Process for preparing 24-fluoro-25-hydroxycholecalciferol
AssigneeWisconsin Alumni Research Foundation
InventorsHector F. DeLuca, Yoko Tanaka, Nobuo Ikekawa, Yoshiro Kobayashi
Life of this patent
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Abstract
The invention provides a new derivative of vitamin D.sub.3, 24-fluoro-25-hydroxycholecalciferol. The compound is characterized by vitamin D-like activity in its ability to increase intestinal calcium transport, increase serum calcium and inorganic phosphorous concentration and to prevent the development of rickets. It would find ready application as a substitute for vitamin D.sub.3 and in the treatment of disease states evincing calcium-phosphorous imbalance and which are nonresponsive to vitamin D.sub.3 therapy.
Claims6
24-fluoro-25-hydroxycholecalciferol.
24-fluoro-25-hydroxy previtamin D.sub.3.
Compounds having the formula ##STR2## where each of R and R.sub.1 is hydrogen or acetyl.
Compounds having the formula ##STR3## where each of R and R.sub.1 is acetyl or hydrogen.
Compounds having the formula ##STR4## where R is tetrahydropyranyl, hydrogen, or acyl.
A method for preparing 24-fluoro-25-hydroxycholecalciferol which comprises:
- converting 3-tetrahydropyranyl homocholenic acid ester to its enolate by treatment with lithium dicyclohexylamide and treating the enolate with iodine whereby 3-tetrahydropyranyl-24-iodo-homocholenic acid ester is obtained
- converting said 24-iodo-homocolenic acid ester to 3-tetrahydropyranyloxy-24-hydroxy homocholenic acid by treatment with CF.sub.3 COORAg--Ag.sub.2 O
- reesterifying said 3-tetrahydropyranyloxy-24-hydroxy homocholenic acid with diazomethane to obtain 3-tetrahydropyranyloxy-24-hydroxy homocholenic acid methyl ester and converting said ester to 3-tetrahydropyranyloxy-24-tosyloxy-homocholenic acid methyl ester
- treating said tosylate with potassium fluoride to obtain 3-tetrahydropyranyloxy-24-fluoro-homocholenic acid methyl ester
- hydrolyzing said 3-tetrahydropyranyloxy-24-fluoro-homocholenic acid methyl ester to obtain 24-fluoro-homocholenic acid methyl ester
- treating said ester with a Grignard reagent followed by acetylation to produce 24-fluoro-25-hydroxy-cholesterol 3-acetate
- allylically brominating said cholesterol acetate followed by dehydrobromination and separating 3-acetoxy-24-fluoro-25-hydroxy-5,7-cholestadiene
- saponifying said diene and exposing the resulting 3,25-dihydroxy-24-fluoro-5,7-cholestadiene to actinic radiation whereby 24-fluoro-25-hydroxy previtamin D.sub.3 is obtained
- thermally isomerizing said previtamin and recovering 24-fluoro-25-hydroxy-cholecalciferol.
Dependencies are inferred from the claim text.