Homocoenzyme B 12 and Bishomocoenzyme B 12 : Covalent Structural Mimics for Homolyzed, Enzyme‐Bound Coenzyme B 12

Efficient electrochemical syntheses of “homocoenzyme B 12 ” ( 2 , Co β ‐(5′‐deoxy‐5′‐adenosyl‐methyl)‐cob( III )alamin) and “bishomocoenzyme B 12 ” ( 3 , Co β ‐[2‐(5′‐deoxy‐5′‐adenosyl)‐ethyl]‐cob( III )alamin) are reported here. These syntheses have provided crystalline samples of 2 and 3 in 94 and 77 % yield, respectively. In addition, in‐depth investigations of the structures of 2 and 3 in solution were carried out and a high‐resolution crystal structure of 2 was obtained. The two homologues of coenzyme B 12 ( 2 and 3 ) are suggested to function as covalent structural mimics of the hypothetical enzyme‐bound “activated” (that is, “stretched” or even homolytically cleaved) states of the B 12 cofactor. From crude molecular models, the crucial distances from the corrin‐bound cobalt center to the C5′ atom of the (homo)adenosine moieties in 2 and 3 were estimated to be about 3.0 and 4.4 Å, respectively. These values are roughly the same as those found in the two “activated” forms of coenzyme B 12 in the crystal structure of glutamate mutase. Indeed, in the crystal structure of 2 , the cobalt center was observed to be at a distance of 2.99 Å from the C5′ atom of the homoadenosine moiety and the latter was found to be present in the unusual syn conformation. In solution, the organometallic moieties of 2 and 3 were shown to be rather flexible and to be considerably more dynamic than the equivalent group in coenzyme B 12 . The homoadenosine moiety of 2 was indicated to occur in both the syn and the anti conformations.