Highly Efficient, Convergent, and Enantioselective Synthesis of Phthioceranic Acid

Abstract

A new strategy for highly concise, convergent, and enantioselective access to polydeoxypropionates has been developed. ZACA-Pd-catalyzed vinylation was used to prepare smaller deoxypropionate fragments, and then two key sequential Cu-catalyzed stereocontrolled sp(3)-sp(3) cross-coupling reactions allowed convergent assembly of smaller building blocks to build-up long polydeoxypropionate chains with excellent stereoselectivity. We employed this strategy for the synthesis of phthioceranic acid, a key constituent of the cell-wall lipid of Mycobacterium tuberculosis, in just 8 longest linear steps with full stereocontrol.

Keywords: ZACA reaction; asymmetric synthesis; cross-coupling; natural product synthesis; polydeoxypropionates.