Stereoselectivity during fungal sulphoxidations of 1,3-dithiolanes

Abstract

Mono- and di-sulphoxide products were obtained after addition of 1,3-dithiolane (1), 2-methyl-1,3-dithiolane (4), and 2-t-butyl-1,3-dithiolane (7) as substrates to growing cultures of Aspergillus foetidus, Mortierella isabellina, and a Helminthosporium species. Enzyme-catalysed stereo differentiation between prochiral lone pairs on a sulphur atom gave optically active 1,3-dithiolane 1-oxide (2)(10–65% e.e.). The derived optically pure trans-1,3-dithiolane-1,3-dioxide (3) was obtained by fractional recrystallization. A stereopreference for the pro-R sulphur atom (61 and 66%) was observed during microbial oxidation of 2-methyl-1,3-dithiolane (4) and 2-t-butyl-1,3-dithiolane (7) respectively. The absolute stereochemistry of the dextrorotatory sulphoxide metabolites (2), t-(5), t-(8), and (3) was assigned the R configuration at the chiral sulphur atoms from c.d. spectroscopy.