SYNTHESIS, CHARACTERIZATION, AND ACID-INDUCED DECOMPOSITION OF THE ALPHA-DIASTEREOMERS AND BETA-DIASTEREOMERS OF (2-HYDROXYETHYL)COBALAMINS AND (2-ALKOXYETHYL)COBALAMINS AND COBINAMIDES

A series of (alkoxyethyl)cobalt corrinoids (ROCH2CH2CoC, R = H, C6H5, (CH3)2CH, CH3, CH3CH2, CF3CH2) has been prepared including the alpha- and beta-diastereomers of the (alkoxyethyl)cobalamins (ROCH2CH2Cbl's) and the alpha- and beta-diastereomers of the (alkoxyethyl)cobinamides (ROCH2CH2Cbi's). In addition, the deuterated analogue of (beta-hydroxyethyl)cobalamin ([1,2-(H-4)-H-2]-beta-HOCH2CH2Cbl) and the C-13-enriched analogues of all four of the hydroxyethyl complexes (alpha- and beta-[1,2-(C-2)-C-13]-HOCH2CH2Cbl's and alpha- and beta-[1,2-(C-2)-C-13]-HOCH2CH2Cbi's) have been prepared. These compounds have been characterized by UV-visible spectroscopy, GC/MS identification of the organic products of their solid-state anaerobic pyrolysis, FAB MS, and H-1, H-2, C-13, F-19, and C-13-edited H-1 NMR spectroscopy. All of the compounds are acid labile, decomposing with strictly first-order kinetics (at a given pH) at pH's of 0-4.4 in aqueous media and in aqueous sulfuric acid. The products of this decomposition for the beta-ROCH2CH2Cbl's were determined to be aquocobalamin (by UV-visible spectroscopy and HPLC retention), ethylene, and the alcohol, ROH (by GC/MS). Second-order rate constants have been determined for the base-on and base-off species of the beta-ROCH2CH2Cbl's as well as for the alpha-ROCH2CH2Cbl's and the alpha- and beta-ROCH2CH2Cbi's. The reactivity is significantly dependent on the nature of R and varies by about 40-fold across each series of (alkoxyethyl)cobalt corrinoids. In addition, the base-on species of the beta-ROCH2CH2Cbl's are found to be 43- to almost 100-fold more reactive than the base-off species. Unlike the analogous cobaloximes in which the acid-induced decomposition is known to proceed via a sigma-bonded ethylcobaloxime carbonium ion intermediate, no evidence of any kind could be found for the presence of an intermediate in the acid-induced decomposition of the (alkoxyethyl)cobalt corrinoids. The simplest mechanism which accounts for the data is thus a concerted elimination of the alcohol and the dealkylated cobalt corrinoid from the beta-oxygen-protonated species, RO(H)CH2CH2CoC+.