Tetrahydrolipstatin (THL) is an over-the-counter antiobesity drug, has anticancer activity, and might help against the gastrointestinal disease giardiasis.
Geoffrey W. Coates, Cornell University, Ithaca, NY, USA, George A. O’Doherty, Northeastern University, Boston, MA, USA, and colleagues have synthesized THL and seven stereoisomers in a concise enantioselective syntehsis. Their ten steps synthesis led to an overall yield of 31 % and started from an achiral ynone. A bimetallic [Lewis acid]+[Co(CO)4]− catalyst is used for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone.
According to the authors these findings prove the suitability of the bimetallic carbonylation catalyst for the synthesis of complex molecules which makes it attractive for the synthesis and medicinal chemistry studies of natural products.
- Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols,
Michael Mulzer, Brandon J. Tiegs, Yanping Wang, Geoffrey W. Coates, George A. O’Doherty,
J. Am. Chem. Soc. 2014.