Synthesis of a Carba‐analog of S‐Acetyl CoA,Acetonyldethio CoA.Synthesis of a Carba‐analog of S ‐Acetyl Coenzyme A,Acetonyl‐dethio Coenzyme A; an Effective Inhibitor of Citrate Synthase

Acetonyldethio coenzyme A ( 1 ) together with its 2′‐phospho isomer 10 was obtained by the following reaction sequence: coupling of the glycol ketal 4 of 5‐amino‐2‐pentanone with N ‐benzyloxycarbonyl‐β‐alanine, fusion of the deblocked aletheine analog 5 with the lactone of D‐2,4‐dihydroxy‐3,3‐dimethylbutyric acid to yield the pantetheine analog 6 , which was phosphorylated at the 4′‐hydroxy group to form 7 , and then condensation with adenosine 2′,3′‐cyclic phosphate 5′‐phosphoric morpholide. The isomeric mixture exhibited strong competitive inhibition of citrate synthase ( S ‐acetyl CoA + oxaloacetate), K i being 13.2 μmol/l.