A novel approach to an A-ring synthon for Pd-catalyzed synthesis of 1α-hydroxylated vitamin D metabolites is described. Key step is an asymmetric glyoxylate ene reaction to access a highly diastereomerically pure α-hydroxy ester. Subsequent stereospecific transformation to an anti-1,3-diol and appropriate chemical modifications at both ends of the acyclic precursor leads to a diastereomerically and enantiomerically pure silylated anti-1,3-diol enyne, serving as a versatile A-ring synthon for its use in vitamin D synthesis.
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View Article and Find Full Text PDFNovel approach to A-ring synthon for Pd-catalyzed synthesis of 1α-hydroxylated vitamin D metabolites.
J Steroid Biochem Mol Biol
October 2022
Endotherm Life Science Molecules, 66123 Saarbruecken, Germany. Electronic address:
A novel approach to an A-ring synthon for Pd-catalyzed synthesis of 1α-hydroxylated vitamin D metabolites is described. Key step is an asymmetric glyoxylate ene reaction to access a highly diastereomerically pure α-hydroxy ester. Subsequent stereospecific transformation to an anti-1,3-diol and appropriate chemical modifications at both ends of the acyclic precursor leads to a diastereomerically and enantiomerically pure silylated anti-1,3-diol enyne, serving as a versatile A-ring synthon for its use in vitamin D synthesis.
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Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
Blood levels of the vitamin D (D) metabolites 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D, and 1α,25-dihydroxyvitamin D (1,25(OH)D) are recognized indicators for the diagnosis of bone metabolism-related diseases, D deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D metabolites, such as 20-hydroxyvitamin D and lactone D, also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum. Here, we describe a versatile synthesis of deuterium-labeled D metabolites using A-ring synthons containing three deuterium atoms.
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