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Synfacts 2014; 10(10): 1003
DOI: 10.1055/s-0034-1379036
DOI: 10.1055/s-0034-1379036
Synthesis of Natural Products and Potential Drugs
Synthesis of Tetrahydrolipstatin
Mulzer M, Tiegs BJ, Wang Y, Coates GW, * O'Doherty GA. * Northeastern University, Boston and Cornell University, Ithaca, USA
Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols.
J. Am. Chem. Soc. 2014;
136: 10814-10820
Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols.
J. Am. Chem. Soc. 2014;
136: 10814-10820
Further Information
Publication History
Publication Date:
17 September 2014 (online)
Key words
tetrahydrolipstatin - pancreatic lipase inhibitors - epoxide carbonylation - epoxyhomoallylic alcohols
Significance
Tetrahydrolipstatin (Xenical®) is a pancreatic lipase inhibitor that is marketed as a treatment for obesity. The eleven-step small-scale synthesis depicted (31% overall yield) features the regioselective carbonylation of the cis-epoxide I using the bimetallic [Lewis acid]+[Co(CO)4]– catalyst J to give the trans-β-lactone.
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Comment
Seven diastereoisomers of tetrahydrolipstatin were also prepared by this epoxide carbonylation route. Attempts to synthesize epoxide I via the direct DCC coupling of N-formyl-l-leucine with G occurred with appreciable amounts of epimerization.
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