Hydrophobic vitamin B12. Part 12. Preparation, characterization and enantioselective alkylation of strapped hydrophobic-vitamin B12

Abstract

Cyanocobalamin has been modified to afford a strapped hydrophobic vitamin B₁₂ by introducing a 1,3-phenylenediacetyl moiety into the peripheral site of the corrin's B ring. The modified complex was characterized by various spectroscopic methods and cyclic voltammetry in comparison with the corresponding data for a simple hydrophobic vitamin B₁₂ without a strapping moiety. The alkylation of hydrophobic vitamin B₁₂ derivatives with racemic 3-bromo-2-methylpropionic esters at the β-axial site was carried out in methanol, and extents of the enantioselectivity were examined by ¹H NMR spectroscopy. The strapped hydrophobic vitamin B₁₂ and a simple hydrophobic vitamin B₁₂ were found to react with (S)-3-bromo-2-methylpropionates more readily than the corresponding R-enantiomers; the highest S-selectivity (75% ee) was observed with the strapped hydrophobic vitamin B₁₂. The S-enantioselectivity was discussed from a stereochemical viewpoint based on the conformational search for the alkylated hydrophobic vitamin B₁₂ by means of molecular mechanics and dynamics calculations.