Reduction‐Labile Organo‐cob(III)alamins via Cob(II)alamin: Efficient Synthesis and Solution and Crystal Structures of [(Methoxycarbonyl)methyl]cob(III)alamin

Abstract

Dedicated to Professor Jack D. Dunitz on the occasion of his 80th birthday An efficient synthesis of Cob-[(methoxycarbonyl)methyl]cob(III)alamin (6) is reported as an example of a new method for the preparation of some easily reducible organo-cob(III)alamins via the alkylation of cob(II)alamin. The procedure represents a considerable improvement compared to earlier methods that were based on an alkylation of cob(I)alamin. Thus, aquacob(III)alamin chloride (5 ¥ Cl) was reduced to cob(II)alamin (4), either by controlled potential electrolytic reduction or with an excess of sodium formate as reducing agent. The solution of 4 was then treated with an excess of methyl bromoacetate while being reductively poised potentiostatically or kept reduced by the formate, to give crystalline 6 in a yield of up to 91%. The structure of 6 in aqueous solution was mainly established by the completely assigned 1 H-and 13 C-NMR spectra ( Table 1). The NOE data ( Table 2) were best rationalized by the presence of a single main conformation of the (methoxycarbonyl)methyl ligand. Single crystals of 6 were obtained by crystallization from an aqueous solution, and the crystal structure was determined by X-ray analysis at cryotemperatures. The NMR and crystallographic data of 6 indicated similar structures in aqueous solution and in the crystal with the (methoxycarbonyl)methyl ligand preferring a −southern× orientation in each case.Introduction. ± The standard method for the preparation of biologically important organo-cob(III)alamins, such as the adenosylcobamide coenzyme B 12 (1, 5'-deoxy-5'-adenosylcob(III)alamin) and methylcob(III)alamin (2), is based on the rapid reaction of the highly nucleophilic cob(I)alamin (3 À ; vitamin B 12s ) with alkylation reagents, such as alkyl halides or alkyl tosylates [1 ± 5]. The formation of 3 À requires strongly reducing conditions, with a rather negative half-wave potential of the critical redox couple cob(II)alamin (4; vitamin B 12r )/cob(I)alamin (3 À ) (E 1/2 (4/3 À ) À 0.85 V vs. SCE (H 2 O, pH 7) [6 ± 8]. Indeed, the route via cob(I)alamin (3 À ) in general provides a convenient way for the preparation of alkyl cob(III)alamins, as most Cob-organocob(III)alamins are only reductively cleaved at potentials considerably more-negative than À 0.85 V vs. SCE 3 )

Theoretical Investigations into the Intermediacy of Chlorinated Vinylcobalamins in the Reductive Dehalogenation of Chlorinated Ethylenes

“…On the other hand, reduction of its base-off form should be very facile and may account for consumption of 1 once it is formed. Preparation of authentic 1 under nonreducing conditions will be required to verify this pathway.…”

Homocoenzyme B12 and Bishomocoenzyme B12: Covalent Structural Mimics for Homolyzed, Enzyme‐Bound Coenzyme B12

“…28, 61, 62 Most of the standard procedures developed were based on the cobalt alkylation of the highly nucleophilic Co I corrins with organic alkylating agents63 and rely, therefore, both on methods for the efficient reduction of Co III corrins to cob( I )alamin and similar Co I corrins (and their in situ alkylation) and on the low tendency of alkyl Co III corrins to be reduced themselves under these conditions 28. 64 In cases where alkyl Co III corrins are themselves susceptible to reduction, sufficiently reactive alkylating agents can alternatively be used to alkylate Co II corrins 65. In the present work, homocoenzyme B 12 ( 2 ) and bishomocoenzyme B 12 ( 3 ) were prepared in pure crystalline form, free of coenzyme B 12 ( 1 ).…”

The Open‐Chain Trioxide CF3OC(O)OOOC(O)OCF3

“…The orientation of B12 relative to the bidentate ligand was investigated by ROESY experiments, as recently performed for a (methoxycarbonyl)methyl derivative 25. The spectra did not show cross peaks even at low‐temperature, thus indicating fast rotation of the complex.…”