Catalytic Activity of Novel Vitamin B12 Derivatives

Monday, 25 May 2015: 14:40
Lake Erie (Hilton Chicago)
D. Gryko (Institute of Organic Chemistry PAS,)
Among many biologically important metals, Co, in the form of vitamin B12 (cyano-cobalamin), plays a unique role. B12 coenzymes are indispensable for catalyzing enzymatic rearrangements (coenzyme B12, adenosylcobalamin) and methylation reactions (methylcobalamin).1 The special ability of vitamin B12 and other corrinoids to form a Co-C bond, combined with its facility in furnishing alkyl radicals via homolysis, has attracted the interest of many researchers, because corrinoids can be used as catalysts for C-C-bond forming reactions, which belong to the most challenging processes in organic synthesis. These catalytic reactions typically involve alkyl-cobalt complexes, which are formed in reactions of Co(I) species and an electrophile or a Co(II) and a radical. The most common chemical procedure utilizes the ‘supernucleophilicity’ of the Co(I) species (B12s) toward alkylating agents, such as alkyl halides. Homolysis of the Co-C bond generates a carbon-centered radical, which can, in situ, disproportionate, abstract H˙, or self-couple. In these reactions, B12 alkyl derivatives can be considered ‘reversible carriers’ of an alkyl radical.4

We have developed the synthesis of novel cobalamin derivatives possessing modified substituents at the periphery of the molecule. Our methodology presents a unique situation in which the six peripheral amide groups are transformed while leaving the bottom “f-loop” intact.2 These derivatives displayed UV-Vis spectra and oxidation-reduction characteristics similar to those of vitamin B12 but they differed significantly from the”incomplete” corrinoid heptamethyl cobyrinate, where the nucleotide moiety is absent, and instead, the second cyanide is coordinated. We confirmed that the intramolecular coordinating ligand plays a role in the radical reactions catalyzed by vitamin B12 derivatives. For example, the microwave-assisted homocoupling of benzylbromide3 catalyzed by cobalester produced a higher yield when compared to reactions catalyzed by reduced (CN)2Cob(OMe)7.Furthermore, the amphiphilic character of these newly synthesized derivatives facilitates carbon insertion into the vinyl C-H bond of olefins with alkyl diazoacetates in the presence of light.

1.   Banerjee, R. Chemistry and Biochemistry of B12, John Wiley & Sons, Inc, 1999

2.   Proinsias ó, K.; Giedyk, M.; Sharina, I.G.; Martin, E. and Gryko, D. ACS Med. Chem. Lett. 2012, 3, 476.

3.  Giedyk, M.; Fedosov, S.; Gryko, D. Chem. Commun. 2014, 50, 4674-4676.

4.   Shey, J.; McGinley, Ch.M.; McCauley, K.M.; Dearth, A.S.; Young, B.T. and van der Donk, W.A. J. Org. Chem. 2002, 67, 837.