A Practical Synthesis of a Potent and Selective Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor

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.

Key words

diacylglycerol acyltransferase-1 - hydrogenation - Knoevenagel­ condensation - Friedel–Crafts acylation - Friedel–Crafts alkylation - stereoselectivity - regioselectivitiy

• References

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