Inhibitors of sterol synthesis. An improved chemical synthesis of 26-oxygenated Δ8(14)-15-ketosterols having the 25R configuration

✍ Scribed by Abdul U. Siddiqui; William K. Wilson; George J. Schroepfer Jr.

• Book ID: 103037115
• Publisher: Elsevier Science
• Year: 1994
• Tongue: English
• Weight: 879 KB
• Volume: 71
• Category: Article
• ISSN: 0009-3084
• DOI: 10.1016/0009-3084(94)90072-8

✦ Synopsis

25R)-3/3,26-Dihydroxy-5c~-cholest-8( 14)-en-15-one (1) was synthesized in four steps from (25R)-3/3,26-diacetoxycholesta-5,7-diene (111) in 30% overall yield, lsomerization of 111 with HCI in chloroform-dichloromethane at -60°C gave (25R)-3/3,26-diacetoxy-5et-cholesta-7,14-diene together with the 5u-A 8'14 and 5/3-A 8't4 isomers in a 5:1:1 ratio. Epoxidation of the crude diene mixture with m-chloroperbenzoic acid, followed by hydrolysis in acetone containing concentrated HC104 (0.1%) gave (25R)-3/3,26-diacetoxy-5u-cholest-8( 14)-en-15-one (VIII), accompanied by numerous minor byproducts, including the 5u, 14/3-A7, 5c~, 14/3-A8 and 5/3,14/~-A8 isomers of VIII. All four 15-ketosterol esters were isolated by chromatography and fully characterized by mass spectrometry and tH and ~SC nuclear magnetic resonance. Treatment of VIII with potassium carbonate in degassed methanol gave 1.