An efficient synthesis of 1α,25-dihydroxyvitamin D3LC-biotin.
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 D3LC-biotin) is employed for measurement of actual calicitriol concentration. A new efficient synthesis of 1α,25-dihydroxyvitamin D3LC-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 D3and D2derivatives.
Endotherm Life Science Molecules, 66123 Saarbrücken, Germany. Electronic address: lars.kattner@endotherm.de.
Lars
L
Kattner
Endotherm Life Science Molecules, 66123 Saarbrücken, Germany. Electronic address: dan.bernardi@endotherm.de.
Dan
D
Bernardi
D000478:Alkylation; D001710:Biotin / Q000138:chemical synthesis* / Q000737:chemistry; D002117:Calcitriol / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D004872:Ergocalciferols / Q000138:chemical synthesis / Q000737:chemistry
D004872:Ergocalciferols; D001710:Biotin; D002117:Calcitriol
Assay development; Biomarkers; Calcitriol; ELISA; Protein binding assays; Vitamin D deficiency; Vitamin D metabolites; Vitamin D related diseases