Synthetic Approaches toward Vitamin B12 Conjugates

Abstract

AbstractThe ability to conjugate functional molecules to vitamin B12 (cobalamin) is an important strategy for the construction of hybrid molecules with various applications in medicinal chemistry, diagnostics, and biological sciences. Cobalamin, as an exogenous compound, reaches mammalian cells via a system of transport proteins and therefore the position of conjugation must be selected in such a way that the recognition process is not disturbed. The complex structure of vitamin B12 provides many routes for the synthesis of conjugates containing cargos appended at different sites, however, only the e‐propionamide chain, β‐axial position and R5′‐OH are found to meet the aforementioned criteria. Over the years, a number of synthetic approaches leading to cobalamin conjugates have been developed and, herein, we summarize those leading to conjugates with a cargo tethered at the central cobalt ion, macrocyclic core, ribonucleotide moiety, or a combination thereof.