title: Chemical synthesis of (24R)-24,25-dihydroxy[26,27-3H]vitamin D3 of high specific activity.
abstract: Chemical synthesis of (24R)-24,25-dihydroxy-[26,27-3H]vitamin D3, and its 24-epimer has been devised that allows introduction of 3H at the terminal step of the synthesis. The epimeric mixture is derivatized as the tris(trimethylsilyl) ethers and resolved by high-performance liquid chromatography. The product has a specific activity of 178 Ci/mmol and is fully active in binding to the rat plasma vitamin D binding protein and in the elevation of serum calcium levels of vitamin D deficient rats. The synthesis begins with the readily available 3 beta-hydroxy-5-cholenic acid methyl ester and involves a Pummerer rearrangement, introduction of the delta 7, irradiation, and isolation of the 26,27-dinor-25-carboxylic acid methyl ester of vitamin D3. This compound is then treated with a Grignard reagent containing 3H (80 +/- 10 Ci/mmol).
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D001681:Biological Assay; D002118:Calcium / Q000097:blood; D004100:Dihydroxycholecalciferols / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D007202:Indicators and Reagents; D007536:Isomerism; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D014316:Tritium; D014808:Vitamin D Deficiency / Q000378:metabolism
chemical_list: D004100:Dihydroxycholecalciferols; D007202:Indicators and Reagents; D014316:Tritium; D015650:24,25-Dihydroxyvitamin D 3; D002118:Calcium