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Scalable Synthesis of (-)-Thapsigargin.

ABSTRACT: Total syntheses of the complex, highly oxygenated sesquiterpenes thapsigargin (1) and nortrilobolide (2) are presented. Access to analogues of these promising bioactive natural products has been limited to tedious isolation and semisynthetic efforts. Elegant prior total syntheses demonstrated the feasibility of creating these entitites in 36-42 step processes. The currently reported route proceeds in a scalable and more concise fashion by utilizing two-phase terpene synthesis logic. Salient features of the work include application of the classic photosantonin rearrangement and precisely choreographed installation of the multiple oxygenations present on the guaianolide skeleton.

SUBMITTER: Chu H

PROVIDER: S-EPMC5269647 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Scalable Synthesis of (-)-Thapsigargin.

Chu Hang H Smith Joel M JM Felding Jakob J Baran Phil S PS

ACS central science 20161219 1

Total syntheses of the complex, highly oxygenated sesquiterpenes thapsigargin (<b>1</b>) and nortrilobolide (<b>2</b>) are presented. Access to analogues of these promising bioactive natural products has been limited to tedious isolation and semisynthetic efforts. Elegant prior total syntheses demonstrated the feasibility of creating these entitites in 36-42 step processes. The currently reported route proceeds in a scalable and more concise fashion by utilizing two-phase terpene synthesis logic ...[more]

PMID: 28149952

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