A rapid method for the synthesis of methylmalonyl-coenzyme A and other CoA-esters

A rapid and high-yield synthesis of methylmalonyl coenzyme A is reported. The two-step procedure involves preparation of the thiophenyl ester of methylmalonic acid using dicyclohexylcarbodiimide as a condensing agent, followed by transesterification with coenzyme A, to yield methylmalonyl coenzyme A in 80% overall yield. Inclusion of an additional step, methylation of malonic acid with iodomethane, affords the opportunity for introducing a stable or radioactive isotope into the product. This method should be applicable for the syntheses of other coenzyme A esters that are of biochemical interest such as succinyl coenzyme A.