Polyketide acetogenin

Over the past quarter-century more than 10,000 compounds have been reported from marine-derived organisms. These compounds encompass a wide variety of chemical structures including acetogenins, polyketides, terpenes, alkaloids, peptides and many compounds of mixed biosynthesis. A number of excellent books and reviews document the diversity of both structures and bioactivities which have been observed for marine-derived compounds. ... 

Collie s hypothesis that aromatic compounds are made biologically from ethanoic acid was greatly expanded by A. J. Birch to include an extraordinary number of diverse compounds. The generic name acetogenin has been suggested as a convenient classification for ethanoate (acetate)-derived natural products, but the name polyketides also is used. Naturally occurring aromatic compounds and quinones are largely made in this way. An example is 2-hydroxy-6-methylbenzoic acid formed as a metabolite of the mold Penicillium urticae ... 

Metabolites of the phylum Porifera account for almost 50% of the natural products reported from marine invertebrates. Of the 2609 poriferan metabolites, 98% are derived from amino acid, acetogenin, or isoprenoid pathways. Isoprenoids account for 50% of all sponge metabolites, while amino acid and polyketide pathways account for 26% and 22%, respectively. A significant number of sponge metabolites appear to be derived from mixed biosynthetic pathways. Most structures reported containing carbohydrate moieties were glycosides. 

Tanaka has shown that in his synthesis of a variety of diastereomeric annonac-eous acetogenins (9, Scheme 3) the carbinol stereocenter can be generated with predictable selectivity by reagent control of either enantiomer of the chiral ligand [24], He applied this method in the total synthesis of murisolin (9, n= 1), a member of family of over 350 natural polyketides isolated from various annon-aceaes plants (Scheme 4). 

These are called acetogenins (or sometimes polyketides). Many of these compounds are aromatic, and their pathway of formation is the principal means of synthesis of the benzene ring in nature. Not all are lipids, because partial reduction often leaves oxygen-containing groups, which render the product soluble in water. 

Total Stereoselective Synthesis of Acetogenins of Annonaceae A New Class of Bioactive Polyketides... 

Because of the diversity of marine organisms and habitats, marine natural products encompass a wide variety of chemical classes, including terpenes, shikimates, polyketides, acetogenins, peptides, alkaloids of varying structures, and a multitude of compounds of mixed biosynthesis. In the past decade alone, the structures of over 5000 marine natural products have been published (3-10). 

Polyketides. Collective name for natural products produced biosynthetically by way of poly(/5-oxo-carboxylic acids). The name was derived in 1907 by Collie on the basis of the hypothesis that natural prt ucts may be formed by multiplication of ketene (HjCsC o) units. The P. chains are constructed on multienzyme complexes (polyketide synthases) from acetyl- and malonyl-CoA ( acetogenins) or also by use of propio-nyl- and/or butyryl-CoA. Depending on the number of building blocks the natural products ate classified as triketides (n=3), tetraketides (n=4), etc. 

The stem bark of Goniothalmus giganteus (Annonaceae) contains the related compounds, goniothalenone (altholac-tone) (1) and goniolhalamin (2), in addition to a series of acetogenins (Fig. 10.1) see Polyketides) (McLaughlin, 1991). 

Polyketides (acetogenins) show a regular pattern of oxygen-substituted and oxygen-free C-atoms at least in part of the molecule. Most are derivatives of (—CHg—CO—)n-polyketo acids. However, compounds are also formed from (—CHCHg—CO—)n-polyketo acids (D 4). With the exception of a few derivatives... 

Figure 4.1 The condensation offour acetic acid units to give an intermediate polyketide which by further reaction gives an acetogenin. The polyketide is a formal intermediate, not always having a real existence...

Given the structure of a substance we can usually work back to the polyketide from which it must be derived. When side chains occur in acetogenins, these are always derived from the tail of the polyketide, never the carboxylic acid head . The carbonyl oxygen nearest to the... 

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