Efficient synthesis of 3-TBDMS-11α,25-dihydroxyvitamin D3 and D2 ethers

Abstract

Vitamin D deficiency might cause a wide variety of human disorders. As a prerequisite for appropriate diagnosis and therapy, medicinally relevant vitamin D metabolites have to be assayed most accurately and with high specificity. It has been demonstrated, that vitamin D conjugates, linked via a hydroxyl group at C11, might be promising for the development of highly specific antibodies to be employed in competitive protein binding assays. The connective synthesis of 3-TBDMS-11α,25-dihydroxyvitamin D₃ and D₂ ethers in 500 mg scale, starting from vitamin D₂, is described. For installation of a hydroxyl group at C11 a sequence of Pd(OAc)₂ mediated oxidation of an enone, epoxidation and subsequent epoxide ring opening was applied to obtain a suitable CD-ring precursor, that was connected with an A-ring diphenylphosphine oxide by Wittig-Horner reaction. Finally, an appropriate side chain was installed, respectively.

Keywords: Assay development; Biomarkers; ELISA; Protein binding assays; Vitamin D deficiency; Vitamin D metabolites; Vitamin D related diseases; Vitamin D synthesis.