[(S)-4-(4-tert-Butoxy-phenyl)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-butyrylamino]-acetic acid ethyl ester | 301544-43-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(S)-4-(4-tert-Butoxy-phenyl)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-butyrylamino]-acetic acid ethyl ester
• CAS: 301544-43-4
• 化学式: C₃₃H₃₈N₂O₇
• 分子量: 574.674
• InChiKey: MSGJBFPQTQYDOI-MBCWZBCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  42.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  123.19
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [(S)-4-(4-tert-Butoxy-phenyl)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-butyrylamino]-acetic acid ethyl ester 在 碳酸二异丙酯 、 1-羟基苯并三唑 、 二乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 ethyl ((3S)-4-(4-(tert-butoxy)phenyl)-2-hydroxy-3-(2-((R)-N-methyl-5-((E)-2-nitroguanidino)-2-((phenylmethyl)sulfonamido)pentanamido)acetamido)butanoyl)glycinate
  参考文献：
  名称：

  Novel, potent and selective chimeric FXa inhibitors featuring hydrophobic p1-ketoamide moieties

  摘要：

  Judicious combination of P-region sequences of highly potent anticoagulant proteins including NAPS, NAP6, Ecotin, and Antistasin with SAR from small molecule FXa inhibitors led to a series of chimeric inhibitors of formula 1a-j. We report herein the design, synthesis, and biological activity of this novel family of FXa inhibitors that express both high in vitro potency and superb selectivity against related serine proteases. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00458-3
• 作为产物：
  描述：

  9H-fluoren-9-ylmethyl [(1S)-1-(4-tert-butoxybenzyl)-2-hydroxyethyl]carbamate 在 吡啶 、 二氯乙酸 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.0h， 生成 [(S)-4-(4-tert-Butoxy-phenyl)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-butyrylamino]-acetic acid ethyl ester
  参考文献：
  名称：

  Novel, potent and selective chimeric FXa inhibitors featuring hydrophobic p1-ketoamide moieties

  摘要：

  Judicious combination of P-region sequences of highly potent anticoagulant proteins including NAPS, NAP6, Ecotin, and Antistasin with SAR from small molecule FXa inhibitors led to a series of chimeric inhibitors of formula 1a-j. We report herein the design, synthesis, and biological activity of this novel family of FXa inhibitors that express both high in vitro potency and superb selectivity against related serine proteases. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00458-3

文献信息

• New Synthetic Technology for Efficient Construction of α-Hydroxy-β-amino Amides via the Passerini Reaction¹
  作者：J. Edward Semple、Timothy D. Owens、Khanh Nguyen、Odile E. Levy

  DOI：10.1021/ol0061485

  日期：2000.9.1

  [reaction: see text] The Passerini reaction of N-protected amino aldehydes, isonitriles, and TFA using pyridine-type bases proceeds under mild conditions and directly affords alpha-hydroxy-beta-amino amide derivatives in moderate to high yields. These adducts are readily hydrolyzed to alpha-hydroxy-beta-amino carboxylic acids. Application of these key intermediates to concise syntheses of P(1)-alpha-ketoamide

  [反应：见正文]使用吡啶型碱的N-保护的氨基醛，异腈和TFA的Passerini反应在温和的条件下进行，并以中等至高收率直接提供α-羟基-β-氨基酰胺衍生物。这些加合物容易水解成α-羟基-β-氨基羧酸。说明了这些关键中间体在简明P（1）-α-酮酰胺蛋白酶抑制剂合成中的应用。