Semisynthetic and biotransformation studies of (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol.

Tobacco-derived (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (2) were first shown to display potential antitumor-promoting activity in the mid-1980s. However, very little is currently understood regarding the structural activity relationships of tobacco cembranoids. The aim of this present study was to explore antiproliferative activity of various derivatives of (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) using semisynthetic and biotransformation approaches. Derivatives of 1 include esterified, oxidized, halogenated, and nitrogen- and sulfur-containing compounds (3–17). Biotransformation of 1 using Mucor ramannianus ATCC 9628 and Cunninghamella elegans ATCC 7929 afforded the known 10S,11S-epoxy analogue of 1 (4) as the main metabolite. Biotransformation of the 6-O-acetyl analogue (3) using the marine symbiotic Bacillus megaterium strain MO31 afforded (1S,2E,4S,6R,7E,11E,10R)-2,7,11-cembratriene-4,6,10-triol (18). (1S,2E,4S,6R,7E,11E,...