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Electrochemical Synthesis and Structure Analysis of Neocoenzyme B 12 – An Epimer of Coenzyme B 12 with a Remarkably Flexible Organometallic Group
Author(s) -
Kontaxis Georg,
Riether Doris,
Hannak Renate,
Tollinger Martin,
Kräutler Bernhard
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990609)82:6<848::aid-hlca848>3.0.co;2-l
Subject(s) - chemistry , stereochemistry , mutase , conformational isomerism , heteronuclear molecule , crystallography , ligand (biochemistry) , cofactor , corrin , population , organometallic chemistry , crystal structure , nuclear magnetic resonance spectroscopy , molecule , organic chemistry , ring (chemistry) , enzyme , biochemistry , receptor , demography , sociology
In neocoenzyme B 12 (=(5′‐deoxy‐5′‐adenosyl)‐13‐epicob(III)alamin; 5 ), an epimer of coenzyme B 12 ( 1 ), the organometallic group and a propanamide side chain of the vitamin‐B 12 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 B 12 ( 5 ; 89% yield) and methyl‐13‐epicobalamin ( 6 ; 88% yield) were prepared from neovitamin B 12 ( 4 ) by electrochemical 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 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 B 12 ( 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‐B 12 ‐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 .