Semisynthesis
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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 distinct chemical and medicinal properties. The novel compounds generally have a high molecular weight or a complex molecular structure, more so than those produced by total synthesis from simple starting materials. Semisynthesis is a means of preparing many medicines more cheaply than by total synthesis since fewer chemical steps are necessary. Overview Drugs derived from natural sources are usually produced by isolation from the natural source or, as described here, by semisynthesis from such an isolated agent. From the viewpoint of chemical synthesis, living organisms are remarkable chemical factories that can easily produce structurally-complex chemical compounds by biosynthesis. In contrast, engineered chemical synthesis is necessar ...
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Natural Source
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis (both semisynthesis and total synthesis) and have played a central role in the development of the field of organic chemistry 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 organic chemistry, the definition of natural products is usually restricted to organic compounds isolated from natural sources that are produced by the pathways of primary or secondary metabolism. Within the field of medicinal chemistry, the definition is often further restricted to secondary metabolites. Secondary metabolites (or specialized metabolites ...
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Paclitaxel Total Synthesis
Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harvested from a scarce resource, namely the Pacific yew (''Taxus brevifolia''). Not only is the synthetic reproduction of the compound itself of great commercial and scientific importance, but it also opens the way to paclitaxel derivatives not found in nature but with greater potential. The paclitaxel molecule consists of a tetracyclic core called baccatin III and an amide tail. The core rings are conveniently called (from left to right) ring A (a cyclohexene), ring B (a cyclooctane), ring C (a cyclohexane) and ring D (an oxetane). The paclitaxel drug development process took over 40 years. The anti-tumor activity of a bark extract of the Pacific yew tree was discovered in 1963 as a follow up of a US government plant screening program already in ...
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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 discovery. Artemisinin-based combination therapies (ACTs) are now standard treatment worldwide for ''P. falciparum'' malaria as well as malaria due to other species of ''Plasmodium''. Artemisinin is extracted from the plant ''Artemisia annua'', sweet wormwood, a herb employed in Chinese traditional medicine. A precursor compound can be produced using a genetically engineered yeast, which is much more efficient than using the plant. Artemisinin and its derivatives are all sesquiterpene lactones containing an unusual peroxide bridge. This endoperoxide 1,2,4-trioxane ring is responsible for their antimalarial properties. Few other natural compounds with such a peroxide bridge are known. Artemisinin and its derivatives have been used for the t ...
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Fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from the other eukaryotic kingdoms, which by one traditional classification include Plantae, Animalia, Protozoa, and Chromista. A characteristic that places fungi in a different kingdom from plants, bacteria, and some protists is chitin in their cell walls. Fungi, like animals, are heterotrophs; they acquire their food by absorbing dissolved molecules, typically by secreting digestive enzymes into their environment. Fungi do not photosynthesize. Growth is their means of mobility, except for spores (a few of which are flagellated), which may travel through the air or water. Fungi are the principal decomposers in ecological systems. These and other differences place fungi in a single group of related organisms, named the ''Eumycota'' (''t ...
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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 it from semisynthesis. Syntheses may sometimes conclude at a precursor with further known synthetic pathways to a target molecule, in which case it is known as a formal synthesis. Total synthesis target molecules can be natural products, medicinally-important active ingredients, known intermediates, or molecules of theoretical interest. Total synthesis targets can also be organometallic or inorganic, though these are rarely encountered. Total synthesis projects often require a wide diversity of reactions and reagents, and subsequently requires broad chemical knowledge and training to be successful. Often, the aim is to discover a new route of synthesis for a target molecule for which there already exist known routes. Sometimes, however, no ...
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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 modern laboratory uses, the process is reproducible and reliable. A chemical synthesis involves one or more compounds (known as '' reagents'' or ''reactants'') that will experience a transformation when subjected to certain conditions. Various reaction types can be applied to formulate a desired product. This requires mixing the compounds in a reaction vessel, such as a chemical reactor or a simple round-bottom flask. Many reactions require some form of processing (" work-up") or purification procedure to isolate the final product. The amount produced by chemical synthesis is known as the ''reaction yield''. Typically, yields are expressed as a mass in grams (in a laboratory setting) or as a percentage of the total theoretical quantity that ...
