(S)-4-(triphenylmethoxy)-2-(2-iodoethoxy)-1-iodobutane | 203250-05-9

• 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: (S)-4-(triphenylmethoxy)-2-(2-iodoethoxy)-1-iodobutane
• 英文别名: [[(2S)-4-iodo-2-(2-iodoethoxy)butoxy]-diphenylmethyl]benzene
• CAS: 203250-05-9
• 化学式: C₂₅H₂₆I₂O₂
• 分子量: 612.289
• InChiKey: LFSILUNCRISNRB-DEOSSOPVSA-N

物化性质

• 沸点：
  557.8±50.0 °C(Predicted)
• 密度：
  1.600±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-4-(triphenylmethoxy)-2-(2-iodoethoxy)-1-iodobutane 在 三甲基氯硅烷 、 caesium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Macrocyclic Bisindolylmaleimides:  Synthesis by Inter- and Intramolecular Alkylation

  摘要：

  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%.

  DOI：

  10.1021/jo971980h
• 作为产物：
  描述：

  (R)-3-chloro-1-O-trityl-1,2-propanediol 在 氢氧化钾 、 sodium hydroxide 、 sodium tetrahydroborate 、 copper(l) iodide 、 sudan red 、 potassium tert-butylate 、 四丁基碘化铵 、 臭氧 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 16.17h， 生成 (S)-4-(triphenylmethoxy)-2-(2-iodoethoxy)-1-iodobutane
  参考文献：
  名称：

  Macrocyclic Bisindolylmaleimides:  Synthesis by Inter- and Intramolecular Alkylation

  摘要：

  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%.

  DOI：

  10.1021/jo971980h

文献信息

• 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%.