex, are easily and cost-effectively prepared via complete chemical synthesis from readily available, simpler chemical ingredients, a process referred to as

(especially when the process involves no steps mediated by biological agents). Not all natural products are amenable to total synthesis, cost-effective or otherwise. In particular, those most complex often are not. Many are accessible, but the required routes are simply too expensive to allow synthesis on any practical or industrial scale. However, to be available for further study, all natural products must yield to isolation and purification. This may suffice if isolation provides appropriate quantities of the natural product for the intended purpose (e.g. as a drug to alleviate disease). Drugs such as penicillin,

, and

proved to be affordably acquired at needed commercial scales solely via isolation procedures (without any significant synthetic chemistry contributing). However, in other cases, needed agents are not available without synthetic chemistry manipulations.

Semisynthesis

The process of isolating a natural product from its source can be costly in terms of committed time and material expense, and it may challenge the availability of the relied upon natural resource (or have ecological consequences for the resource). For instance, it has been estimated that the bark of an entire

yew tree Yew is a common name given to various species of trees. It is most prominently given to any of various coniferous trees and shrubs in the genus ''Taxus'': * European yew or common yew (''Taxus baccata'') * Pacific yew or western yew (''Taxus b ...

(''Taxus brevifolia'') would have to be harvested to extract enough

for just a single dose of therapy. Furthermore, the number of

structural analog A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...

ues obtainable for structure–activity analysis (SAR) simply via harvest (if more than one structural analogue is even present) is limited by the biology at work in the organism, and so outside of the experimentalist's control. In such cases where the ultimate target is harder to come by, or limits SAR, it is sometimes possible to source a middle-to-late stage biosynthetic precursor or analogue from which the ultimate target can be prepared. This is termed

or ''partial synthesis''. With this approach, the related biosynthetic intermediate is harvested and then converted to the final product by conventional procedures of

. This strategy can have two advantages. Firstly, the intermediate may be more easily extracted, and in higher yield, than the ultimate desired product. An example of this is paclitaxel, which can be manufactured by extracting

10-deacetylbaccatin III 10-Deacetylbaccatins are a series of closely related natural organic compounds isolated from the yew tree (Genera ''Taxus''). 10-Deacetylbaccatin III is a precursor to the anti-cancer drug docetaxel (Taxotere). 10-deacetylbaccatin III 10-''O'' ...

from ''T. brevifolia'' needles, then carrying out a four-step synthesis. Secondly, the route designed between semisynthetic starting material and ultimate product may permit analogues of the final product to be synthesized. The newer generation semisynthetic

penicillins Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

are an illustration of the benefit of this approach.

Total synthesis

In general, the

of natural products is a non-commercial research activity, aimed at deeper understanding of the synthesis of particular natural product frameworks, and the development of fundamental new synthetic methods. Even so, it is of tremendous commercial and societal importance. By providing challenging synthetic targets, for example, it has played a central role in the development of the field of

. Prior to the development of

analytical chemistry Analytical chemistry studies and uses instruments and methods to separate, identify, and quantify matter. In practice, separation, identification or quantification may constitute the entire analysis or be combined with another method. Separati ...

methods in the twentieth century, the structures of natural products were affirmed by total synthesis (so-called "structure proof by synthesis"). Early efforts in natural products synthesis targeted complex substances such as

cobalamin Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...

(vitamin B₁₂), an essential cofactor in cellular

Symmetry

Examination of dimerized and trimerized natural products has shown that an element of bilateral symmetry is often present. Bilateral symmetry refers to a molecule or system that contains a C₂, C_s, or C_2v point group identity. C₂ symmetry tends to be much more abundant than other types of bilateral symmetry. This finding sheds light on how these compounds might be mechanistically created, as well as providing insight into the thermodynamic properties that make these compounds more favorable. Density functional theoretical (DFT), Hartree Fock, and semiempirical calculations also show some favorability for dimerization in natural products due to evolution of more energy per bond than the equivalent trimer or tetramer. This is proposed to be due to

steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

at the core of the molecule, as most natural products dimerize and trimerize in a head-to-head fashion rather than head-to-tail.

Research and teaching

Research and teaching activities related to natural products fall into a number of diverse academic areas, including

, pharmacognosy, ethnobotany,

traditional medicine Traditional medicine (also known as indigenous medicine or folk medicine) comprises medical aspects of traditional knowledge that developed over generations within the folk beliefs of various societies, including indigenous peoples, before the ...

, and ethnopharmacology. Other biological areas include chemical biology,

chemical ecology A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wit ...

chemogenomics Chemogenomics, or chemical genomics, is the systematic screening of targeted chemical libraries of small molecules against individual drug target families (e.g., GPCRs, nuclear receptors, kinases, proteases, etc.) with the ultimate goal of id ...

