Electrochemical Synthesis and Structure Analysis of Neocoenzyme B12 - An Epimer of Coenzyme B12 with a Remarkably Flexible Organometallic Group

Abstract

In neocoenzyme B12 (=(5′-deoxy-5′-adenosyl)-13-epicob(III)alamin; 5), an epimer of coenzyme B12 (1), the organometallic group and a propanamide side chain of the vitamin-B12 ligand compete for the same region in space. Interesting consequences for structure and organometallic reactivity of this isomer of 1 are to be expected. Neocoenzyme B12 (5; 89% yield) and methyl-13-epicobalamin (6; 88% yield) were prepared from neovitamin B12 (4) by electrochemical means (Fig. 3). The solution structure of the organometallic neovitamin-B12 derivative 5 was analyzed by homonuclear and heteronuclear NMR spectroscopy. Comparison of the structures of 1 and 5 informed on the structural consequences of the epimerization at C(13) and revealed a remarkable flexibility of the organometallic group in 5. In 5, both sterically interacting functionalities (organometallic group and propanamide side chain at C(13)) adapt their conformations dynamically to avoid significant mutual clashes. As one consequence of this structural adaptation, the major conformations of 5 feature counterclockwise and clockwise reorientations of the organometallic ligand with respect to its crystallographically determined position in coenzyme B12 (1). One of the dominant conformers of 5 exhibits an orientation of the organometallic functionality similar to that found in the crystal structure of the coenzyme-B12-dependent methylmalonyl CoA mutase. The present NMR study also revealed the significant population of syn-conformers of the organometallic adenosine group, another remarkable feature of the solution structure of 5.