Partial Synthesis of Vitamin B12 Coenzyme and Analogues
Abstract
THE structure of the vitamin B12 coenzyme1 has been determined recently by X-ray crystallography2. It seemed possible (cf. ref. 3) that a synthesis of this compound, which contains a 5'-deoxyadenosyl group attached direct to the cobalt atom by a cobalt-carbon bond, could be achieved from reduced hydroxocobalamin and a suitably 5'-substituted adenosine derivative. 5'-Tosyladenosine is known4 to cyclize easily to the tosylate of cycloadenosine but the 5'-tosyl-2',3'-isopropylidene derivative of adenosine can be prepared without difficulty4. Hydroxocobalamin was reduced in aqueous or ethanolic solution with sodium borohydride and reacted with this adenosine derivative. A product which had the properties expected of an isopropylidene derivative of the coenzyme was isolated from the reaction mixture in poor to moderate yield. Following a suggestion from Dr. V. M. Clark, whom we thank for his interest, we then attempted to reduce the cobalamin not just to the brown vitamin B12r (ref. 5), believed to be a cobalt II derivative, but to the grey-green compound containing cobalt in a lower oxidation state6. This compound can be prepared under anaerobic conditions from hydroxocobalamin with sodium borohydride, chromous acetate in ethylenediamine tetra-acetic acid buffer at pH. 9.5, or with zinc dust and dilute acetic acid. Under acid or alkaline conditions it reacts rapidly with a range of alkylating agents to give good yields of coenzyme analogues. In contrast, vitamin B12r, the exclusive product obtained from hydroxocobalamin and chromous acetate at pH 5, is quite unreactive.
- Publication:
-
Nature
- Pub Date:
- June 1962
- DOI:
- 10.1038/1941175a0
- Bibcode:
- 1962Natur.194.1175S