EFFICIENT SYNTHESIS OF RADIOLABELED PROPIONYL-COENZYME-A AND ACETYL-COENZYME-A

The efficient microscale synthesis of [1-C-14]propio-nyl-CoA from comm ercially available sodium [1-C-14]-propionate using 1,1'-carbonyldiimi dazole in yields of nearly 70% is reported for the first time. A subst antial improvement in the process for making [1-C-14]acetyl-CoA from s odium [1-C-14]acetate was also achieved. Yields of greater than 90% we re consistently obtained for the latter synthesis. The salt-free CoA-t hioesters were obtained in homogenous form by reverse-phase HPLC. The products were judged to be pure by H-1 NMR analysis: neither iso-CoA a nalogs nor contaminants frequently found in commercial samples could b e detected. The samples of acetyl- and propionyl-CoA were shown to be radiochemically pure by HPLC and by analysis of the products of incuba tions with acetyl- and propionyl-CoA carboxylase. This highly efficien t synthesis is a cost-effective method for the preparation of radiolab eled CoA thioesters and can easily be adapted to the production of oth er acyl-CoA analogs. (C) 1995 Academic Press, Inc.