Rapid and scalable synthesis of chiral bromolactones as precursors to α-exo-methylene-γ-butyrolactone-containing sesquiterpene lactones. Issue 41 (11th October 2018)

• Record Type: Journal Article
• Authors: Lagoutte, Roman; Pastor, Miryam; Berthet, Mathéo; Winssinger, Nicolas
• Is Part Of: Tetrahedron. Volume 74:Issue 41(2018)
• Page Start: 6012
• Page End: 6021
• Publication Date: 2018-10-11
• Subjects: Sesquiterpene lactones -- Covalent inhibitors -- α-exo-methylene-γ-butyrolactones -- Bromolactones -- Enantioselective synthesis -- Barbier coupling; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.08.045
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The sesquiterpene lactones cover a diverse and pharmacologically important diversity space. In particular, the electrophilic α- exo -methylene-γ-butyrolactone moiety that is preponderant in this natural product family has been shown to readily engage in covalent inhibition via conjugate addition of cysteine residues in target proteins. However, the synthetic accessibility of sesquiterpenes or related probes to investigate their mode of action remains laborious. Herein, we present a rapid and scalable route to chiral bromolactones as enabling precursors in the synthesis of sesquiterpene lactones. Graphical abstract: