An Efficient Synthesis of 1α,25-Dihydroxyvitamin D3 LC-Biotin

Publication date: Available online 6 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Lars Kattner, Dan Bernardi
In recent years the apparent impact of vitamin D deficiency on human health has gained increased awareness. Consequently, the development of appropriate assays to measure the status of medicinally most relevant vitamin D metabolites in human blood, serum or relevant tissue is continuously being improved. Particularly, assaying of 1α,25-dihydroxyvitamin D3, in turn considered as the most active metabolite, is mainly indicated in disorders leading to calcaemia or those resulting from an impaired 1α-hydroxylation of 25-hydroxyvitamin D3. Thus, in some competitive protein binding and ELISA assays, biotin-linked 1α,25-dihydroxyvitamin D3 (1α,25-dihydroxyvitamin D3 LC-biotin) is employed for measurement of actual calicitriol concentration. A new efficient synthesis of 1α,25-dihydroxyvitamin D3 LC-biotin is described, starting with readily available vitamin D2, and combining a classical approach to access 1α,25-dihydroxyvitamin D3, appropriate OH-protective group transformations, and a C-3-O-alkylation, suitable to connect the biotin-linker in a reliable, selective and high yielding strategy. The developed methodology is applicable to the synthesis of a wide variety of C-3-OH-linked vitamin D3 and D2 derivatives.



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