MECHANISM OF ACTION OF VITAMIN-B-12 - ULTRAFAST RADICAL CLOCKS PROVIDE NO EVIDENCE FOR RADICAL INTERMEDIATES IN CYCLOPROPANE MODELS FOR THEMETHYLMALONYL-COA TO SUCCINYL-COA CARBON SKELETON REARRANGEMENT

To probe for free radical intermediates in the model studies for the c oenzyme B-12-dependent, methylmalonyl-CoA to succinyl-CoA carbon-skele ton rearrangement, new models incorporating cyclopropane rings (unsubs tituted 23 and 2-phenyl-substituted 28) at the 2-position were develop ed. The reaction of 23 or 28 with vitamin B-12s gives only rearranged succinate 24 or 29, respectively, with the cyclopropyl group intact. W hen this reaction was carried out in EtOD/D2O, a monodeuterided produc t, 24-d(1) or 29-d(1), was obtained and the deuterium was incorporated at the 2-position. Control reactions of the 2-phenylselenylsuccinate with tri-n-butyltin hydride yielded the ring-opened 2-propanylidenesuc cinate via a free radical pathway. The results suggest that the skelet al rearrangement step in the B-12-catalyzed isomerization of methylmal onyl-CoA to succinyl-CoA occurs not by a radical pathway but by an ani onic or organocobalt pathway.