合成路线1

The intermediate 16alpha,17alpha-((R)-butylidenedioxy)-6alpha,9alpha-difluoro-11beta,21-dihydroxypregn-4-ene-3,20-dione (V) has been obtained in several related ways: 1. The selective reduction of 6alpha, 9alpha-difluoro-16alpha-prednisolone (I) with H2 over tris(triphenylphosphine)rhodium chloride catalyst in ethanol gives 6alpha,9alpha-difluoro-11beta,16alpha,17alpha,21-tetrahydroxypregn-4-ene-3,20-dione (II), which is cyclized with butanal (III) catalyzed by HClO4 in dioxane to yield the butylidenedioxy derivative (IV) as a diastereomeric mixture. Finally, the desired (R)-diastereomer, the intermediate (V), is separated by column chromatography over Sephadex LH-20. 2. The selective reduction of 16alpha,17alpha-((R)-butylidenedioxy)-6alpha,9alpha-difluoro-11beta,21-dihydroxypregna-1,4-diene-3,20-dione (VI) with H2 over tris(triphenylphosphine)rhodium chloride catalyst in ethanol also yields intermediate (V). 3. The selective reduction of fluocinolone acetonide (VII) with H2 over tris(triphenylphosphine)rhodium chloride catalyst in ethanol gives 6alpha,9alpha-difluoro-11beta,21-dihydroxy-16alpha,17alpha-(isopropylidenedioxy)pregen-4-ene-3,20-dione (VIII), which is then treated with butanal (III) and HClO4 over SiO2 in heptane to afford intermediate (V). The target compound is finally obtained by esterification of intermediate (V) with hexadecanoyl chloride (IX) in pyridine.