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

  • J Nat Prod. 2025 Jul 25;88(7):1653-1662. doi: 10.1021/acs.jnatprod.5c00409.
Birk Jäger  1 ,  Jan Luca Budde  1 ,  Norman Birke  1 ,  Maximilian Hauke  1 ,  Andreas Kirschning  1  2
Affiliations
  • 1. Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
  • 2. Uppsala Biomedical Center (BMC), Uppsala University, Husargatan 3, 752 37 Uppsala, Sweden.
PMID: 40673503 DOI: 10.1021/acs.jnatprod.5c00409
Abstract

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.

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