3-(3-hydroxy-17β-(tetrahydro-2H-pyran-2-yl-oxy)-estra-1,3,5(10)-trien-16β-yl)-azidopropane | 220810-54-8

• 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-(3-hydroxy-17β-(tetrahydro-2H-pyran-2-yl-oxy)-estra-1,3,5(10)-trien-16β-yl)-azidopropane
• 英文别名: (8R,9S,13S,14S,16S,17S)-16-(3-azidopropyl)-13-methyl-17-(oxan-2-yloxy)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-ol
• CAS: 220810-54-8
• 化学式: C₂₆H₃₇N₃O₃
• 分子量: 439.598
• InChiKey: ZLTVUGZATBZMJK-ONUHZPAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3-hydroxy-17β-(tetrahydro-2H-pyran-2-yl-oxy)-estra-1,3,5(10)-trien-16β-yl)-azidopropane 在 盐酸 、 lithium hydroxide 、 三丁基膦 、 碳酸二异丙酯 、 aminomethyl resin 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 N-[3-[(8R,9S,13S,14S,16S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]propyl]propanamide
  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 吡啶 、 甲醇 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 sodium azide 、 硼烷四氢呋喃络合物 、 四丁基氟化铵 、 双氧水 、 对甲苯磺酸 、 lithium diisopropyl amide 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

文献信息

• Preparation of 16β-Estradiol Derivative Libraries as Bisubstrate Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 Using the Multidetachable Sulfamate Linker
  作者：Marie Bérubé、Florian Delagoutte、Donald Poirier

  DOI：10.3390/molecules15031590

  日期：——

  Finally, after a nucleophilic cleavage, libraries of 30, 63 and 25 estradiol derivatives were provided. A library of 30 sulfamoylated estradiol derivatives was also generated by acidic cleavage and its members were screened for inhibition of steroid sulfatase. Biological evaluation on homogenated HEK-293 cells overexpressing 17β-HSD1 of the estradiol derivatives carrying different oligoamide-type chains

  组合化学是一种强大的工具，用于快速生成大量具有潜在生物活性的化合物。为了开发与底物（雌酮或雌二醇）和辅因子（NAD（P）H）结合位点相互作用的 17β-羟基类固醇脱氢酶 1（17β-HSD1）的双底物抑制剂，我们使用平行固相合成制备三个具有两个或三个分子多样性水平的 16β-雌二醇衍生物文库。我们首先从雌酮合成了一种氨基磺酸酯前体，我们使用我们实验室最近开发的高效多可分离氨基磺酸酯接头策略将其加载到三苯甲基氯树脂上。然后，我们通过 Fmoc 肽化学在类固醇核上引入了分子多样性 [一个或两个氨基酸，然后是一个羧酸]。最后，经过亲核裂解后，提供了 30、63 和 25 种雌二醇衍生物的库。还通过酸裂解生成了 30 种氨磺酰化雌二醇衍生物文库，并筛选了其成员对类固醇硫酸酯酶的抑制作用。对在 C-16 处过表达携带不同寡酰胺型链的雌二醇衍生物 17β-HSD1 的匀浆 HEK-293 细胞的生物学
• A multidetachable sulfamate linker successfully used in a solid-Phase strategy to generate libraries of sulfamate and phenol derivatives
  作者：Donald Poirier、Liviu C. Ciobanu、Marie Bérubé

  DOI：10.1016/s0960-894x(02)00637-6

  日期：2002.10

  The sulfamates and phenols constitute two families of compounds with numerous interesting biological properties. Using the ability of a new multidetachable sulfamate linker to generate these two families of compounds from the same resin, we designed and synthesized libraries of estradiol derivatives, sulfamoylated or not. A C-16beta side chain was then judiciously diversified to target two key steroidogenic enzymes, the steroid sulfates and the type 1 17beta-HSD. Four libraries of sulfamate and phenol derivatives were easily obtained by solid-phase parallel synthesis in good crude overall yields (13-62%) and HPLC purities (85-96%). Such strategy using the new two-in-line sulfamate linker could be also extended to other therapeutic targets than steroidogenic enzymes, thus adding to its potential. (C) 2002 Elsevier Science Ltd. All rights reserved.