Chemical synthesis of the 17-propanamide derivatives of stereoisomeric Δ14-17α- and 17β-estradiols: potential 17β-hydroxysteroid dehydrogenase inhibitors.
The 17-propanamide derivatives of diastereomeric Δ(14)-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 Δ(14)-estrone, (2) Grignard reaction of Δ(14)-estrone with allylmagnesium bromide followed by regioselective hydroboration of the resulting stereoisomeric 17ξ-allyl-Δ(14)-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 NH(3) under positive pressure of H(2).
Department of Chemistry, College of Humanities & Sciences, Nihon University, Setagaya, Sakurajousui, Tokyo, Japan. takaiida@chs.nihon-u.ac.jp
Takashi
T
Iida
Shoujiro
S
Ogawa
Hideyuki
H
Tamegai
Yuuki
Y
Adachi
Hiroaki
H
Saito
Shigeo
S
Ikegawa
Hiroaki
H
Konishi
Akimitsu
A
Takagi
Takeshi
T
Matsuzaki
D000577:Amides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000737:chemistry; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D000577:Amides; D004791:Enzyme Inhibitors; D004970:Estrone; D004958:Estradiol; D006913:Hydroxysteroid Dehydrogenases; C035507:3(17)-hydroxysteroid dehydrogenase