Functionalisation of vitamin B 12 derivatives with a cobalt β-phenyl ligand boosters antimetabolite activity in bacteria.

This study describes the syntheses of four singly- and two doubly-modified vitamin B 12 derivatives for generating antimetabolites of Lactobacillus delbrueckii ( L. delbrueckii ). The two most potent antagonists, a Co β -phenyl-cobalamin- c ,8-lactam and a 10-bromo-Co β -phenylcobalamin combine a c -lactam or 10-bromo modification at the "eastern" site of the corrin ring with an artificial organometallic phenyl group instead of a cyano ligand at the β-site of the cobalt center. These two doubly-modified B 12 antagonists (10 nM) inhibit fully B 12 -dependent (0.1 nM) growth of L. delbrueckii . In contrast to potent 10-bromo-Co β -phenylcobalamin, single modified 10-bromo-Co β -cyanocobalamin lacking the artificial organometallic phenyl ligand does not show any inhibitory effect. These results suggest, that the organometallic β-phenyl ligand at the Co center ultimately steers the metabolic effect of the 10-bromo-analogue.