3-hydroxymethylestra-1,3,5-(10)-triene-17-one | 165609-57-4

• 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: 3-hydroxymethylestra-1,3,5-(10)-triene-17-one
• 英文别名: 3-methylenehydroxy-estra-1,3,5(10)-trien-17-one；3-hydroxymethylestra-1,3,5(10)-trien-17-one；(8R,9S,13S,14S)-3-(hydroxymethyl)-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 165609-57-4
• 化学式: C₁₉H₂₄O₂
• 分子量: 284.398
• InChiKey: CUWQAYNNRUMVQO-VXNCWWDNSA-N

物化性质

• 熔点：
  153-154 °C
• 沸点：
  457.6±45.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-hydroxymethylestra-1,3,5-(10)-triene-17-one 在 溴 、 对甲苯磺酸 、 三苯基膦 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 4.0h， 生成 (8'R,9'S,13'S,14'S)-3'-(bromomethyl)-13'-methylspiro[1,3-dioxolane-2,17'-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene]
  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 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 lithium aluminium tetrahydride 、 potassium acetate 、 palladium diacetate 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 10.0h， 生成 3-hydroxymethylestra-1,3,5-(10)-triene-17-one
  参考文献：
  名称：

  使用鏻盐的镍催化还原 Csp2-Csp3 交叉偶联

  摘要：

  镍催化与鏻盐和烯丙基 C(sp 3 )-O 键亲电试剂的还原交叉偶联，可直接构建 C(sp 2 )-C(sp 3 ) 键。该协议具有广泛的底物范围、高官能团耐受性和杂环兼容性。值得注意的是，更具挑战性的与杂环噻唑鏻盐的还原交叉偶联也首次实现。

  DOI：

  10.1021/acs.orglett.1c02893

文献信息

• 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.
• Inhibition of steroid sulfatase with 4-substituted estrone and estradiol derivatives
  作者：Chau-Minh Phan、Yong Liu、Byoung-moo Kim、Yaser Mostafa、Scott D. Taylor

  DOI：10.1016/j.bmc.2011.08.046

  日期：2011.10

  Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast cancer. We previously demonstrated that 4-formyl estrone is a time- and concentration-dependent inhibitor of STS. We have prepared a series of 4-formylated estrogens and examined them as irreversible STS inhibitors. Introducing a formyl, bromo or nitro group at the 2-position of 4-formylestrone resulted in loss of concentration and time-dependent inhibition and a considerable decrease in binding affinity. An estradiol derivative bearing a formyl group at the 4-position and a benzyl group at the 17 beta-position yielded a potent concentration and time-dependent STS inhibitor with a K-l of 85 nM and a k(inact) of 0.021 min(-1) (k(inact)/K-l of 2.3 x 10(5) M-1 min(-1)). Studies with estrone or estradiol substituted at the 4-position with groups other than a formyl group revealed that good reversible inhibitors can be obtained by introducing small electron withdrawing groups at this position. An estradiol derivative with fluorine at the 4-position and a benzyl group at the 17 beta-position yielded a potent, reversible inhibitor of STS with an IC50 of 40 nM. The introduction of relatively small electron withdrawing groups at the 4-position of estrogens and their derivatives may prove to be a general approach to enhancing the potency of estrogen-derived STS inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of New Estrone Derivatives Using Excess Oxalyl Chloride
  作者：L. Nahar、S. D. Sarker、P. K. Li、A. B. Turner

  DOI：10.1023/b:conc.0000025465.76505.33

  日期：2004.1

  The synthesis and structure elucidation of three new estrone derivatives chloro-oxo-acetic acid (estra-1,3,5(10)-trien-17-on-3-yl methyl) ester (2), oxalic acid mono (estra-1,3,5(10)-trien-17-on-3-yl methyl) ester (3), and ethyl (3-methoxyestra-1,3,5(10)-trien)-17beta-yl oxalate (5) have been described.