Chemoenzymatic Generation of Thio-analogues of δ-Cadinene, δ-Cadinol, and a Thio-diquinane Using 8-Thio-farnesylpyrophosphate.

The synthesis of 8-thio-farnesylpyrophosphate is reported, which was subjected to biotransformations with different sesquiterpene synthases. The 9-thio-analogues of δ-cadinene and δ-cadinol were formed by the sesquiterpene synthases Cop4 and Omp7. In contrast, the fungal sesquiterpene synthase BcBOT2 yielded a diquinane terpenoid that contains a keto and thiol group. The formation of the two former "sulfo"-terpenoids can be rationalized by following the route proposed for δ-cadinene and δ-cadinol. The latter can be regarded by the result of a late-stage hydrolysis product during the analogous pathway to presilphiperfolan-8β-ol, the natural product of BcBOT2. The olfactoric analysis of the three "sulfo"-sesuiterpenoids revealed a stale odor for the cadinene derivatives, whereas the ketothiol diquinane exhibits a spicy aroma with a subtle chili note.