, systems biology,

molecular modeling Molecular modelling encompasses all methods, theoretical and computational, used to model or mimic the behaviour of molecules. The methods are used in the fields of computational chemistry, drug design, computational biology and materials scien ...

chemometrics Chemometrics is the science of extracting information from chemical systems by data-driven means. Chemometrics is inherently interdisciplinary, using methods frequently employed in core data-analytic disciplines such as multivariate statistics, a ...

, and chemoinformatics.

Chemistry

Natural products chemistry is a distinct area of chemical research which was important in the development and history of chemistry. Isolating and identifying natural products has been important to source substances for early preclinical drug discovery research, to understand

and ethnopharmacology, and to find pharmacologically useful areas of

chemical space Chemical space is a concept in cheminformatics referring to the property space spanned by all possible molecules and chemical compounds adhering to a given set of construction principles and boundary conditions. It contains millions of compounds w ...

. To achieve this, many technological advances have been made, such as the evolution of technology associated with chemical separations, and the development of modern methods in chemical structure determination such as

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...

. Early attempts to understand the biosynthesis of natural products, saw chemists employ first radiolabelling and more recently stable isotope labeling combined with NMR experiments. In addition, natural products are prepared by organic synthesis, to provide confirmation of their structure, or to give access to larger quantities of natural products of interest. In this process, the structure of some natural products have been revised, and the challenge of synthesising natural products has led to the development of new synthetic methodology, synthetic strategy, and tactics. In this regard, natural products play a central role in the training of new synthetic organic chemists, and are a principal motivation in the development of new variants of old chemical reactions (e.g., the Evans aldol reaction), as well as the discovery of completely new chemical reactions (e.g., the

Woodward cis-hydroxylation The Woodward cis-hydroxylation (also known as the Woodward reaction) is the chemical reaction of alkenes with iodine and silver acetate in wet acetic acid to form cis-diols. Woodward, R. B., (conversion of olefin into cis-diol) The reaction is n ...

Sharpless epoxidation The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols. The oxidizing agent is ''tert''-butyl hydroperoxide. The method relies on a catalyst formed fro ...

, and Suzuki–Miyaura cross-coupling reactions).

History

Foundations of organic and natural product chemistry

The concept of natural products dates back to the early 19th century, when the foundations of

were laid. Organic chemistry was regarded at that time as the chemistry of substances that plants and animals are composed of. It was a relatively complex form of chemistry and stood in stark contrast to inorganic chemistry, the principles of which had been established in 1789 by the Frenchman

Antoine Lavoisier Antoine-Laurent de Lavoisier ( , ; ; 26 August 17438 May 1794),
CNRS (

Traité Élémentaire de Chimie ''Traité élémentaire de chimie'' (''Elementary Treatise on Chemistry'') is a textbook written by Antoine Lavoisier published in 1789 and translated into English by Robert Kerr in 1790 under the title ''Elements of Chemistry in a New Systemati ...

''.

Isolation

Lavoisier showed at the end of the 18th century that organic substances consisted of a limited number of elements: primarily carbon and hydrogen and supplemented by oxygen and nitrogen. He quickly focused on the isolation of these substances, often because they had an interesting pharmacological activity. Plants were the main source of such compounds, especially alkaloids and

glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycoside ...

s. It was long been known that opium, a sticky mixture of alkaloids (including codeine,

noscapine Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae ( ...

thebaine Thebaine (paramorphine), also known as codeine methyl enol ether, is an opiate alkaloid, its name coming from the Greek Θῆβαι, '' Thēbai'' (Thebes), an ancient city in Upper Egypt. A minor constituent of opium, thebaine is chemically similar ...

, and

papaverine Papaverine (Latin '' papaver'', "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of e ...

) from the opium poppy (

Papaver somniferum ''Papaver somniferum'', commonly known as the opium poppy or breadseed poppy, is a species of flowering plant in the family Papaveraceae. It is the species of plant from which both opium and poppy seeds are derived and is also a valuable orname ...

), possessed a narcotic and at the same time mind-altering properties. By 1805, morphine had already been isolated by the German chemist

Friedrich Sertürner Friedrich Wilhelm Adam Sertürner (19 June 1783 – 20 February 1841) was a German pharmacist and a pioneer of alkaloid chemistry. He is best known for his discovery of morphine in 1804. Biography Friedrich Wilhelm Adam Sertürner was born to J ...

and in the 1870s it was discovered that boiling morphine with acetic anhydride produced a substance with a strong pain suppressive effect: heroin. In 1815, Eugène Chevreul isolated

, a crystalline substance, from animal tissue that belongs to the class of steroids, and in 1819 strychnine, an alkaloid was isolated.

