A Synthesis of Exiguaquinol Dessulfate. Issue 50 (26th October 2016)

• Record Type: Journal Article
• Authors: Schwarzwalder, Gregg M.; Scott, David R.; Vanderwal, Christopher D.
• Is Part Of: Chemistry. Volume 22:Issue 50(2016)
• Page Start: 17953
• Page End: 17957
• Publication Date: 2016-10-26
• Subjects: antibiotics -- epimers -- Heck cyclization -- natural product synthesis -- sulfation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201604506
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels–Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N ‐acyl hemiaminal, which was based upon an analysis of internal hydrogen‐bonding interactions with polar functional groups, was proven correct. A late‐stage intermediate did not demonstrate bactericidal activity against H. pylori cultures. Abstract : A desymmetrization strategy led to the synthesis of a congener of exiguaquinol, an inhibitor of the H. pylori MurI enzyme and a potential antibiotic. The pentacyclic architecture was accessed through convergent Diels–Alder and aldol additions, followed by a reductive Heck cyclization to forge the vicinal quaternary stereogenic centers.