Recent Developments Towards the Synthesis of Vitamin D Metabolites

Due to latest advancements in the development of LC-MS/MS based assays and their applications in clinical chemistry, low abundant vitamin D metabolites can be detected at low concentration with high specificity. Consequently, there is a growing need for their synthesis as stable isotopically labeled compounds to be used as calibration and reference standards. Most commonly, ex chiral pool synthesis, starting with vitamin D2, and palladium(0) catalyzed coupling reactions are applied in vitamin D synthesis. By contrast, little is known so far regarding the application of cobalt complexes for this purpose. In fact, the Pausen-Khand reaction can be applied for the synthesis of a wide range of isotopically labeled vitamin D metabolites that are hardly accessible by other known methods. Applications, scope and limitations of the most recent vitamin D synthesis methods, with a particular focus on this new promising methodology using Co-complexes, are discussed.