2-[4-[Tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl methanesulfonate | 203250-11-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2-[4-[Tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl methanesulfonate
• CAS: 203250-11-7
• 化学式: C₄₂H₄₈O₆SSi
• 分子量: 708.991
• InChiKey: JAMHDEXZONIQAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.32
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[4-[Tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl methanesulfonate 在 吡啶 、 亚磷酸三苯酯 、 potassium tert-butylate 、 四丁基氟化铵 、 溴 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4-[1-(2-{3-bromo-1-[(triphenylmethoxy)methyl]propoxy}ethyl)indol-3-yl]-3-(indol-3-yl)-3-pyrroline-2,5-dione
  参考文献：
  名称：

  Cyclization Strategies for the Synthesis of Macrocyclic Bisindolylmaleimides

  摘要：

  Three new approaches to the synthesis of macrocyclic bisindolylmaleimides 1-4 have been identified. Two strategies afford 8, the penultimate intermediate for the synthesis of 1-4, in 73% and 32% yield by intramolecular cyclization of 31 and 40, respectively. The optimum synthesis of 1 was achieved in nine steps and 15% yield by intramolecular formation of the macrocycle and maleimide in one step by reaction of the sodium indolate of 12 with methyl indole-3-glyoxylate 47. The mechanism of this reaction has been elucidated, using the trityl-protected derivative, to involve initial formation of the tricarbonyl im ide 48, followed by irreversible alkylation of the indole nitrogen to generate the 17-membered macrocycle 49. Cyclization of 49 to hydroxymaleimide 50 and subsequent dehydration afforded 8a. This approach eliminated the problem of dimerization observed in the intramolecular cyclization reactions.

  DOI：

  10.1021/jo001605g
• 作为产物：
  描述：

  2-[3-(tert-Butyl-diphenyl-silanyloxy)-1-trityloxymethyl-propoxy]-ethanol 以91的产率得到2-[4-[Tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl methanesulfonate
  参考文献：
  名称：

  Synthesis of bisindolylmaleimides

  摘要：

  本发明提供了一种新型合成式(I)化合物的方法：##STR1## 该化合物的产率高且不需要使用昂贵的色谱分离。该合成方法尤其有优势，因为它是立体选择性的。

  公开号：

  US05541347A1

文献信息

• Synthesis of bisindolylmaleimides
  申请人：Eli Lilly and Company

  公开号：US05541347A1

  公开（公告）日：1996-07-30

  The present invention provides a novel synthesis of the compounds of Formula (I): ##STR1## The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereoselective.

  本发明提供了一种新型合成式(I)化合物的方法：##STR1## 该化合物的产率高且不需要使用昂贵的色谱分离。该合成方法尤其有优势，因为它是立体选择性的。
• Macrocyclic Bisindolylmaleimides:  Synthesis by Inter- and Intramolecular Alkylation
  作者：Margaret M. Faul、Leonard L. Winneroski、Christine A. Krumrich、Kevin A. Sullivan、James R. Gillig、David A. Neel、Christopher J. Rito、Michael R. Jirousek

  DOI：10.1021/jo971980h

  日期：1998.3.1

  Macrocyclic bisindolylmaleimides 1-4 have been identified as competitive reversible inhibitors of PKC beta(1) and beta(2) and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1-4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active compound, proceeds in 11 steps and 26% overall yield (>98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1-4 by intramolecular alkylation proved less efficient, requiring 1? steps and affording 1-4 in lower overall yields of 6.0-8.5%.
• J. Med. Chem. 1996, 39, 2664-2671
  作者：

  DOI：——

  日期：——
• Cyclization Strategies for the Synthesis of Macrocyclic Bisindolylmaleimides
  作者：Margaret M. Faul、Christine A. Krumrich

  DOI：10.1021/jo001605g

  日期：2001.3.1

  Three new approaches to the synthesis of macrocyclic bisindolylmaleimides 1-4 have been identified. Two strategies afford 8, the penultimate intermediate for the synthesis of 1-4, in 73% and 32% yield by intramolecular cyclization of 31 and 40, respectively. The optimum synthesis of 1 was achieved in nine steps and 15% yield by intramolecular formation of the macrocycle and maleimide in one step by reaction of the sodium indolate of 12 with methyl indole-3-glyoxylate 47. The mechanism of this reaction has been elucidated, using the trityl-protected derivative, to involve initial formation of the tricarbonyl im ide 48, followed by irreversible alkylation of the indole nitrogen to generate the 17-membered macrocycle 49. Cyclization of 49 to hydroxymaleimide 50 and subsequent dehydration afforded 8a. This approach eliminated the problem of dimerization observed in the intramolecular cyclization reactions.
• J. Org. Chem. 1998, 63, 1961-1973
  作者：

  DOI：——

  日期：——