Concise synthesis of thapsigargin from nortrilobolide. Issue 43 (21st October 2015)

• Record Type: Journal Article
• Authors: Crestey, François; Toma, Maddalena; Christensen, Søren Brøgger
• Is Part Of: Tetrahedron letters. Volume 56:Issue 43(2015)
• Page Start: 5896
• Page End: 5898
• Publication Date: 2015-10-21
• Subjects: Thapsigargin -- Nortrilobolide -- Semisynthesis -- Mn(OAc)3 -- α′-Acyloxylation; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2015.09.024
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: Herein, we describe an expedient synthesis of the hexaoxygenated guaianolide thapsigargin (1 ), a potent inhibitor of the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA), from the natural product nortrilobolide (2 ). This protocol involves three key steps: the one-pot substitution-oxidation reaction of an allylic ester into its corresponding α, β-unsaturated ketone, subsequent stereoselective α′-acyloxylation in the presence of Mn(OAc)3, and a highly stereoselective ketone reduction.