Recent Developments Towards the Synthesis of Vitamin D Metabolites

Abstract

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.

Keywords: Cancer prevention; assay development; review; stereoselective synthesis; vitamin D metabolites.