Total Synthesis of (−)-Lasonolide A

• DOI: 10.1021/jacs.6b05127
• Publication Date: 2016-08-22T16:30:44Z
• Authors: Barry M. Trost; Craig E. Stivala; Daniel R. Fandrick; Kami L. Hull; Audris Huang; Caroline Poock; Rainer Kalkofen
• Keywords: Tetrahydropyran; Alkene; Alkyne; Kinetic resolution

The lasonolides are novel polyketides that have displayed remarkable biological activity in vitro against a variety of cancer cell lines. Herein we describe our first-generation approach to the formal synthesis lasonolide A. key findings from these studies ultimately allowed us go on and complete total convergent unites two highly complex fragments utilizing Ru-catalyzed alkene-alkyne coupling. This type coupling typically generates branched products; however, through detailed investigation, now able demonstrate subtle structural changes substrates can alter selectivity favor formation linear product. features number atom-economical transformations which highlighted by discovery an engineered enzyme perform dynamic kinetic reduction β-ketoester establish absolute stereochemistry southern tetrahydropyran ring with high levels enantioselectivity.