Structure and absolute stereochemistry of thioacetal sulphoxides obtained by fungal metabolism of 2-alkyl-1,3-dithianes

Abstract

Monosulphoxide metabolites of 2-methyl-, 2-t-butyl-, 2,2-dimethyl-, and 2-methyl-2-t-butyl-1,3-dithiane have been isolated after addition of the thioacetals to growing cultures of the fungi Aspergillus foetidus, Mortierella isabellina and a Helminthosporium species. The optical yields of the chiral monosulphoxide metabolites (0–72%) were determined by n.m.r. analysis in (–)-phenyl- or 1-(+)-9-anthryl-2,2,2-trifluoroethanol–CDCl₃, solvent mixtures. The signs of Cotton effects obtained from c.d. spectra have been used to assign the absolute stereochemistry of the chiral thioacetal sulphoxides. Optically pure samples of 2,2-dimethyl-1,3-dithiane 1-oxide, cis-2-methyl-1,3-dithiane 1-oxide, and trans-2-methyl-1,3-dithiane 1-oxide, have been obtained by a chemical resolution method which provides confirmation of optical yields and absolute stereochemistry.

The fungal metabolism results indicate that the mono-oxygenase enzymes can stereo-differentiate between prochiral (diastereotopic) lone pairs on a sulphur atom and also between prochiral (enantiotopic) thioalkyl substituents on a carbon atom during the formation of monosulphoxides.