Lactone ring polyketide-derived

Chemical study of a marine-derived Penicillium brocae, obtained from a tissue sample of a Fijian Zyzzya sp. sponge, resulted in the isolation and characterization of three novel cytotoxic polyketides, brocaenols A-C 136, 137a, and 137b, possessing an unusual enolized oxepine lactone ring system <2003JOC2014>. 

After synthesis of the lactone ring by polyketide synthases, some biosynthetic steps are involved in the modification of the lactone. In several macrolide biosyntheses, modifying by means of hydroxylation occurs more frequently. The enzyme involving hydroxylation of the polyketide-derived lactone ring is mainly cytochrome / -450 hydroxylase. The other modification is 0-methylation or reduction of the lactone ring. 

The mechanism for addition of two carbon units is like that of polyketide synthesis (Birch and Donovan, 1953). The starter unit is first converted to the CoA ester and C2 units added from malonyl-CoA (Fig. 10.2). The chain then cy-clizes in several ways which may be determined by the number of units added, the enzyme systems present, and other factors. Thus, one portion of the molecule is derived from shikimic acid and the other from acetate. In some cases, it is not possible to tell if a C -Cs precursor is extended by two acetate units or if a Cs-Ci precursor is extended by three units (Fig. 10.2). For example, paracotoin (3) [found in paracoto bark from Aniba pseudocoto (Lauraceae)] can be derived by either pathway (Fig. 10.3) (Manitto, 1981). After the chain is extended to six carbon atoms, cyclization occurs to produce a 6-membered lactone ring. 

Polyene macrolides are synthesited (as are other, better known nonpolyene macrolides) from two- and three-carbon units activated as malcmyl-CoA and methylmakxiyl-CoA. A few polyene macrolides contain an aromatic moiety that derives from p-aminobenzoyl-CbA and is used as starter unit. The different precursor units are condensed by polyketide synthases. Aminosugars, for example, mycosamine or pero mine, are attached glycosidi-cally to the lactone ring. 

The most important representatives of this group of polyketides are the afla-toxins synthesized by Aspergillus flavus. Aflatoxins are coumarin derivatives. The coumarin ring is fused with a bisdihydrofurano moiety plus either a cyclo-pentenone ring (B series) or a six-membered lactone (G series) (Fig. 80). 

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