FACILE ALPHA-BETA DIASTEREOMERISM IN ORGANOCOBALT CORRINOIDS - SYNTHESIS, CHARACTERIZATION, AND COMPLETE H-1 AND C-13 NMR ASSIGNMENTS OF ALPHA-5'-DEOXYADENOSYLCOBINAMIDE AND ALPHA-5'-DEOXYADENOSYLCOBALAMIN

Reductive alkylation of cobinamide in zinc/acetic acid with ether 5'-deoxy-5'-iodoadenosine or 5'-bromo-5'-deoxyadenosine has been found to produce a pair of diastereomeric 5'-deoxyadenosylcobinamides in which the deoxyadenosyl ligand is in the ''upper'' (or beta) axial ligand position (beta-AdoCbi) or in the ''lower'' (or alpha) axial ligand position (alpha-AdoCbi). Unlike the case with other alkyl halides, the ratio of product diastereomers has been found to depend on time, the halide leaving group, and the concentration of the 5'-deoxy-5'-haloadenosine. Thus, reductive alkylation with 5'-chloro-5'-deoxyadenosine gave only beta-AdoCbi. While the diastereomers of AdoCbi proved to be equally labile toward reductive dealkylation by zinc/acetic acid (as is the case for other pairs of alpha- and beta-RCbi's), alpha-AdoCbi was dealkylated rapidly by borohydride while the beta diastereomer was stable. As a result, reductive adenosylation with borohydride as the reducing agent leads exclusively to beta-AdoCbi regardless of the alkylating agent. The alpha diastereomer of 5-deoxyadenosylcobalamin (alpha-AdoCbl) has also been synthesized in zinc/phosphoric acid media. The novel alpha diastereomers of the 5'-deoxyadenosylcobalt corrinoids have been characterized by UV-visible spectroscopy, HPLC, and FAB-MS. In addition, the H-1 and C-13 NMR spectra of both diastereomers have been completely assigned using a combination of homonuclear (COSY, ROESY, and HOHAHA) and inverse detected heteronuclear (HMQC and HMBC) 2-D NMR methodologies. These assignments permit the first comparison of the NMR spectra of pairs of diastereomeric alkylcobalt corrinoids as the H-1 and C-13 NMR spectra of beta-AdoCbi and base-off beta-AdoCbl have previously been assigned by others. Significant differences in chemical shift between the pairs of diastereomers at peripheral corrin substituents are most likely attributable to differences in the alpha- and beta-face environments in the absence or presence of a 5'-deoxyadenosyl moiety at that face. However, the largest chemical shift differences occur in the corrin ring and suggest that the diastereomeric 5'-deoxyadenosylcobalt corrinoids may have significantly different corrin ring conformations.