Chemical synthesis of the 17-propanamide derivatives of stereoisomeric Δ¹⁴-17α- and 17β-estradiols: potential 17β-hydroxysteroid dehydrogenase inhibitors

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• 作者：Takashi Iida^a ; ^{takaiida@chs.nihon-u.ac.jp} ; Shoujiro Ogawa^a ; Hideyuki Tamegai^a ; Yuuki Adachi^a ; Hiroaki Saito^b ; Shigeo Ikegawa^c ; Hiroaki Konishi^d ; Akimitsu Takagi^d ; Takeshi Matsuzaki^d
• 关键词：Steroid ; Estrogen ; Estradiol ; Estrone ; Chemical synthesis ; Spiro-γ ; -lactone ; Propanamide ; NMR ; 17&#x3b2 ; -HSD ; Inhibitor
• 刊名：Chemistry and Physics of Lipids
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：164
• 期：2
• 页码：106-112
• 全文大小：255 K

文摘

The 17-propanamide derivatives of diastereomeric Δ¹⁴-17α- and 17β-estradiols, the potential candidates of a 17β-hydroxysteroid dehydrogenase (17β-HSD) inhibitor, were synthesized in 11 steps from estrone. The principal reactions employed involved in (1) conversion of estrone to the corresponding Δ¹⁴-estrone, (2) Grignard reaction of Δ¹⁴-estrone with allylmagnesium bromide followed by regioselective hydroboration of the resulting stereoisomeric 17ξ-allyl-Δ¹⁴-17ξ-ols with 9-borabicyclo[3.3.1]nonane (9-BBN), and (3) direct amidation of the 17ξ-O-/17ξ-C-spiro-γ-lactones with NH₃ under positive pressure of H₂.