Synthesis

A second important step was the synthesis of organic compounds. Whereas the synthesis of inorganic substances had been known for a long time, the synthesis of organic substances was a difficult hurdle. In 1827 the Swedish chemist Jöns Jacob Berzelius held that an indispensable force of nature for the synthesis of organic compounds, called vital force or life force, was needed. This philosophical idea,

vitalism Vitalism is a belief that starts from the premise that "living organisms are fundamentally different from non-living entities because they contain some non-physical element or are governed by different principles than are inanimate things." Wher ...

, well into the 19th century had many supporters, even after the introduction of the

atomic theory Atomic theory is the scientific theory that matter is composed of particles called atoms. Atomic theory traces its origins to an ancient philosophical tradition known as atomism. According to this idea, if one were to take a lump of matter ...

. The idea of vitalism especially fitted in with beliefs in medicine; the most traditional healing practices believed that disease was the result of some imbalance in the vital energies that distinguishes life from nonlife. A first attempt to break the vitalism idea in science was made in 1828, when the German chemist Friedrich Wöhler succeeded in synthesizing

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...

, a natural product found in

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

, by heating

ammonium cyanate Ammonium cyanate is an inorganic compound with the formula . It is a colorless, solid salt. Structure and reactions The structure of this salt was verified by X-ray crystallography. The respective C–O and C–N distances are 1.174(8) and 1.1 ...

, an inorganic substance: :

\mathrm

This reaction showed that there was no need for a life force in order to prepare organic substances. This idea, however, was initially met with a high degree of skepticism, and only 20 years later, with the synthesis of acetic acid from carbon by

Adolph Wilhelm Hermann Kolbe Adolph Wilhelm Hermann Kolbe (27 September 1818 – 25 November 1884) was a major contributor to the birth of modern organic chemistry. He was a professor at Marburg and Leipzig. Kolbe was the first to apply the term synthesis in a chemical con ...

, was the idea accepted. Organic chemistry has since developed into an independent area of research dedicated to the study of carbon-containing compounds, since that element in common was detected in a variety of nature-derived substances. An important factor in the characterization of organic materials was on the basis of their physical properties (such as melting point, boiling point, solubility, crystallinity, or color).

Structural theories

A third step was the structure elucidation of organic substances: although the elemental composition of pure organic substances (irrespective of whether they were of natural or synthetic origin) could be determined fairly accurately, the molecular structure was still a problem. The urge to do structural elucidation resulted from a dispute between Friedrich Wöhler and Justus von Liebig, who both studied a silver salt of the same composition but had different properties. Wöhler studied

silver cyanate Silver cyanate is the cyanate salt of silver Silver is a chemical element with the symbol Ag (from the Latin ', derived from the Proto-Indo-European ''h₂erǵ'': "shiny" or "white") and atomic number 47. A soft, white, lustrous transit ...

, a harmless substance, while von Liebig investigated

silver fulminate Silver fulminate (AgCNO) is the highly explosive silver salt of fulminic acid. Silver fulminate is a primary explosive, but has limited use as such due to its extreme sensitivity to impact, heat, pressure, and electricity. The compound becomes pr ...

, a salt with explosive properties. The elemental analysis shows that both salts contain equal quantities of silver, carbon, oxygen and nitrogen. According to the then prevailing ideas, both substances should possess the same properties, but this was not the case. This apparent contradiction was later solved by Berzelius's theory of isomers, whereby not only the number and type of elements are of importance to the properties and chemical reactivity, but also the position of atoms in within a compound. This was a direct cause for the development of structure theories, such as the

radical theory Radical theory is an obsolete scientific theory in chemistry describing the structure of organic compounds. The theory was pioneered by Justus von Liebig, Friedrich Wöhler and Auguste Laurent around 1830 and is not related to the modern understand ...

of Jean-Baptiste Dumas and the substitution theory of Auguste Laurent. However, it took until 1858 before by

August Kekulé Friedrich August Kekulé, later Friedrich August Kekule von Stradonitz ( , ; 7 September 1829 – 13 July 1896), was a German organic chemist. From the 1850s until his death, Kekulé was one of the most prominent chemists in Europe, especially ...

formulated a definite structure theory. He posited that carbon is tetravalent and can bind to itself to form carbon chains as they occur in natural products.

Expanding the concept

The concept of natural product, which initially based on organic compounds that could be isolated from plants, was extended to include animal material in the middle of the 19th century by the German Justus von Liebig.

