Synthesis of 15β-hydroxy-24-oxocholesterol and 15β,29-dihydroxy-7-oxofucosterol

Abstract

3β-Acetoxyandrost-5-en-17-one has been converted into 15β-hydroxy-24-oxocholesterol. Reaction of (17E)-3β-(dimethyl-t-butylsilyloxy)-15β,16β-epoxypregna-5,17(20)-diene with the magnesium cyanocuprate derivative of 3-(1,3-dioxolan-2-yl)-4-methylpentyl bromide gave (20R)-3β-(dimethylt-butylsilyloxy)-15β-hydroxy-24-oxocholesta-5,16-diene 24-ethylene acetal in 80% yield, and this was converted into the target compound in high yield by catalytic hydrogenation followed by removal of the protecting groups. Reaction of 3β,15β-diacetoxycholest-5-en-24-one with the anion of diethyl cyanomethylphosphonate and reduction of the resulting nitrite with DIBAL-H, gave 15β,29-dihydroxyfucosterol. This was converted into the 3,29-diacetate 15-formate and oxidized with chromium trioxide–3,5-dimethylpyrazole. Removal of the acetate and formate groups with aqueous potassium carbonate afforded 15β,29-dihydroxy-7-oxofucosterol.