methyl methyl-L-leucinate hydrochloride | 3339-45-5

• 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: methyl methyl-L-leucinate hydrochloride
• 英文别名: (S)-Methyl 4-methyl-2-(methylamino)pentanoate hydrochloride；methyl (2S)-4-methyl-2-(methylamino)pentanoate;hydrochloride
• CAS: 3339-45-5
• 化学式: C₈H₁₇NO₂*ClH
• mdl: MFCD27578409
• 分子量: 195.689
• InChiKey: VKYPGIMVFQAVJF-FJXQXJEOSA-N

物化性质

• 熔点：
  127-128 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.25
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.875
• 拓扑面积：
  42.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  methyl methyl-L-leucinate hydrochloride 在 2,6-二甲基吡啶 、 盐酸 、 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of Aza HUN-7293

  摘要：

  The aza analogue of the cyclic heptadepsipeptide HUN-7293 (1), which is a potent naturally occurring inhibitor of inducible cell adhesion molecule expression, and its C-2(3) (MLEU3 C-2) epimer were prepared via solution-phase synthesis. Biological evaluations of these two compounds as inhibitors of cell adhesion molecules expression are detailed. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00336-x
• 作为产物：
  描述：

  (4S)-3-(chloromethyl)-4-(2-methylpropyl)-2,2-bis(trifluoromethyl)-1,3-oxazolidin-5-one 在 盐酸 、 三乙基硅烷 、 三氟乙酸 作用下， 反应 0.5h， 生成 methyl methyl-L-leucinate hydrochloride
  参考文献：
  名称：

  An Efficient Synthesis of N-Methylamino Acids and Some of Their Derivatives

  摘要：

  通过N-氯甲基化和三乙基硅烷/三氟乙酸处理，从六氟丙酮保护的氨基酸出发，通过立体选择性的一锅法步骤，可以高产率地获得N-甲基氨基酸衍生物。

  DOI：

  10.1055/s-1998-1998

文献信息

• Synthesis and Biological Activity of Peptides Related to Eledoisin. II. Hexapeptide Amides Containing<i>N</i>-Methylamino Acids
  作者：Hiroshi Sugano、Ko Higaki、Muneji Miyoshi

  DOI：10.1246/bcsj.46.231

  日期：1973.1

  Eledoisin-like hexapeptides were synthesized in order to obtain longer-lasting hypotensive analogs. A part of the amino acid of the standard pep tide, H–Lys–Phe–Ile–Gly–Leu–Met–NH2 (1), was replaced by N-methylamino acid. It was found, in these syntheses, that when the C-terminal amino acid of a carboxy component was an N-methylamino acid, a system of dicyclohexylcarbodiimide plus 1-hydroxybenzotriazole was a useful coupling agent. With regard to the hypotensive effect in rabbits, H–Lys–Phe–Melle–Gly–Leu–Met–NH2 (2) and H–Lys–Phe–Ile–Gly–Melle–Met–NH2 (6) show much less activity; H–Lys–MePhe–Ile–Gly–Leu–Met–NH2 (3) and H–Lys–MePhe–Ile–Gly–MeLeu–Met–NH2 (7) show a substantial activity, though weaker than the standard one. On the other hand, H–Lys–Phe–Ile–Gly–MeLeu–Met–NH2 (5) and H–Lys–Phe–Ile–Sar–Leu–Met–NH2(4) show a higher activity than 1. These results indicate that, in some cases, the replacement of an amide bond by an N-methylamide bond without any change in the side chain of amino acid would have an important influence on the activity. The duration of the action of N-methypeptildes synthesized was unexpectedly of the same order of magnitude as that of 1.

