3-t-butyldimethylsilyoxy-17-β-(tetrahydro-2H-pyran-2-yl-oxy)-16β-allyl-estra-1,3,5(10)-triene | 220810-51-5

• 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: 3-t-butyldimethylsilyoxy-17-β-(tetrahydro-2H-pyran-2-yl-oxy)-16β-allyl-estra-1,3,5(10)-triene
• 英文别名: tert-butyl-dimethyl-[[(8R,9S,13S,14S,16S,17S)-13-methyl-17-(oxan-2-yloxy)-16-prop-2-enyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl]oxy]silane
• CAS: 220810-51-5
• 化学式: C₃₂H₅₀O₃Si
• 分子量: 510.833
• InChiKey: PKMYJZXFOZVVFY-LXOUNUAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.64
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-t-butyldimethylsilyoxy-17-β-(tetrahydro-2H-pyran-2-yl-oxy)-16β-allyl-estra-1,3,5(10)-triene 在 吡啶 、 sodium hydroxide 、 sodium azide 、 硼烷四氢呋喃络合物 、 四丁基氟化铵 、 双氧水 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(3-hydroxy-17β-(tetrahydro-2H-pyran-2-yl-oxy)-estra-1,3,5(10)-trien-16β-yl)-azidopropane
  参考文献：
  名称：

  Solid-phase synthesis of phenolic steroids: Towards combinatorial libraries of estradiol derivatives

  摘要：

  The 16 beta-(azidopropyl) derivative of estradiol (7) was synthesized and coupled to aminomethyl resin via a photolabile o-nitrobenzyl linker. Condensation of the corresponding iminophosphorane with activated acids successfully gave amides. Photocleavage resulted in good yield recovery of estradiol derivatives 15 and 16 in acceptable purities for biological screening. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)02640-9
• 作为产物：
  描述：

  3-(O-tert-butyl(dimethyl)silyl)estrone 在 甲醇 、 lithium aluminium tetrahydride 、 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 3-t-butyldimethylsilyoxy-17-β-(tetrahydro-2H-pyran-2-yl-oxy)-16β-allyl-estra-1,3,5(10)-triene
  参考文献：
  名称：

  Solid-phase synthesis of phenolic steroids: Towards combinatorial libraries of estradiol derivatives

  摘要：

  The 16 beta-(azidopropyl) derivative of estradiol (7) was synthesized and coupled to aminomethyl resin via a photolabile o-nitrobenzyl linker. Condensation of the corresponding iminophosphorane with activated acids successfully gave amides. Photocleavage resulted in good yield recovery of estradiol derivatives 15 and 16 in acceptable purities for biological screening. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)02640-9

文献信息

• Synthesis of Simplified Hybrid Inhibitors of Type 1 17β-Hydroxysteroid Dehydrogenase via Cross-Metathesis and Sonogashira Coupling Reactions
  作者：Marie Bérubé、Donald Poirier

  DOI：10.1021/ol048820u

  日期：2004.9.1

  text] The inhibitor of type 1 17beta-hydroxysteroid dehydrogenase EM-1745 (1) exhibits affinity for both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding domains. However, to increase its bioavailability, this compound needs to be simplified. The efficient and convergent synthesis of simplified substrate/cofactor hybrid inhibitors (compounds 2) involving a cross-metathesis and a

  [结构：见正文] 1型17β-羟基类固醇脱氢酶EM-1745（1）的抑制剂对底物（雌酮或雌二醇）和辅因子（NAD（P）H）结合域均表现出亲和力。但是，为了提高其生物利用度，需要简化该化合物。描述了涉及交叉复分解和Sonogashira偶联反应的关键步骤的简化底物/辅因子杂化抑制剂（化合物2）的有效和收敛合成。还测试了化合物2a-c作为酶抑制剂，并与EM-1745进行了比较。
• Design, chemical synthesis, and in vitro biological evaluation of simplified estradiol–adenosine hybrids as inhibitors of 17β-hydroxysteroid dehydrogenase type 1
  作者：Marie Bérubé、Donald Poirier

  DOI：10.1139/v09-083

  日期：2009.8

  and the cofactor-binding sites of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). These analogues of potent E2–adenosine hybrid inhibitor EM-1745, where the adenosine moiety was replaced by a more stable benzene derivative, were synthesized from estrone using alkene cross-metathesis and Sonogashira coupling reactions as key steps. In vitro biological evaluation of these steroid derivatives revealed

  一系列雌二醇 (E2) 衍生物被设计为与 17β-羟基类固醇脱氢酶 1 (17β-HSD1) 的底物和辅因子结合位点相互作用。这些有效的 E2-腺苷杂化抑制剂 EM-1745 的类似物，其中腺苷部分被更稳定的苯衍生物取代，是使用烯烃交叉复分解和 Sonogashira 偶联反应作为关键步骤从雌酮合成的。这些类固醇衍生物的体外生物学评估表明，在 E2 的 16β 位和带有羧酸基团的腺苷模拟物之间的 13 个亚甲基间隔物对 17β-HSD1 的抑制作用最好。
• Chemical synthesis of 16β-propylaminoacyl derivatives of estradiol and their inhibitory potency on type 1 17β-hydroxysteroid dehydrogenase and binding affinity on steroid receptors
  作者：Martin R. Tremblay、Sheng-Xiang Lin、Donald Poirier

  DOI：10.1016/s0039-128x(01)00116-7

  日期：2001.11

  The 17 beta -hydroxysteroid dehydrogenases (17 beta -HSDs) are members of a family of enzymes that catalyze the interconversion of weakly active sexual hormones (ketosteroids) and potent hormones (17 beta -hydroxysteroids). Among the known isoforms of 17 beta -HSD, the type I catalyzes the NAD(P)H-mediated reduction of estrone (E-1) to estradiol (E-2), a predominant mitogen for the breast cancer cells. Therefore, the inhibition of this particular enzyme is a logical approach to reduce the concentration of estradiol in breast tumors. To develop inhibitors of type 1 17 beta -HSD activity, we hypothesized that molecules containing both hydrophobic and hydrophilic components should be interesting candidates for interacting with both the steroid binding domain and some amino acid residues of the cofactor binding domain of the enzyme. Firstly, a conveniently protected 16 beta-(3-aminopropyl)-E-2 derivative was synthesized from commercially available E-1. Then, a representative of all class of NHBoc-protected amino acids (basic, acid, aromatic, aliphatic, hydroxylated) were coupled using standard procedures to the amino group of the precursor. Finally, cleavage of all protecting groups was performed in a single step to generate a series of 16 beta -propylaminoacyl derivatives of E-2. The enzymatic screenings revealed that none of the novel compounds can inhibit the reductive activity of type 1 17 beta -HSD. On the other hand, all of these E-2 derivatives did not show any significant binding affinity on four steroid receptors including the estrogen receptor. Additional efforts aimed at improving the inhibitory potency of these steroidal derivatives on type 1 17 beta -HSD without providing estrogenic activities is under investigation using a combinatorial chemistry approach. (C) 2001 Elsevier Science Inc. All rights reserved.