Synthesis and properties of formylcobalamin and propionylcobalamin, novel acylcobalamins.

Abstract

Formylcobalamin (formyl-Cbl), a C1-unit carrying corrinoid, and propionylcobalamin (propionyl-Cbl) were synthesized for the first time, and their properties were compared with those of acetylcobalamin (acetyl-Cbl). Formyl-Cbl, acetyl-Cbl, and propionyl-Cbl were decomposed by a NH2OH treatment, forming formo-, aceto-, and propionohydroxamic acids, respectively, which offers a proof for the presence of "activated" acyl groups and for their structures of Co-acyl-Cbls. These results, together with chromatographic, electrophoretic, and spectroscopic properties, indicate that the acyl-Cbls synthesized are actually formyl-Cbl, acetyl-Cbl, and propionyl-Cbl. Spectroscopic and electrophoretic properties were consistent with the σ-donor strength or trans-effect increasing in the order: formyl<acetyl<propionyl. All acyl-Cbls underwent the Co-C bond cleavage upon photo-irradiation with a tungsten light bulb as well as upon treatment with alkali, forming aquacobalamin (aqCbl) and hydroxocobalamin (OH-Cbl), respectively, under air. Formyl-Cbl was thermally unstable and decomposed to aqCbl, and the thermal stability in neutral solution was much lower than in diluted HCl. In contrast, acetyl-Cbl and propionyl-Cbl were heat-stable under these conditions. Formyl-Cbl was essentially unsusceptible to unbufferized KCN solution, although acetyl-Cbl and propionyl-Cbl were rapidly converted to dicyanocobalamin under the same conditions. Such abnormal behaviors of formyl-Cbl suggest that it mainly exists in a hydrated form as formaldehyde.