The Asymmetric Synthesis of Tetrahydrolipstatin

Abstract

AbstractThe various syntheses of the over‐the‐counter anti‐obesity drug tetrahydrolipstatin (also known as Orlistat) are reviewed. The 31 various syntheses cover the development of enantioselective natural products synthesis since the first synthesis of tetrahydrolipstatin (THL) by Schneider in 1987. After Schneider's landmark synthetic effort there have been numerous total and formal syntheses of THL, which have involved a diverse range of approaches. These various syntheses can be classified by the methods that were used to install the stereochemistry, for instance, chiral auxiliary, asymmetric aldol, asymmetric allylation/crotylation, asymmetric reductions, asymmetric resolutions, asymmetric oxidations, and chiron approach. These routes also feature the elegant use of a chiral phosphate template, a tandem [2+2]‐Mukaiyama aldol‐lactonization, an anti‐aldol segment via a non‐aldol route, a Prins cyclization, and an epoxide carbonylation.