Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis

Abstract

Blood levels of the vitamin D3 (D3) metabolites 25-hydroxyvitamin D3 (25(OH)D3), 24R,25-dihydroxyvitamin D3, and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) are recognized indicators for the diagnosis of bone metabolism-related diseases, D3 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 D3 metabolites, such as 20-hydroxyvitamin D3 and lactone D3, 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 D3 metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D3 (2), 25(OH)D3-23,26-lactone (6), and 1,25(OH)2D3-23,26-lactone (7) were synthesized, and successfully applied as internal standards for the measurement of these compounds in pooled human serum. This is the first quantification of 1,25(OH)2D3-23,26-lactone (7) in human serum.

Synthesis and Chiroptical Properties of a Chiral Isotopologue of syn-Cryptophane-B

“…2 In total synthesis, deuterium-labeled compounds have been used to modify the reaction selectivity. 3 H/D substitution plays also a major role in the development of new drugs and it serves, for instance, to increase their metabolic stability. 4 Interestingly, H/D substitution has also been reported to transform an achiral molecule into a chiral one.…”

Natural Products Chemistry: Advances in Synthetic, Analytical and Bioactivity Studies

“…More in detail, Nagata et al described the synthesis of deuterium-labelled vitamin D analogues with applications in the field of analytical chemistry [ 2 ]. Guo et al studied the derivatives of docosahexaenoic acid as candidates for the treatment of ovarian injury in vivo [ 3 ].…”