Total synthesis of natural (−)- and unnatural (+)-Melearoride A. Issue 10 (7th March 2019)

• Record Type: Journal Article
• Authors: Reed, Carson W.; Fulton, Mark G.; Nance, Kellie D.; Lindsley, Craig W.
• Is Part Of: Tetrahedron letters. Volume 60:Issue 10(2019)
• Page Start: 743
• Page End: 745
• Publication Date: 2019-03-07
• Subjects: Melearoride A -- Total synthesis -- Macrolides -- Asymmetric alkylation; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2019.02.006
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: First total synthesis of (−)-Melearoride A. Total synthesis of (+)-Melearoride A. A concise 13 step synthesis from chiral pool starting materials. High yielding RCM to close the 13-membered macrocycle. Abstract: This communication details the first total synthesis of the 13-membered macrolide, (−)-Melearoride A, as well as unnatural (+)-Melearoride A. The synthesis features a concise 13 step synthesis (11 steps longest linear sequence) that offers flexible stereo-control and multiple opportunities for unnatural analog synthesis to delve into antifungal SAR. The route features a cuprate addition, an Evans asymmetric alkylation, and a ring-closing metathesis (RCM) to close the 13-membered macrocyclic core.