Electrochemical synthesis and structure analysis of neocoenzyme B-12 - An epimer of coenzyme B-12 with a remarkably flexible organometallic group

In neocoenzyne B-12 (= (5'-deoxy-5'-adenosyl)-13-epicob(III)alamin: 5). an epimer of coenzyme B-12 (1). the organometallic group and a propanamide sid e chain of the vitamin-B-12 ligand compete for the same region in space. In teresting consequences for structure and organometallic reactivity of this isomer of 1 are to he expected. Neocoenzyme B-12 (5; 89% yield) and methyl- 13-epicobalamin (6. 88% yield) were prepared from neovitamin B-12 (4) by el ectrochemical means (Fig. 3). The solution structure of the organometallic neovitamin-B-12 derivative 5 was analyzed by homonuclear and heteronuclear NMR spectroscopy. Comparison of the structures of 1 and 5 informed on the s tructural consequences of the epimerization at C(13) and revealed a remarka ble flexibility of the organometallic group in 5. In 5, both sterically int eracting functionalities (organometallic group and propanamide side chain a t C(13)) adapt their conformations dynamically to avoid significant mutual clashes As one consequence of this structural adaptation, the major conform ations of 5 feature counterclockwise and clockwise reorientations of the or ganometallic ligand with respect to its crystallographically determined pos ition in coenzyme B-12 (1). One of the dominant conformers of 5 exhibits an orientation of the organometallic functionality similar to that found in t he crystal structure of the coenzyme-B-12- dependent methylmalonyl CoA muta se. The present NMR study also revealed the significant population of syn-c onformers of the organometallic adenosine group, another remarkable feature of the solution structure of 5.