Betaenone B, like other betaenones ( A and C), is a

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 norm ...

isolated from the

fungus 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 th ...

Pleospora betae ''Pleospora betae'' is a plant pathogen infecting beet. It contains the chemical substances betaenone A, B and C. Pleospora betae develops on dead beet residues and is a marsupial stage of the Phoma betae anamorph, parasitizing on beets and ca ...

'', a plant pathogen. Its

phytotoxic Phytotoxins are substances that are poisonous or toxic to the growth of plants. Phytotoxic substances may result from human activity, as with herbicides, or they may be produced by plants, by microorganisms, or by naturally occurring chemical react ...

properties have been shown to cause

sugar beet A sugar beet is a plant whose root contains a high concentration of sucrose and which is grown commercially for sugar production. In plant breeding, it is known as the Altissima cultivar group of the common beet (''Beta vulgaris''). Together wi ...

leaf spot A leaf spot is a limited, discoloured, diseased area of a leaf that is caused by fungal, bacterial or viral plant diseases, or by injuries from nematodes, insects, environmental factors, toxicity or herbicides. These discoloured spots or lesions ...

s, which is characterized by black,

pycnidia A pycnidium (plural pycnidia) is an asexual fruiting body produced by mitosporic fungi, for instance in the order Sphaeropsidales ( Deuteromycota, Coelomycetes) or order Pleosporales (Ascomycota, Dothideomycetes). It is often spherical or inve ...

containing,

concentric circle In geometry, two or more objects are said to be concentric, coaxal, or coaxial when they share the same center or axis. Circles, regular polygons and regular polyhedra, and spheres may be concentric to one another (sharing the same center point ...

s eventually leading to

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

of the leaf tissue. Of the seven phytotoxins isolated in fungal leaf spots from

(''Beta vulgaris''), betaenone B showed the least amount of phytotoxicity showing only 8% inhibition of growth while betaenone A and C showed 73% and 89%

growth inhibition ''Growth inhibition'' (GI) is a medical term pertaining to cancer therapy and the specific reduction in growth of tumors and oncogene cells by a chemical compound, mechanical therapy (e.g. electroporation), radiation, gene therapy, protein therapy, ...

, respectively. Betaenone B is therefore not considered toxic to the plant, but will produce leaf spots when present in high concentrations (0.33 μg/μL). While the mechanism of action of betaenone B has yet to be elucidated, betaenone C has been shown to inhibit

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

and

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

. Most of the major work on betaenone B, including the initial structure elucidation of betaenone A, B and C as well as the partial elucidation mechanism of

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

, was presented in three short papers published between 1983 and 1988. The compounds were found to inhibit a variety of

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

s signifying a possible role in

cancer treatment Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...

The structure of betaenone B was determined via

nuclear magnetic resonance spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...

(NMR), CD and

optical rotatory dispersion Optical rotatory dispersion is the variation in the optical rotation of a substance with a change in the wavelength of light. Optical rotatory dispersion can be used to find the absolute configuration of metal complexes. For example, when plane-pol ...

(ORD) measurements. While it was also shown that betaenone B could be converted to betaenone A by

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

by PCC followed by exposure to base, it wasn't until 1988 that a semi-complete total synthesis was reported. Using

1,3-butadiene 1,3-Butadiene () is the organic compound with the formula (CH2=CH)2. It is a colorless gas that is easily condensed to a liquid. It is important industrially as a precursor to synthetic rubber. The molecule can be viewed as the union of two viny ...

as a starting material, a

stereoselective In chemistry, stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non-stereospecific creation of a new stereocenter or during a non-stereospecific transformation of ...

synthesis of (+/-)-4-de(3'-hydroxypropionyl) betanenone B was achieved in a 24-step synthesis.

Bioactivity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ph ...

of this synthetic product was not tested and no further work on total synthesis of betaenones has been published since. While a complete ''de novo'' synthesis of betaenone B has yet to be reported, Daniel Pratt and Paul Hopkins in 1988 proposed a method for synthesizing a precursor of betaenone B from methoxybenzoquinone and 1,3-butadiene via a

Diels–Alder reaction In organic chemistry, the Diels–Alder reaction is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene derivative. It is the prototypical example of a peric ...

and Claisen chemistry.

Biosynthesis

Very little work has been done to elucidate the biosynthetic pathways of betaenones with almost no literature references published on the subject since 1988. Their low phytotoxicity and lack of biological significance in

human physiology The human body is the structure of a human being. It is composed of many different types of cells that together create tissues and subsequently organ systems. They ensure homeostasis and the viability of the human body. It comprises a head ...

has provoked a fairly small amount of interest in these compounds. The backbone carbon units of betaenone B are known to be synthesized via the

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 ...

synthesis (PKS) pathway. The backbone is synthesized through the addition of two carbon units via addition of

acetate An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

units from

acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

. The 5 methyl groups are added via

S-adenosyl methionine ''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...

(SAM)

methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...

, as opposed to incorporation of

propionate Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a liqu ...

(instead of acetate) to the growing compound during biosynthesis. The following internal

cyclization A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where ...

proceeds through a Diels–Alder reaction catalyzed by an unknown

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. A ...

. The origin of the subsequent oxidations at positions 1, 2 and 8 have yet to be characterized, but they have been shown not to originate from acetate. It has been theorized that

cytochrome P-450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

is responsible for the oxidation at these three positions since its inhibition produces probetaenone 1, the non-oxidized form of betaenone B. Betaenone B synthesis

References

{{reflist Decalins Cyclic ketones Tertiary alcohols Primary alcohols Polyketides