The Asymmetric Synthesis of Tetrahydrolipstatin

Abstract

The 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'sl andmark synthetic effort there have been numeroust otal and formal syntheses of THL, which have involvedadiverse range of approaches. These various syntheses can be classified by the methodst hat were used to install the stereochemistry,f or instance, chiral auxiliary,a symmetrica ldol, asymmetric allylation/crotylation, asymmetricr eductions,a symmetricr esolutions, asymmetric oxidations, and chiron approach. These routes also feature the elegant use of ac hiral phosphate template, at andem [2+ +2]-Mukaiyama aldol-lactonization, an anti-aldol segment via an on-aldol route, aP rins cyclization,a nd an epoxide carbonylation.

Neurochemical Regulators of Food Behavior for Pharmacological Treatment of Obesity: Current Status and Future Prospects

“…It is the only agent approved in the European Union for weight loss. Numerous total syntheses of orlistat have been reported (Figure 6) [136][137][138][139][140].…”

Green pathway to the synthesis of some spirooxindole derivatives using NGO/PMA as a new and effective solid acid catalyst

“…Spirooxindole‐based products display a wide range of biological activities 31–35 such as anticancer, 36 contraceptive, 37 antimigraine, 38 antimycobacterial, 39 and antimicrobial 40 activity. Due to the special properties of these compounds, various methods were reported for their synthesis 41–50 .…”

Recent Advances in Green Synthesis of 3,3′‐Spirooxindoles via Isatin–based One–pot Multicomponent Cascade Reactions in Aqueous Medium

“…Other 3,3′‐spirooxindole compounds also display a variety of important biological activities, such as anti‐HIV, anti‐cancer, anti‐tuberculosis, anti‐oxidation, anti‐fungus, anti‐malarial and other pharmacological activities . The a ‐keto amide structure of isatins enables them to be excellent carbonyl electrophiles and allows a vast number of reactions initiated by nucleophilic attack on the C3 carbonyl group . Therefore, isatins are widely used as starting materials in synthesizing 3,3′‐spirooxindole derivatives.…”