(8R,9S,13S,14S)-3-Bromomethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one | 165609-58-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (8R,9S,13S,14S)-3-Bromomethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one
• 英文别名: (8R,9S,13S,14S)-3-(Bromomethyl)-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one；(8R,9S,13S,14S)-3-(bromomethyl)-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 165609-58-5
• 化学式: C₁₉H₂₃BrO
• 分子量: 347.295
• InChiKey: SKMKBBBFCGSWHT-VXNCWWDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (8R,9S,13S,14S)-3-Bromomethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one 在 对甲苯磺酸 作用下， 以 水 、 丙酮 、 苯 为溶剂， 反应 22.0h， 生成 2-[(8'R,9'S,13'S,14'S)-13'-methylspiro[1,3-dioxolane-2,17'-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene]-3'-yl]acetonitrile
  参考文献：
  名称：

  Synthesis of estrone-3-sulfate analogues bearing novel non-hydrolyzable sulfate mimetics

  摘要：

  Estrone sulfate analogues have been prepared in which the sulfate group has been replaced with an alpha,alpha-difluoromethylenesulfonate or alpha,alpha-difluoromethylenetetrazole group. The key step in these syntheses was the electrophilic fluorination of neopentylsulfonate ester and nitrile intermediates with N-fluorobenzenesulfonimide (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00732-7
• 作为产物：
  描述：

  雌酚酮 在 bis(triphenylphosphine) palladium (Il) acetate 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 硫酸 、 1,3-双(二苯基膦)丙烷 、 溴 、 对甲苯磺酸 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 43.0h， 生成 (8R,9S,13S,14S)-3-Bromomethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  Estrone sulfate analogs as estrone sulfatase inhibitors

  摘要：

  The high serum concentration of estrone sulfate and the presence of estrone sulfatase in breast tumors constitute an important mechanism of local synthesis of estrogens in the tissue. Thus, inhibitors of estrone sulfatase may be effective in the treatment of estrogen-dependent breast cancer. In this study, we synthesized several isostructural analogs of estrone sulfate (estrone-3-methylsulfonate, estrone phosphate, 3-desoxyestradiol-3-methylenesulfonate, and 3-desoxyestrone-3-methylenesulfonate) and tested them on human placental sterylsulfatase. The results were (i) The K-i of 3-desoxyestrone-3-methylenesulfonate 12 and 3-desoxyestradiol-3-methylenesulfonate 7 are more than 100-fold higher than the K-i or K-M estrone sulfate, (ii) As compared to estrone sulfate, the K-i value for estrone-3-methylsulfonate 2 is about 30-fold higher, while estrone phosphate 3 is bound by the sulfatase with roughly the same affinity as estrone sulfate. The results shed some light on the electronical and sterical requirements for high affinity binding to the enzyme.

  DOI：

  10.1016/0039-128x(94)00048-h

文献信息

• Synthesis of a non-hydrolyzable estrone sulfate analogue bearing the difluoromethanesulfonamide group and its evaluation as a steroid sulfatase inhibitor
  作者：Yong Liu、Vanessa Ahmed、Bryan Hill、Scott D. Taylor

  DOI：10.1039/b508852f

  日期：——

  Steroid sulfatase (STS) catalyzes the hydrolyis of steroidal sulfates such as estrone sulfate (ES1) and is considered to be an attractive target in the treatment of steroid dependent cancers. A non-hydrolyzable estrone sulfate (ES1) analogue bearing an α,α-difluorosulfonamide moiety at the 3-position on the A-ring, compound 7, was synthesized. Key to the success of this synthesis was the first use of the allyl group as a sulfonamide protecting group. The pKa of this ES1 mimic in 0.1 M bis-tris propane, 10% DMSO was determined to be 8.05 using 19F NMR. Compound 7 is a reversible inhibitor with a Ki similar to that of its sulfonate analogue at pH 7.0. It is more potent than its nonfluorinated sulfonamide analogue and, its inhibitory potency increases with increasing pH, a trend opposite to that of other STS inhibitors. Possible reasons for this are presented.

  类固醇硫酸酯酶 (STS) 催化类固醇硫酸盐的水解，例如硫酸雌酮 (ES1)，被认为是治疗类固醇依赖性癌症的一个有吸引力的靶标。合成了在 A 环 3 位上带有 α,α-二氟磺酰胺部分的不可水解雌酮硫酸盐 (ES1) 类似物，即化合物 7。该合成成功的关键是首次使用烯丙基作为磺酰胺保护基团。使用 19F NMR 测定此 ES1 模拟物在 0.1 M 双-三丙烷、10% DMSO 中的 pKa 为 8.05。化合物 7 是一种可逆抑制剂，在 pH 7.0 时的 Ki 值与其磺酸盐类似物相似。它比非氟化磺酰胺类似物更有效，并且其抑制效力随着 pH 值的增加而增加，这一趋势与其他 STS 抑制剂相反。提出了可能的原因。
• Synthesis of estrone-3-sulfate analogues bearing novel non-hydrolyzable sulfate mimetics
  作者：Mei-Jin Chen、Scott D. Taylor

  DOI：10.1016/s0040-4039(99)00732-7

  日期：1999.5

  Estrone sulfate analogues have been prepared in which the sulfate group has been replaced with an alpha,alpha-difluoromethylenesulfonate or alpha,alpha-difluoromethylenetetrazole group. The key step in these syntheses was the electrophilic fluorination of neopentylsulfonate ester and nitrile intermediates with N-fluorobenzenesulfonimide (C) 1999 Elsevier Science Ltd. All rights reserved.
• Estrone sulfate analogs as estrone sulfatase inhibitors
  作者：P Li

  DOI：10.1016/0039-128x(94)00048-h

  日期：1995.3

  The high serum concentration of estrone sulfate and the presence of estrone sulfatase in breast tumors constitute an important mechanism of local synthesis of estrogens in the tissue. Thus, inhibitors of estrone sulfatase may be effective in the treatment of estrogen-dependent breast cancer. In this study, we synthesized several isostructural analogs of estrone sulfate (estrone-3-methylsulfonate, estrone phosphate, 3-desoxyestradiol-3-methylenesulfonate, and 3-desoxyestrone-3-methylenesulfonate) and tested them on human placental sterylsulfatase. The results were (i) The K-i of 3-desoxyestrone-3-methylenesulfonate 12 and 3-desoxyestradiol-3-methylenesulfonate 7 are more than 100-fold higher than the K-i or K-M estrone sulfate, (ii) As compared to estrone sulfate, the K-i value for estrone-3-methylsulfonate 2 is about 30-fold higher, while estrone phosphate 3 is bound by the sulfatase with roughly the same affinity as estrone sulfate. The results shed some light on the electronical and sterical requirements for high affinity binding to the enzyme.