(1S,2R)-1-{[(2S,4S)-1-((S)-2-cyclopentyloxycarbonylamino-oct-7-enoyl)-4-hydroxypyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester | 769167-57-9

• 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: (1S,2R)-1-{[(2S,4S)-1-((S)-2-cyclopentyloxycarbonylamino-oct-7-enoyl)-4-hydroxypyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester
• 英文别名: methyl (1R,2S)-1-[[(2S,4S)-1-[(2S)-2-(cyclopentyloxycarbonylamino)non-8-enoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate
• CAS: 769167-57-9
• 化学式: C₂₇H₄₁N₃O₇
• 分子量: 519.638
• InChiKey: KLELNUHLUGOINU-ZFQKPUMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,2R)-1-{[(2S,4S)-1-((S)-2-cyclopentyloxycarbonylamino-oct-7-enoyl)-4-hydroxypyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 8.0h， 生成 (1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Efficient Large-Scale Synthesis of BILN 2061, a Potent HCV Protease Inhibitor, by a Convergent Approach Based on Ring-Closing Metathesis

  摘要：

  A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce > 400 kg of cyclized product.

  DOI：

  10.1021/jo060285j
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 1-甲基吡咯烷 、 硫酸 、 N,N-二异丙基乙胺 、 sodium 2-ethylhexanoic acid 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 10.5h， 生成 (1S,2R)-1-{[(2S,4S)-1-((S)-2-cyclopentyloxycarbonylamino-oct-7-enoyl)-4-hydroxypyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester
  参考文献：
  名称：

  Efficient Large-Scale Synthesis of BILN 2061, a Potent HCV Protease Inhibitor, by a Convergent Approach Based on Ring-Closing Metathesis

  摘要：

  A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce > 400 kg of cyclized product.

  DOI：

  10.1021/jo060285j

文献信息

• Olefin ring-closing metathesis as a powerful tool in drug discovery and development – potent macrocyclic inhibitors of the hepatitis C virus NS3 protease
  作者：Youla S. Tsantrizos、Jean-Marie Ferland、Andrew McClory、Martin Poirier、Vittorio Farina、Nathan K. Yee、Xiao-jun Wang、Nizar Haddad、Xudong Wei、Jinghua Xu、Li Zhang

  DOI：10.1016/j.jorganchem.2006.09.027

  日期：2006.12

  Peptidomimetic inhibitors of the hepatitis C NS3 protease often exhibit poor biopharmaceutical properties. Structure modification of a substrate-based tripeptide into a β-strand 15-membered ring scaffold provided a new class of peptidomimetics that are significantly superior as drug candidates to their acyclic precursors. Tripeptide dienes composed of three unnatural amino acid residues with numerous

  丙型肝炎病毒NS3蛋白酶的拟肽抑制剂通常表现出较差的生物药物特性。将基于底物的三肽结构修饰成β链15元环骨架，提供了一类新型的拟肽，它们作为药物的候选者显着优于其无环前体。使用闭环复分解（RCM），将具有三个手性中心的三个非天然氨基酸残基组成的三肽二烯有效地转化为高非对映异构体纯度的大环肽。对无环二烯的构象和RCM反应方案进行了广泛研究和优化，以实现潜在丙种肝炎感染治疗剂的有效合成。
• MACROCYCLIC PEPTIDES ACTIVE AGAINST THE HEPATITIS C VIRUS
  申请人：LLINAS-BRUNET Montse

  公开号：US20090264346A1

  公开（公告）日：2009-10-22

  Compounds of formula (I): wherein R 1 , R 2 , X, R 3 , D, and the dotted line b are as defined herein; or a pharmaceutically acceptable salt or ester thereof, are useful as inhibitors of the HCV NS3 protease.

  式(I)的化合物：其中R1，R2，X，R3，D和虚线b的定义如本文所述；或其药学上可接受的盐或酯，可用作HCV NS3蛋白酶的抑制剂。
• US7189844B2
  申请人：——

  公开号：US7189844B2

  公开（公告）日：2007-03-13
• US7268211B2
  申请人：——

  公开号：US7268211B2

  公开（公告）日：2007-09-11
• US7642235B2
  申请人：——

  公开号：US7642235B2

  公开（公告）日：2010-01-05