Synthetic and biosynthetic studies on the polyketide metabolites LL-D253a and averufin

In Chapter 1 a brief outline of the range of naturally-occurring oxygen heterocycles is presented. This is follow ed by a com prehensive review of non-flavanoid naturally-occurring chromanones, including reference to any im portant biosynthetic studies. This is follow ed by a review of the synthesis of such compounds, concentrating on more recent developmentsChapter 2 concerns the biosynthesis of the chrom anone LL-D253a, a metabolite of P. p ig m e ntivora . A review of previous studies is presented, followed by a brief account of the existence of the phenonium ion, though t to be an intermediate in the biosynthesis of LL-D253a. The incorporation of sodium [2 - 2H3,13C]-acetate, and of diethyl [ 2 - 13C]-malonate, into LL-D253a give an insight into the mechanism of its form ation. Chemical manipulation of deuterium labelled LL-D253a derivatives has supported the existence of a "phenonium'' intermediate. Chemical synthesis of some postulated prrecursors to Ll-D253a was undertaken.Chapter 3 concerns the biosynthesis of averufin, known to be a precursor to aflatoxin B-|. An overview of aflatoxin biosynthesis is presented, and includes a detailed review of relevant studies reported since 1980. The incorporation of [ 2 - 2H2]-hexanoic acid, and of diethyl [ 2 - 13C]-malonate, into averufin is reported. These results confirm that averufin is a decaketide, but during its biosynthesis it is able to exchange with endogenous hexanoate. Attem pted chemical manipulation of averufin, and incorporation of [7 - 2H2]-averufin into aflatoxin B-, is discussed