RARE ALPHA-ALKYL ISOMERS OF COBALAMINS - SYNTHESIS, CHARACTERIZATION, AND PROPERTIES OF 2 DIASTEREOMERS OF THE ALPHA-ALKYLCOBALAMIN, ALPHA-(2-OXO-1,3-DIOXOLAN-4-YL)COBALAMIN

The synthesis, characterization, 2-D NMR (HOHAHA, NOESY, HMQC, and HMBC spectroscopies), and reactivities of a new alpha-alkylcobalamin are described (an alpha-alkylcobalamin has the axial alkyl group attached to the cobalt from the ''bottom'' or alpha-face of the corrin ring). The alpha-alkylcobalamin, alpha-(2-oxo-1,3-dioxolan-4-yl)cobalamin (1), is the first example of an alpha-alkylcobalamin with a secondary alkyl group and the first case with a chiral alkyl group (i.e., where alpha-alkylcobalamin diastereomers are produced). It is also the first alpha-alkylcobalamin completely characterized (HPLC, UV-visible, IR, FAB-MS, and 1- and 2-D NMR methods). Anaerobic photolysis converts 1 to its beta-isomer, beta-(2-oxo-1,3-dioxolan-4-yl)cobalamin (2), where the alkyl group is now attached to the cobalt from the usual, beta or ''top'' side of the corrin. Physical properties previously unavailable for any alpha-alkylcobalamin were measured for 1, notably the beta-side axial base binding constants [for 1-methylimidazole, pyridine, (+/-)-histidine, and 1,5,6-trimethylbenzimidazole], and the thermal stability of the individual diastereomers of 1. Possible mechanisms for, and the factors controlling, the formation of alpha- and beta-alkylcobalamins are presented and discussed.