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Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via routes other than intravenous, its bioavailability is generally lower than that of intravenous due to intestinal endothelium absorption and first-pass metabolism. Thereby, mathematically, bioavailability equals the ratio of comparing the area under the plasma drug concentration curve versus time (AUC) for the extravascular formulation to the AUC for the intravascular formulation. AUC is used because AUC is proportional to the dose that has entered the systemic circulation. Bioavailability of a drug is an average value; to take population variability into account, deviation range is shown as ±. To ensure that the drug taker who has poor absorption is dosed appropriately, the bottom value o ...
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Chlortetracycline
Chlortetracycline (trade name Aureomycin, Lederle Laboratories) is a tetracycline antibiotic, the first tetracycline to be identified. It was discovered in 1945 at Lederle Laboratories under the supervision of scientist Yellapragada Subbarow and Benjamin Minge Duggar. Duggar identified the antibiotic as the product of an actinomycete he cultured from a soil sample collected from Sanborn Field at the University of Missouri. The organism was named ''Streptomyces aureofaciens'' and the isolated drug, Aureomycin, because of their golden color. It is on the World Health Organization's List of Essential Medicines. Medical uses A combination cream with triamcinolone acetonide is available for the treatment of infected allergic dermatitis in humans. In veterinary medicine, chlortetracycline is commonly used to treat conjunctivitis in cats, dogs and horses. It is also used to treat infected wounds in cattle, sheep and pigs, and respiratory tract infections in calves, pigs and chickens. ...
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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 vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and syphilis. Common side effects include vomiting, diarrhea, rash, and loss of appetite. Other side effects include poor tooth development if used by children less than eight years of age, kidney problems, and sunburning easily. Use during pregnancy may harm the baby. It works by inhibiting protein synthesis in bacteria. Tetracycline was patented in 1953 and came into commercial use in 1978. It is on the World Health Organization's List of Essential Medicines. Tetracycline is available as a generic medication. Tetracycline was originally made from bacteria of the genus ''Streptomyces''. Medical uses Spectrum of activity Tetracyclines have a broad spectrum of antibiotic action. Originally, they possessed some level of bacteriostatic acti ...
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Tigecycline
Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as ''Staphylococcus aureus'', ''Acinetobacter baumannii'', and ''E. coli''. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance. It was given a U.S. Food and Drug Administration (FDA) fast-track approval and was approved on 17 June 2005. It was approved for medical use in the European Union in April 2006. It was removed from the World Health Organization's List of Essential Medicines in 2019. The World Health Organization classifies tigecycline as critically important for human medicine. Medical uses Antibacterial use Tigecycline is used to treat different kinds of ba ...
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Ergotamine
Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor. It is used Pharmacology, medicinally for treatment of acute migraine attacks (sometimes in combination with caffeine). Medicinal usage of ergot fungus began in the 16th century to induce childbirth, yet dosage uncertainties discouraged the use. It has been used to prevent post-partum hemorrhage (bleeding after childbirth). It was first isolated from the ergot, ergot fungus by Arthur Stoll at Sandoz in 1918 and marketed as Gynergen in 1921. Biosynthesis Ergotamine is a secondary metabolite (natural product) and the principal alkaloid produced by the ergot fungus, ''Claviceps purpurea'', and related fungi in the family Clavicipitaceae. Its biosynthesis in ...
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Taxus Baccata
''Taxus baccata'' is a species of evergreen tree in the family Taxaceae, native to western, central and southern Europe (including Britain and Ireland), northwest Africa, northern Iran, and southwest Asia.Rushforth, K. (1999). ''Trees of Britain and Europe''. Collins . It is the tree originally known as yew, though with other related trees becoming known, it may now be known as common yew, English yew, or European yew. It is primarily grown as an ornamental. Most parts of the plant are poisonous, with toxins that can be absorbed through inhalation and through the skin; consumption of even a small amount of the foliage can result in death. Taxonomy and naming The word ''yew'' is from Proto-Germanic ''*īwa-'', possibly originally a loanword from Gaulish ''*ivos'', compare Breton ''ivin,'' Irish '' ēo'', Welsh ''ywen'', French '' if'' (see Eihwaz for a discussion). In German it is known as ''Eibe''. ''Baccata'' is Latin for ''bearing berries''. The word ''yew'' as it was originally ...
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