(S)-2-((S)-4-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyrylamino)-3-methyl-butyric acid tert-butyl ester | 161878-63-3

• 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)-2-((S)-4-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyrylamino)-3-methyl-butyric acid tert-butyl ester
• 英文别名: Cbz-gGlu(OtBu)-Val-OtBu；tert-butyl (2S)-5-[[(2S)-3-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]amino]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoate
• CAS: 161878-63-3
• 化学式: C₂₆H₄₀N₂O₇
• 分子量: 492.613
• InChiKey: BQEFTVWMYQNFAH-FPOVZHCZSA-N

物化性质

• 沸点：
  632.1±55.0 °C(predicted)
• 密度：
  1.105±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-((S)-4-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyrylamino)-3-methyl-butyric acid tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (S)-2-((S)-4-Amino-4-tert-butoxycarbonyl-butyrylamino)-3-methyl-butyric acid tert-butyl ester
  参考文献：
  名称：

  The Synthesis and Thymidylate Synthase Inhibitory Activity of L-.gamma.-L-Linked Dipeptide and L-.gamma.-Amide Analogs of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)

  摘要：

  Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.

  DOI：

  10.1021/jm00046a014
• 作为产物：
  描述：

  L-缬氨酸叔丁酯盐酸盐 、 Z-谷安酸叔丁基酯 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙腈 为溶剂， 以98 %的产率得到(S)-2-((S)-4-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyrylamino)-3-methyl-butyric acid tert-butyl ester
  参考文献：
  名称：

  [EN] METHOD FOR PREVENTING INSECT DAMAGE TO PLANTS
  [FR] PROCÉDÉ DE LUTTE CONTRE LES DOMMAGES CAUSÉS PAR LES INSECTES SUR LES VÉGÉTAUX
  [JA] 植物の虫害を防止する方法

  摘要：

  植物の虫害を防止する技術等の農園芸分野における有用な技術を提供する。各種グルタミン酸誘導体を利用することにより植物の虫害を防止する。

  公开号：

  WO2024010005A1

文献信息

• An economical approach for peptide synthesis<i>via</i>regioselective C–N bond cleavage of lactams
  作者：Wataru Muramatsu、Hisashi Yamamoto

  DOI：10.1039/d2sc01466a

  日期：——

  An economical, solvent-free, and metal-free method for peptide synthesis via C–N bond cleavage using lactams has been developed. The method not only eliminates the need for condensation agents and their auxiliaries, which are essential for conventional peptide synthesis, but also exhibits high atom economy. The reaction is versatile because it can tolerate side chains bearing a range of functional

  已经开发出一种经济、无溶剂和无金属的肽合成方法，该方法通过使用内酰胺的 C-N 键裂解来合成肽。该方法不仅不需要缩合剂及其助剂，而缩合剂及其助剂是常规肽合成所必需的，而且还具有很高的原子经济性。该反应是通用的，因为它可以耐受带有一系列官能团的侧链，在没有外消旋或聚合的情况下提供高达 >99% 的相应肽产率。此外，开发的策略能够实现肽段偶联，提供对作为蜘蛛丝蛋白中重复序列出现的六肽的访问。
• [EN] METHOD FOR PREVENTING INSECT DAMAGE TO PLANTS<br/>[FR] PROCÉDÉ DE LUTTE CONTRE LES DOMMAGES CAUSÉS PAR LES INSECTES SUR LES VÉGÉTAUX<br/>[JA] 植物の虫害を防止する方法
  申请人：[en]AJINOMOTO CO., INC.;[ja]味の素株式会社

  公开号：WO2024010005A1

  公开（公告）日：2024-01-11

  植物の虫害を防止する技術等の農園芸分野における有用な技術を提供する。各種グルタミン酸誘導体を利用することにより植物の虫害を防止する。
• The Synthesis and Thymidylate Synthase Inhibitory Activity of L-.gamma.-L-Linked Dipeptide and L-.gamma.-Amide Analogs of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)
  作者：Graham M. F. Bisset、Vassilios Bavetsias、Timothy J. Thornton、Krzysztof Pawelczak、A. Hilary Calvert、Leslie R. Hughes、Ann L. Jackman

  DOI：10.1021/jm00046a014

  日期：1994.9

  Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.