  为获得更持久降压效果的模拟物，合成了促咽激素样六肽。将标准肽H-Lys-Phe-Ile-Gly-Leu-Met-NH2（1）中的部分氨基酸替换为N-甲基氨基酸。在这些合成中，发现当羧基部分C末端氨基酸为N-甲基氨基酸时，二环己基碳二亚胺加1-羟基苯并三唑是一种有用的偶联剂。关于对兔子的降压效果，H-Lys-Phe-Melle-Gly-Leu-Met-NH2（2）和H-Lys-Phe-Ile-Gly-Melle-Met-NH2（6）的活性大大降低；H-Lys-MePhe-Ile-Gly-Leu-Met-NH2（3）和H-Lys-MePhe-Ile-Gly-MeLeu-Met-NH2（7）显示出相当的活性，尽管弱于标准肽。另一方面，H-Lys-Phe-Ile-Gly-MeLeu-Met-NH2（5）和H-Lys-Phe-Ile-Sar-Leu-Met-NH2（4）的活性高于1。这些结果表明，在某些情况下，将酰胺键替换为N-甲基酰胺键而不改变氨基酸侧链会对活性产生重要影响。合成的N-甲基肽的作用持续时间与1相当。
• [EN] INHIBITORS OF NOROVIRUS AND CORONAVIRUS REPLICATION<br/>[FR] INHIBITEURS DE LA RÉPLICATION DE NOROVIRUS ET DE CORONAVIRUS
  申请人：COCRYSTAL PHARMA INC

  公开号：WO2021206876A1

  公开（公告）日：2021-10-14

  Compounds of Formula (I) and methods of inhibiting the replication of viruses in a biological sample or patient, of reducing the amount of viruses in a biological sample or patient, and of treating a virus infection in a patient, comprising administering to said biological sample or patient an effective amount of a compound represented by Formula (I), a compound of Table A or B or a pharmaceutically acceptable salt thereof.

  公式（I）化合物及抑制生物样本或患者中病毒复制、减少生物样本或患者中病毒数量、以及治疗患者病毒感染的方法，包括向所述生物样本或患者投与由公式（I）表示的化合物、表A或B中的化合物或其药用可接受盐的有效量。
• Brop: A new reagent for coupling N-methylated amino acids
  作者：Jacques Coste、Marie-Noëlle Dufour、Antoine Pantaloni、Bertrand Castro

  DOI：10.1016/s0040-4039(00)94598-2

  日期：1990.1

  BroP (bromo tris(dimethylamino) phosphonium hexafluorophosphate) is a particularly suitable reagent for coupling N-methylated amino acids. It is stable and gives very high yields in short reaction times. Dipeptides are obtained without appreciable epimerization.

  BroP（溴化三（二甲基氨基）六氟磷酸phospho）是用于偶联N-甲基化氨基酸的特别合适的试剂。它是稳定的，并且在短的反应时间内给出了很高的产率。在没有明显差向异构的情况下获得二肽。
• Synthesis and stereochemistry of JBIR-81, a peptide enamide derived from aspergilli
  作者：Ryo Katsuta、Mami Toyoda、Arata Yajima、Ken Ishigami、Tomoo Nukada

  DOI：10.1016/j.tetlet.2018.01.080

  日期：2018.3

  The absolute stereochemistry of an aspergilli-derived peptide enamide, JBIR-81, was determined to be 12S, 15S by the first synthesis of (12S,15S)-JBIR-81 and its epimer. The overall yield was 56% over six steps from N-methyl-l-leucine. The (Z)-enamide structure was effectively constructed with use of a copper (I) catalyzed coupling reaction between a vinyl halide and a carboxamide.

  的绝对立体化学的曲霉衍生肽烯酰胺，JBIR-81，被确定为12小号，15小号通过（12的第一合成小号，15小号）-JBIR-81和它的差向异构体。由N-甲基-1-亮氨酸经六个步骤的总产率为56％。通过使用铜（I）催化的乙烯基卤化物和羧酰胺之间的偶联反应，可以有效地构建（Z）-酰胺结构。
• [EN] CYCLIC PEPTIDE ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES PEPTIDIQUES CYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2019052545A1

  公开（公告）日：2019-03-21

  Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of lipoprotein signal peptidase II (LspA), a key protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

  本文提供了抗菌化合物，其中在某些实施例中，这些化合物具有广谱生物活性。在各种实施例中，这些化合物通过抑制脂蛋白信号肽酶II（LspA）来发挥作用，这是细菌中的关键蛋白质。还提供了使用所述化合物的药物组合物和治疗方法。