Hermann Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of dra ...

in 1884, turned his attention to the study of carbohydrates and purines, work for which he was awarded the Nobel Prize in 1902. He also succeeded to make synthetically in the laboratory in a variety of carbohydrates, including

and

mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...

. After the discovery of penicillin by Alexander Fleming in 1928, fungi and other micro-organisms were added to the arsenal of sources of natural products.

Milestones

By the 1930s, several large classes of natural products were known. Important milestones included: *

Terpene Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ...

s, first systematically studied by

Otto Wallach Otto Wallach (; 27 March 1847 – 26 February 1931) was a German chemist and recipient of the 1910 Nobel Prize in Chemistry for his work on alicyclic compounds. Biography Wallach was born in Königsberg, the son of a Prussian civil servant. Hi ...

(Nobel Prize 1910) and later by

Leopold Ružička Leopold Ružička (; born Lavoslav Stjepan Ružička; 13 September 1887 – 26 September 1976) was a Croatian-Swiss scientist and joint winner of the 1939 Nobel Prize in Chemistry "for his work on polymethylenes and higher terpenes" "including t ...

(Nobel Prize 1939) * Dyes based on

porphin Porphine or porphin is an organic chemical compound with formula . The molecule, which is flat, consists of four pyrrole-like rings joined by four methine (= C H−) groups to form a larger macrocycle ring, which makes it the simplest of the tet ...

s (including chlorophyll and

heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...

), studied by

Richard Willstätter Richard Martin Willstätter FRS(For) HFRSE (, 13 August 1872 – 3 August 1942) was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry. Willstätter invente ...

(Nobel Prize 1915) and Hans Fischer (Nobel Prize 1930) * Steroids, studied by

Heinrich Otto Wieland Heinrich Otto Wieland (; 4 June 1877 – 5 August 1957) was a German chemist. He won the 1927 Nobel Prize in Chemistry for his research into the bile acids. Career In 1901 Wieland received his doctorate at the University of Munich while studyi ...

(Nobel Prize 1927) and

Adolf Windaus Adolf Otto Reinhold Windaus (; 25 December 1876 – 9 June 1959) was a German chemist who won a Nobel Prize in Chemistry in 1928 for his work on sterols and their relation to vitamins. He was the doctoral advisor of Adolf Butenandt who also won ...

(Nobel Prize 1928) * Carotenoids, studied by

Paul Karrer Paul may refer to: *Paul (given name), a given name (includes a list of people with that name) * Paul (surname), a list of people People Christianity *Paul the Apostle (AD c.5–c.64/65), also known as Saul of Tarsus or Saint Paul, early Chri ...

(Nobel Prize 1937) *

Vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...

s, studied among others by

, Adolf Windaus, Robert R. Williams,

Norman Haworth Sir Walter Norman Haworth FRS (19 March 1883 – 19 March 1950) was a British chemist best known for his groundbreaking work on ascorbic acid ( vitamin C) while working at the University of Birmingham. He received the 1937 Nobel Prize in Chem ...

(Nobel Prize 1937),

Richard Kuhn Richard Johann Kuhn (; 3 December 1900 – 1 August 1967) was an Austrian-German biochemist who was awarded the Nobel Prize in Chemistry in 1938 "for his work on carotenoids and vitamins". Biography Early life Kuhn was born in Vienna, Austr ...

(Nobel Prize 1938) and

Albert Szent-Györgyi Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...

Hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

s studied by

Adolf Butenandt Adolf Friedrich Johann Butenandt (; 24 March 1903 – 18 January 1995) was a German biochemist. He was awarded the Nobel Prize in Chemistry in 1939 for his "work on sex hormones." He initially rejected the award in accordance with government po ...

(Nobel Prize 1939) and Edward Calvin Kendall (Nobel Prize 1950) * Alkaloids and anthocyanins, studied by, among others, Robert Robinson (Nobel Prize 1947)

References

External links

* * * {{Authority control Natural products Chemistry Nature

Classes

Function

Primary metabolites

Secondary metabolites

Biosynthesis

Carbohydrates

Fatty acids and polyketides

Sources

Prokaryotic

Bacteria

Archaea

Eukaryotic

Fungi

Plants

Animals

Medical uses

Traditional medicine

Modern natural product-derived drugs

Limiting and enabling factors

Isolation and purification

Synthesis

Semisynthesis

Total synthesis

Symmetry

Research and teaching

Chemistry

History

Foundations of organic and natural product chemistry

Isolation

Synthesis

Structural theories

Expanding the concept

Milestones

See also

Journals

References

Further reading

External links