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DOI: 10.1039/A604405K (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1997, 1895-1904

19-Hydroxy-5β,19-cyclosteroids: synthesis, isomerization and ring opening

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John F. Templeton, Yangzhi Ling, Weiyang Lin, Helena Majgier-Baranowska and Kirk Marat

Abstract

19(R/S)-Hydroxy-5β,19-cyclosteroids have been synthesised from the 19-formyl 4-en-3-one by reductive cyclization with zinc in aqueous acetic acid. Treatment of the aldehyde with lithium in liquid ammonia also gave the 19(R)-hydroxy-5β,19-cyclosteroid together with the 17β-hydroxy analogue. The 19(R)-alcohol is isomerized to the 19(S)-alcohol in either dilute acidic or basic media via the 3-hydroxy-3,5-cyclosteroid. The 19(S)-alcohol is in equilibrium with its 3-hemiketal. Treatment of the 19(R)-alcohol with methanolic HCl gave the 19(R)- and 19(S)-methyl ethers, the 3-methyl ether 19-ketal and the 3α-methoxy-3β,5β- cyclosteroid. Further rearrangements of the 19(R)- and 19(S)-alcohols take place on more vigorous treatment with acid or base to give cyclopropanol ring-opened aldehydes including a 5β-methyl-A-norsteroid. Metal hydride reduction of the 3-ketone in the 19(R)-alcohol gave only the 3β-alcohol whereas the 19(S)-alcohol gave both the 3α- and 3β-alcohols. Acid treatment of the 3β-alcohols gave products with retention of configuration at C-5 and C-19 while base-catalysed ring opening gave inversion at C-5. Ring opening mainly involved breaking of the 5,19-bond, however, the 19(S)-alcohol also resulted in 10,19-bond cleavage. Structures were established by NMR measurements.

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