(S)-3-<4-<2-Carboxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>ethyl>phenoxy>-O-methyl-N--L-tyrosinyl>-L-tyrosine α-methyl ester | 118459-90-8

• 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)-3-<4-<2-Carboxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>ethyl>phenoxy>-O-methyl-N--L-tyrosinyl>-L-tyrosine α-methyl ester
• 英文别名: (S)-3-<4-<2-carboxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>ethyl>phenoxy>-O-methyl-N--L-tyrosyl>-L-tyrosine α-methyl ester；(S)-3-[4-(2-carboxy-2-{[(1,1-dimethylethoxy)carbonyl]amino}ethyl)phenoxy]-O-methyl-N-{O-methyl-N-[(phenylmethoxy)carbonyl]-L-tyrosyl}-L-tyrosine α-methyl ester；(2S)-3-[4-[2-methoxy-5-[(2S)-3-methoxy-2-[[(2S)-3-(4-methoxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]amino]-3-oxopropyl]phenoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 118459-90-8
• 化学式: C₄₃H₄₉N₃O₁₂
• 分子量: 799.875
• InChiKey: QONLEJNJDWIMBH-IMKBVMFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  58
• 可旋转键数：
  22
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  197
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-3-<4-<2-Carboxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>ethyl>phenoxy>-O-methyl-N--L-tyrosinyl>-L-tyrosine α-methyl ester 在 钯 N-甲基吗啉 、 氢气 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 24.0h， 生成 <9S-(9R*,12R*,15R*)>-methyl 15-<<(1,1-dimethylethoxy)carbonyl>amino>-4-methoxy-12-<(4-methoxyphenyl)methyl>-11,14-dioxo-2-oxa-10,13-diazatricyclo<15.2.2.1^3,7>docosa-3,5,7(22),17,19,20-hexaene-9-carboxylate
  参考文献：
  名称：

  异二酪氨酸衍生环状三肽 OF4949-III 和 K-13 的全合成。确定 K-13 的绝对构型

  摘要：

  两个环状三肽OF4949-111和K-13的不对称合成已经完成。前者化合物的绝对立体化学归属已得到确认，后者的绝对构型首次建立。完全分化的异二酪氨酸的方便双向合成，一种常见的

  DOI：

  10.1021/ja00185a042
• 作为产物：
  描述：

  对氯肉桂酸 在 palladium on activated charcoal 吡啶 、 盐酸 、 lithium hydroxide 、 正丁基锂 、 samarium diiodide 、 2,4,6-三异丙基苯磺酰叠氮化物 、 氢气 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 丙酮 为溶剂， -78.0~35.0 ℃ 、101.33 kPa 条件下， 反应 42.03h， 生成 (S)-3-<4-<2-Carboxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>ethyl>phenoxy>-O-methyl-N--L-tyrosinyl>-L-tyrosine α-methyl ester
  参考文献：
  名称：

  A Formal Total Synthesis of the ACE Inhibitor K-13. An Application of Arene-Ruthenium Chemistry to Complex Chemical Synthesis

  摘要：

  Stoichiometric ruthenium activation of 4-chlorophenylalanine derivatives toward nucleophilic substitution, using phenoxide nucleophiles that are derived from protected dipeptides, allowed the formation of isodityrosine derivatives that are synthetic precursors to the ACE inhibitor K-13. An evaluation of carboxyl blocking groups revealed that a 2-bromoethyl ester is the most useful in terms of its compatibility with ruthenium complexation and subsequent nucleophile addition but that its removal is problematic. Conversion to iodoethyl ester using Finkelstein reaction conditions, in the presence of the peptide and amino acid functionality, provided a solution to this problem, since the iodoethyl group was easily removed on treatment with samarium diiodide.

  DOI：

  10.1021/jo00088a009

文献信息

• The total syntheses of the isodityrosine-derived cyclic tripeptides OF4949-III and K-13. Determination of the absolute configuration of K-13
  作者：David A. Evans、Jonathan A. Ellman

  DOI：10.1021/ja00185a042

  日期：1989.2

  The asymmetric syntheses of the two cyclic tripeptides OF4949-111 and K-13 have been completed. The absolute stereochemical assignment of the former compound has been confirmed, while the absolute configuration of the latter has been established for the first time. The expedient bidirectional synthesis of a fully differentiated isodityrosine, a common

  两个环状三肽OF4949-111和K-13的不对称合成已经完成。前者化合物的绝对立体化学归属已得到确认，后者的绝对构型首次建立。完全分化的异二酪氨酸的方便双向合成，一种常见的
• A Formal Total Synthesis of the ACE Inhibitor K-13. An Application of Arene-Ruthenium Chemistry to Complex Chemical Synthesis
  作者：Anthony J. Pearson、Kieseung Lee

  DOI：10.1021/jo00088a009

  日期：1994.5

  Stoichiometric ruthenium activation of 4-chlorophenylalanine derivatives toward nucleophilic substitution, using phenoxide nucleophiles that are derived from protected dipeptides, allowed the formation of isodityrosine derivatives that are synthetic precursors to the ACE inhibitor K-13. An evaluation of carboxyl blocking groups revealed that a 2-bromoethyl ester is the most useful in terms of its compatibility with ruthenium complexation and subsequent nucleophile addition but that its removal is problematic. Conversion to iodoethyl ester using Finkelstein reaction conditions, in the presence of the peptide and amino acid functionality, provided a solution to this problem, since the iodoethyl group was easily removed on treatment with samarium diiodide.