A Protecting-Group-Free Synthesis of (−)-Salvinorin A

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Contributors

Abstract

A concise enantioselective total synthesis of the neoclerodane diterpene (−)-salvinorin A is reported. The stereogenic center at C-12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two intramolecular Diels-Alder reactions were applied to generate the tricyclic core. A chemoselective Mitsunobu inversion of a syn 1,2-diol allowed for further streamlining of the original reaction sequence by two steps. Overall, (−)-salvinorin A was synthesized in only 16 steps starting from 3-furaldehyde with 1.4 % total yield. Furthermore, an alternative intramolecular Diels-Alder strategy employing a 2-bromo-1,3-diene moiety was investigated.

Details

Original languageEnglish
Pages (from-to)7968-7973
Number of pages6
JournalChemistry - A European Journal
Volume27
Issue number29
Publication statusPublished - 20 May 2021
Peer-reviewedYes

External IDs

PubMed 33784436

Keywords

ASJC Scopus subject areas

Keywords

  • Asymmetric catalysis, Cycloaddition, Mitsunobu reaction, Terpenoids, Total synthesis