5′-Vitamin B12 derivatives suitable for bioconjugation via the amide bond

Vitamin B-12 is an attractive candidate for a drug or an imaging-agent carrier into cells, due to its dietary uptake and well established transport through glycoproteins. Utilization of this system requires an appropriate functionalization of vitamin B-12 that both allows for the conjugation of therapeutics and does not interrupt its recognition by transport proteins. Modifications at the 5'-position on the ribose moiety are among a few approaches which meet the criteria. In this article we present vitamin B-12 derivatives bearing either the amino or the carboxylic group at the 5'-position. The presence of these functional groups enables conjugation of biologically important molecules to vitamin B-12 via the amide bond. The established method is not only limited to organic media but also works in an aqueous environment, giving the desired products in very good yields.