Microbial transformation of sesquiterpenes, (-)-ambrox® and (+)-sclareolide

The microbial transformation of (-)-Ambrox(R) (1), a perfumery sesquiterpene, by a number of fungi, by means of standard two-stage-fermentation technique, afforded ambrox-1alpha-ol (2), ambrox-1alpha,11alpha-diol (3), ambrox-1alpha,6alpha-diol (4), ambrox-1alpha,6alpha,11alpha-triol (5), ambrox-3-one (6), ambrox-3beta-ol (7), ambrox-3beta,6beta-diol (8), 13,14,15,16-tetranorlabdane-3,8,12-triol (9), and sclareolide (10) (Schemes 7 and 2). Further incubation of compound 10 with Cunninghamella elegans afforded 3-oxosclareolide (11), 3beta-hydroxysclareolide (12), 2alpha-hydroxysclareolide (13), 2alpha,3beta-dihydroxysclareolide (14), 1alpha,3beta-dihydroxysclareolide (15), and 3beta-hydroxy-8-episclareolide (16) (Scheme 3). Metabolites 2-5, 12, 13, and 16 were found to be new compounds. The major transformations include a reaction path involving hydroxylation, ether-bond cleavage and inversion of configuration. Metabolites 11-16 of sclareolide showed significant phytotoxicity (Table 1). The structures of the metabolites were characterized on the basis of spectroscopic techniques.