(8R,9S,13S,14S,17S)-13-methyl-3,17-bis(2-trimethylsilylethoxymethoxy)-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one | 191674-87-0

• 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,17S)-13-methyl-3,17-bis(2-trimethylsilylethoxymethoxy)-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one
• CAS: 191674-87-0
• 化学式: C₃₀H₅₀O₅Si₂
• 分子量: 546.895
• InChiKey: OAYNMBTXYKVEAF-MWNRZKFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.57
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (8R,9S,13S,14S,17S)-13-methyl-3,17-bis(2-trimethylsilylethoxymethoxy)-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one 在 吡啶 、 六甲基磷酰三胺 、 sodium chlorite 、 sodium tetrahydroborate 、 2-甲基-2-丁烯 、 二甲基硫 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hexamethyldisilazane 、 臭氧 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙酸乙酯 、 甲苯 、 叔丁醇 为溶剂， 反应 35.5h， 生成 3,17β-bis(2-trimethylsilyl)ethoxymethyl-7α-(3'-carbomethoxypropyl)estradiol
  参考文献：
  名称：

  A stereoselective synthesis of 7α-(3′-carboxypropyl)estradiol from a noncontrolled substance

  摘要：

  Alkylation of 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-1,3,5(10) estratriene-6-one (2) with 5-bromo-1-pentene using NaHMDS in THF afforded 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-7-alpha-(4'-pentenyl)-1,3,5(10)estratriene-6-one (3) in excellent stereoselectivity (>95% epimeric excess. Functionalization of the side chain in compound 3 was accomplished via ozonolysis, oxidation and esterification to give 5 in 72% yield. The reduction of ester (5) using NaBH4 in MeOH afforded the corresponding 6 alpha-hydroxy compound (6) as a single isomer in 72% yield. The hydroxyl group in 6 was removed by converting to the corresponding xanthate (7) followed by reduction using n-Bu3SnH to afford 8 in good yield. Finally, the SEM protective groups in 8 were removed, after which the ester function was hydrolyzed with LiOH to give 7 alpha-(3'-carboxypropyl)estradiol (10), in 10.6% overall yield from 3. (C) 1997 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(97)00088-3
• 作为产物：
  描述：

  6-酮雌二醇 、 2-(三甲基硅烷基)乙氧甲基氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以84%的产率得到(8R,9S,13S,14S,17S)-13-methyl-3,17-bis(2-trimethylsilylethoxymethoxy)-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one
  参考文献：
  名称：

  6-α-氨基雌二醇的有效立体选择性合成：雌二醇荧光探针的制备。

  摘要：

  将6-氧代雌二醇（2）保护为其双[（2-三甲基甲硅烷基乙氧基）甲基]醚（4），并将其转化为相应的肟（4）。在乙醇中用锌还原后，肟（4）得到96-α-差向异构体过量的6-α-氨基雌二醇（5）的bis-SEM醚。随后，将5用HF以良好的产率水解为6-α-氨基雌二醇（6）。通过NMR确定6中氨基的绝对立体化学，并通过X射线晶体学在相应的4-溴苯甲酰胺衍生物（9）上进行确认。用6-（叔丁氧基羰基氨基）己酸琥珀酰亚胺酯（10）处理胺（6），然后水解产生具有C-6连接基的胺（12）。分别由6和12制备荧光探针（7和13），产率为54-60％，纯度> 99％。

  DOI：

  10.1016/s0039-128x(97)00015-9

文献信息

• Synthesis of 6β-Aminoestradiol and Its Biotin, Acridinium, and Fluorescein Conjugates
  作者：Maciej Adamczyk、Phillip G. Mattingly、Rajarathnam E. Reddy

  DOI：10.1016/s0039-128x(97)00154-2

  日期：1998.3

  Amination of 3,17 beta-Bis[(2-trimethylsilylethoxy)methoxy]-1,3,5(10)-estratriene-6-one (2) using NaCNBH4 and NH(4)OA afforded 3,17-bis(SEM)-6-aminoestradiol (3) as a mixture of alpha and beta-isomers in 60:40 ratio, Hydrolysis of rite mixture of 3 using HF and separation by preparative high-performance liquid chromatography afforded pure 6 beta-aminoestradiol (4) in good yield. The relative stereochemistry of the amino group in 4 was established by NMR. The biotinylated estradiol probe (7), chemiluminescent probe (9), and fluorescent probe (11), were prepared from 6 beta-aminoestradiol (4) and the corresponding biotin, 10-(3-sulfopropyl)-N-tosyl-N-(3-carboxypropyl)acridinium-9-carboxamide and 5-carboxyfluorescein N-succinimidyl esters in 43-63% yields and >99% purity. (C) 1998 by Elsevier Science Inc.
• An efficient stereoselective synthesis of 6-α-aminoestradiol: Preparation of estradiol fluorescent probes
  作者：Maciej Adamczyk、Phillip G. Mattingly、Rajarathnam E. Reddy

  DOI：10.1016/s0039-128x(97)00015-9

  日期：1997.6

  l] ether (4) and converted to the corresponding oxime (4). The oxime (4) on reduction with zinc in ethanol afforded the bis-SEM ether of 6-alpha-aminoestradiol (5) in 96% epimeric excess. Subsequently, 5 was hydrolyzed with HF to 6-alpha-aminoestradiol (6) in good yield. The absolute stereochemistry of the amino group in 6 was established by NMR and confirmed by X-ray crystallography on the corresponding

  将6-氧代雌二醇（2）保护为其双[（2-三甲基甲硅烷基乙氧基）甲基]醚（4），并将其转化为相应的肟（4）。在乙醇中用锌还原后，肟（4）得到96-α-差向异构体过量的6-α-氨基雌二醇（5）的bis-SEM醚。随后，将5用HF以良好的产率水解为6-α-氨基雌二醇（6）。通过NMR确定6中氨基的绝对立体化学，并通过X射线晶体学在相应的4-溴苯甲酰胺衍生物（9）上进行确认。用6-（叔丁氧基羰基氨基）己酸琥珀酰亚胺酯（10）处理胺（6），然后水解产生具有C-6连接基的胺（12）。分别由6和12制备荧光探针（7和13），产率为54-60％，纯度> 99％。
• A stereoselective synthesis of 7α-(3′-carboxypropyl)estradiol from a noncontrolled substance
  作者：Maciej Adamczyk、Donald D. Johnson、Rajarathnam E. Reddy

  DOI：10.1016/s0039-128x(97)00088-3

  日期：1997.12

  Alkylation of 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-1,3,5(10) estratriene-6-one (2) with 5-bromo-1-pentene using NaHMDS in THF afforded 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-7-alpha-(4'-pentenyl)-1,3,5(10)estratriene-6-one (3) in excellent stereoselectivity (>95% epimeric excess. Functionalization of the side chain in compound 3 was accomplished via ozonolysis, oxidation and esterification to give 5 in 72% yield. The reduction of ester (5) using NaBH4 in MeOH afforded the corresponding 6 alpha-hydroxy compound (6) as a single isomer in 72% yield. The hydroxyl group in 6 was removed by converting to the corresponding xanthate (7) followed by reduction using n-Bu3SnH to afford 8 in good yield. Finally, the SEM protective groups in 8 were removed, after which the ester function was hydrolyzed with LiOH to give 7 alpha-(3'-carboxypropyl)estradiol (10), in 10.6% overall yield from 3. (C) 1997 by Elsevier Science Inc.