title: Cobinamides as structural probes in B12-biosynthesis: synthesis and spectroscopic analysis of isomers of Co alpha,Co beta-dicyanocobinamide.
abstract: Vitamin B(12) and its coenzyme forms are cobalamins (i.e., cobamides, 'complete' with a 5,6-dimethylbenzimidazole nucleotide base), in which the particular corrinoid moiety of the cobinamides is conjugated to alpha-ribazole-3'-phosphate via a phosphate-diester group. Aside of being provided with their particular reactivity, required for their functions as organometallic cofactors in B(12)-dependent enzymes, the cobalamins also depend upon their specific three-dimensional buildup, to be able to adapt the unique constitution of 'base-on' corrinoids by intramolecular Co-coordination of the nucleotide base. We report rational partial syntheses and detailed spectral analyses of three close cobinamide isomers in their Co(alpha),Co(beta)-dicyano forms: of 13-epicobinamide (also called neocobinamide), of 176(S)-epicobinamide, and of 176-isocobinamide. Neocobinamide was obtained under acidic conditions as a degradation product of vitamin B(12). 176(S)-Epicobinamide and 176-isocobinamide were prepared by condensation of cobyric acid with (2S)-1-aminopropan-2-ol and with 3-aminopropan-1-ol, respectively. Natural cobinamide represents the corrinoid nucleus produced by proper microbial biosynthesis (as intermediate for the further assembly of the 'complete' corrinoid cofactors) or is required in some microorganisms, such as Escherichia coli, as an exogenously supplied unit for further biosynthetic buildup. The three compounds may thus be of use as structural probes for the biosynthetic capacity and tolerance in microorganisms, and (some of them) may serve as substrates as well, for further biosynthetic 'completion' of corrinoid cofactors or their analogues.
authors.affiliation: Institute of Organic Chemistry & Centre of Molecular Biosciences, Leopold-Franzens-Universität Innsbruck, Innrain 52a, A-6020 Innsbruck.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Murtaza
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kräutler
mesh_terms: D002942:Circular Dichroism; D003038:Cobamides / Q000138:chemical synthesis* / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D014805:Vitamin B 12 / Q000096:biosynthesis*
chemical_list: D003038:Cobamides; C017142:cobinamide; D014805:Vitamin B 12