Total synthesis of pulvinones, 4-benzylidene-2-phenyltetronic acid pigments of fungi

Abstract

The application of 2-aryl O-methyltetronic acids (9) and (31) in the total synthesis of pulvinone pigments found in Aspergillus terreus and Suillus grevillei is described. Regioselective reductions of the corresponding maleic anhydride derivatives (8) and (30) with lithium aluminium hydride provide (9) and (31) respectively. Metallation of the tetronic acid (9) using lithium N-cyclohexyl-N-isopropylamide, followed by treatment with p-anisaldehyde and dehydration of the intermediate carbinol led to pulvinone (14). In a similar manner, condensations between (9), and 3,4- and 2,4-dimethoxybenzaldehydes produced pulvinones (17) and (18) respectively. The pulvinone (17) was identical with that obtained from the larch mushroom S. grevillei, but the isomeric pulvinone (18) was not identical with that purported to have this constitution and isolated from A. terreus.

Unambiguous syntheses of the prenylated pulvinones (23) and (24) from O-methyltetronic acids (9) and (31) respectively, and the appropriate aryl aldehydes, suggest that the biosynthesis of the bis-chromanated metabolite (22), from (1a)via(20) in A. terreus, proceeds by selective monoprenylation of (1a) leading to intermediate (4a), and by selective chromanation of (20) leading to intermediate (21).