Partial Synthesis of Coenzyme B 12 from Cobyric Acid

Here we report the direct chemical synthesis of coenzyme B 12 (AdoCbl) from Co β ‐5′‐deoxyadenosylcobyric acid (AdoCby) and the preparation of the latter from crystalline CN ,H 2 O‐cobyric acid ( CN ,H 2 OC by). AdoCby is a suggested common key intermediate in the biosynthesis of AdoCbl and of other cobamides in microorganisms. AdoCby was thoroughly characterized by spectroscopic means, including homo‐nuclear and hetero‐nuclear NMR , as such data are not available in published work. AdoCbl was prepared from AdoCby in one‐step in over 85% yield, by covalent attachment in aqueous solution of the integral B 12 ‐nucleotide moiety using 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide ( EDC · HC l) and N ‐hydroxybenzotriazole ( HOB t) as coupling reagents. By the same procedure crystalline vitamin B 12 ( CNC bl) was also prepared in 92% yield from CN ,H 2 OC by. Coordination of the B 12 ‐nucleotide base at the Co α ‐face of AdoCby or of CN ,H 2 OC by was indicated to assist in the efficient covalent coupling at the activated f ‐side chain function to furnish the complete corrinoids AdoCbl and CNC bl.