(2S)-2-(benzyloxycarbonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide | 95303-76-7

• 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: (2S)-2-(benzyloxycarbonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide
• 英文别名: Z-Val-Leu-ol；benzyl N-[(2S)-1-[[(2S)-1-hydroxy-4-methylpentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 95303-76-7
• 化学式: C₁₉H₃₀N₂O₄
• 分子量: 350.458
• InChiKey: WNTOWHFDYMAPDV-IRXDYDNUSA-N

物化性质

• 沸点：
  556.4±45.0 °C(Predicted)
• 密度：
  1.091±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  25.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  87.66
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S)-2-(benzyloxycarbonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide 在 palladium on activated charcoal pyridine-SO3 complex 、 氢气 、 4-甲基苯磺酸吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 94.5h， 生成 (2S)-N-((1S)-1-(2,5-dioxolanyl)-3-methylbutyl)-3-methyl-2-((3-pyridylmethyl)carbonylamino)butanamide
  参考文献：
  名称：

  Exploration of cornea permeable calpain inhibitors as anticataract agents

  摘要：

  To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an alpha-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-in soluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hermacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00612-0
• 作为产物：
  描述：

  Z-Val-Leu-OMe 在 sodium tetrahydroborate 作用下， 以80%的产率得到(2S)-2-(benzyloxycarbonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide
  参考文献：
  名称：

  氨基酸和多肽。十一。埃及伊蚊和德国小Bl的引诱剂和驱避剂肽的合成。

  摘要：

  Z-Gly-Val-Ser-Phe-Val-Leu-OMe 及相关肽通过传统的溶液法合成，并对其对埃及伊蚊（Aedes aegypti）和德国小蠊（Blattella germanica）的吸引和排斥活性进行了检验。Z-Val-Leu-OMe 对埃及伊蚊和德国小蠊均表现出强效的排斥活性。

  DOI：

  10.1248/cpb.32.4608

文献信息

• Amino acids and peptides. XI. Synthesis of attractant and repellent peptides for Aedes aegypti and Blattella germanica.
  作者：YOSHIO OKADA、SHIN IGUCHI、TAKAAKI HIRAI、YOSHITAKA GOTO、MASAMI YAGYU、HARUAKI YAJIMA

  DOI：10.1248/cpb.32.4608

  日期：——

  Z-Gly-Val-Ser-Phe-Val-Leu-OMe and related peptides were synthesized by the conventional solution method and their attractant and repellent activities for Aedes aegypti (mosquito) and Blattella germanica (cockroach) were examined. Z-Val-Leu-OMe exhibited potent repellent activity against not only Aedes aegypti but also Blattella germanica.

  Z-Gly-Val-Ser-Phe-Val-Leu-OMe 及相关肽通过传统的溶液法合成，并对其对埃及伊蚊（Aedes aegypti）和德国小蠊（Blattella germanica）的吸引和排斥活性进行了检验。Z-Val-Leu-OMe 对埃及伊蚊和德国小蠊均表现出强效的排斥活性。
• Exploration of cornea permeable calpain inhibitors as anticataract agents
  作者：Masayuki Nakamura、Masazumi Yamaguchi、Osamu Sakai、Jun Inoue

  DOI：10.1016/s0968-0896(02)00612-0

  日期：2003.4

  To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an alpha-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-in soluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hermacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model. (C) 2003 Elsevier Science Ltd. All rights reserved.