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Synthesis 2014; 46(22): 3047-3058
DOI: 10.1055/s-0034-1378653
DOI: 10.1055/s-0034-1378653
paper
A Practical Synthesis of a Potent and Selective Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor
Further Information
Publication History
Received: 12 June 2014
Accepted: 21 July 2014
Publication Date:
25 August 2014 (online)
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Abstract
A practical synthesis of a potent, selective, and orally efficacious diacylglycerol acyltransferase-1 (DGAT-1) inhibitor, is described. This synthesis is suitable for multi-kilogram scale with high regioselectivity and stereoselectivity. The synthesis involves a Knoevenagel condensation with Meldrum’s acid followed by the stereoselective addition of phenyl cuprate, regioselective Friedel–Crafts acylation, cyclization, and a regioselective reduction through an enol triflate with catalytic platinum oxide to provide the desired compound in 5.2% yield over 12 steps.
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