3962-66-1Relevant academic research and scientific papers
Preparation 19-nor -5 (10)-androstene ketone compound method
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, (2017/01/12)
The invention discloses a method for preparing a 19-Norandrost-5(10)-ene-3,17-dione compound. The method comprises the steps of by taking estrone as an ingredient, firstly sequentially performing etherification reaction, ketal protection reaction and birch reduction reaction to obtain a birch reduction product; then by taking lower fatty acid as a catalyst, performing selective hydrolysis reaction on the birch reduction product to produce the 19-Norandrost-5(10)-ene-3,17-dione compound. According to the method, the hydrolysis technology of the birch reduction product containing 17-bit ketal protecting group is optimized and improved, and the single 19-Norandrost-5(10)-ene-3,17-dione with high yield and high selectivity can be obtained through selective hydrolysis reaction by taking binary fatty acid as an acid catalyst for the first time; in addition, the fact that the 17-bit ketal protecting derivatives of the single 19-Norandrost-5(10)-ene-3,17-dione compound can be obtained by taking lower unitary fatty acid as a catalyst is found for the first time.
19-hydroxy-5β,19-cyclosteroids: Synthesis, isomerization and ring opening
Templeton, John F.,Ling, Yangzhi,Lin, Weiyang,Majgier-Baranowska, Helena,Marat, Kirk
, p. 1895 - 1904 (2007/10/03)
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.
Novel Insertion, Rearrangement and Addition Products from Dihalogenocarbene Reactions with 5(10)-Unsaturated Steroids
Templeton, John F.,Ling, Yangzhi,Lin, Weiyang,Pitura, Randy J.,Marat, Kirk,Bridson, John N.
, p. 1149 - 1158 (2007/10/02)
Novel insertion, rearrangement and addition products from dibromocarbene and dichlorocarbene reactions with 5(10)-unsaturated steroids have been identified.The dihalogenocarbenes were prepared under phase-transfer conditions (CHBr3- or CHCl3-NaOH), and from CHBr3-KOBut-Et2O, phenyl(trichloromethyl)mercury and sodium trichloroacetate.Evidence that the major products arise from an initial dihalogenocarbene reaction on the α face of the molecule is reported.The major products obtained from addition of CBr2 to 3,17-disubstituted estr-5(10)-enes, after ketal hydrolysis, were 19(S)-bromo-9α,19-cyclo-10α-androst-4-en-3-one and 3',3',19(S)-tribromo-3'H-9α,19-cyclopropa-5β,10α-androstan-3-one derivatives together with the 19,19-dibromo-5α,19-cyclo-10α-steroid adduct.No products from addition of CBr2 to the β-face of the double bond, as previously reported, were identified.Reactions of CCl2 gave, besides rearrangement products analogous to those obtained from CBr2, a 5α-hydroxy-9α,19α-cycloandrostane derivative, the 9α-CHCl2 insertion derivative and both α- and β-face addition products to the double bond.Structures were established by homonuclear and heteronuclear correlation and nuclear Overhauser effect NMR measurements and X-ray crystallography.
Biosynthesis of Estrogens. Estr-5(10)-ene-3,17-dione: Isolation, Metabolism and Mechanistic Implications
Ranjith, H.,Dharmaratne, W.,Kilgore, James L.,Roitman, Esther,Shackleton, Cedric,Caspi, Eliahu
, p. 1529 - 1536 (2007/10/02)
The 16-2H2 title compound 5b constituted a significant amount of the non-aromatic metabolites recovered from incubations of 3,17-dioxo-2H3>androst-4-en-19-al 1 with placental aromatase.For the evaluation of the role of compound 5b in the elaboration of estrogens, its transformations at pH 6.5 and 7.2 in the presence and absence of microsomal placental aromatase were investigated.In the presence of the aromatase at pH 6.5, estrogens (6.8percent), products of isomerization of the double bond (Δ5(10) -> Δ4) and products of reduction of the carbonyl groups were formed.When the incubation was carried out at pH 7.2, products similar to those obtained above were isolated but in different yields.Noticeably more estrogens (22.7percent) and less of the reduced products were formed.Additionally, at pH 7.2, 10β-hydroxy-2H2>estr-4-ene-3,17-dione 4a was obtained.In the absence of the aromatase, which was replaced with bovine albumin at both pH 6.5 and 7.2, 2H2>estr-4-ene-3,17-dione 3a and its 10β-hydroxy derivative 4a were formed in large amounts and were the only products detected.The ramifications of our observations in the context of estrogen biosynthesis are discussed.
Suicide inhibitors of aromatase
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, (2008/06/13)
Thiol-substituted synthetic steriod hormones or androgens having a testosterone ring system backbone are used to inhibit aromatase''s catalyzed conversion of C 19 androgens having a A 4,3-ketone group to estrogens in the treatment of estrogen-dependent tumors, such as metastatic breast cancer in postmenopausal females.The compounds have the general formula: STR1 wherein R 1 =a thiol, such as --SH or --CH 2 SH, and R 2 =OH or =O. The preferred synthetic hormones are 17β-hydroxy-10β-mercaptoestr-4-en-3-one, 19-mercaptoandrost-4-en-3,17-dione, and 10β-mercaptoandrost-4-en-3,17-dione.
