N-Cbz-L-丙氨酰-L-丙氨酸琥珀酰亚胺酯 | 16946-96-6

• 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
• 中文名称: N-Cbz-L-丙氨酰-L-丙氨酸琥珀酰亚胺酯
• 英文名称: N-Cbz-L-alanyl-L-alanine succinimido ester
• 英文别名: N-CBZ-L-Ala-N-L-Ala-N-hydroxysuccinimide；Cbz-L-Ala-L-Ala-OSu；ZAlaAlaONSu；Z-Ala-Ala-N-hydroxysuccinimid；Z-Ala-Ala-ONSu；Z-Ala-Ala-OSu；(2,5-dioxopyrrolidin-1-yl) (2S)-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoate
• CAS: 16946-96-6
• 化学式: C₁₈H₂₁N₃O₇
• 分子量: 391.381
• InChiKey: ACLMYNMPYLHBIK-RYUDHWBXSA-N

物化性质

• 熔点：
  138-140 °C
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-Cbz-L-丙氨酰-L-丙氨酸琥珀酰亚胺酯 在 palladium on activated charcoal 碳酸氢钠 、 环己烯 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 2.5h， 生成 L-alanyl-L-alanyl-DL-aminopimelic acid
  参考文献：
  名称：

  Peptides of 2-aminopimelic acid: antibacterial agents that inhibit diaminopimelic acid biosynthesis

  摘要：

  Succinyl-CoA:tetrahydrodipicolinate-N-succinyltransferase is a key enzyme in the biosynthesis of diaminopimelic acid (DAP), a component of the cell wall peptidoglycan of nearly all bacteria. This enzyme converts the cyclic precursor tetrahydrodipicolinic acid (THDPA) to a succinylated acyclic product. L-2-Aminopimelic acid (L-1), an acyclic analogue of THDPA, was found to be a good substrate for this enzyme and was shown to cause a buildup of THDPA in a cell-free enzyme system but was devoid of antibacterial activity. Incorporation of 1 into a di- or tripeptide yielded derivatives that exhibited antibacterial activity against a range of Gram-negative organisms. Of the five peptide derivatives tested, (L-2-aminopimelyl)-L-alanine (6) was the most potent. These peptides were shown to inhibit DAP production in intact resting cells. High levels (30 mM) of 2-aminopimelic acid were achieved in the cytoplasm of bacteria as a result of efficient uptake of the peptide derivatives through specific peptide transport systems followed, presumably, by cleavage by intracellular peptidases. Finally, the antibacterial activity of these peptides could be reversed by DAP or a DAP-containing peptide. These results demonstrate that the peptides containing L-2-aminopimelic acid exert their antibacterial action by inhibition of diaminopimelic acid biosynthesis.

  DOI：

  10.1021/jm00151a015
• 作为产物：
  描述：

  N,N'-二琥珀酰亚胺基碳酸酯 、 N-(苄氧羰基)-L-丙氨酰-L-丙氨酸 在 吡啶 作用下， 以 乙腈 为溶剂， 以79%的产率得到N-Cbz-L-丙氨酰-L-丙氨酸琥珀酰亚胺酯
  参考文献：
  名称：

  Peptides of 2-aminopimelic acid: antibacterial agents that inhibit diaminopimelic acid biosynthesis

  摘要：

  Succinyl-CoA:tetrahydrodipicolinate-N-succinyltransferase is a key enzyme in the biosynthesis of diaminopimelic acid (DAP), a component of the cell wall peptidoglycan of nearly all bacteria. This enzyme converts the cyclic precursor tetrahydrodipicolinic acid (THDPA) to a succinylated acyclic product. L-2-Aminopimelic acid (L-1), an acyclic analogue of THDPA, was found to be a good substrate for this enzyme and was shown to cause a buildup of THDPA in a cell-free enzyme system but was devoid of antibacterial activity. Incorporation of 1 into a di- or tripeptide yielded derivatives that exhibited antibacterial activity against a range of Gram-negative organisms. Of the five peptide derivatives tested, (L-2-aminopimelyl)-L-alanine (6) was the most potent. These peptides were shown to inhibit DAP production in intact resting cells. High levels (30 mM) of 2-aminopimelic acid were achieved in the cytoplasm of bacteria as a result of efficient uptake of the peptide derivatives through specific peptide transport systems followed, presumably, by cleavage by intracellular peptidases. Finally, the antibacterial activity of these peptides could be reversed by DAP or a DAP-containing peptide. These results demonstrate that the peptides containing L-2-aminopimelic acid exert their antibacterial action by inhibition of diaminopimelic acid biosynthesis.

  DOI：

  10.1021/jm00151a015

文献信息

• 7-Azetidinylquinolones as Antibacterial Agents. 3. Synthesis, Properties and Structure-Activity Relationships of the Stereoisomers Containing a 7-(3-Amino-2-methyl-1-azetidinyl) Moiety
  作者：Jordi Frigola、David Vano、Antoni Torrens、Angels Gomez-Gomar、Edmundo Ortega、Santiago Garcia-Granda

  DOI：10.1021/jm00007a017

  日期：1995.3

  de]-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents. A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior. The absolute configuration of the new azetidinylquinolones

  一系列立体化学纯的7-（3-氨基-2-甲基-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸制备了位于1、5和8位的取代基，以确定手性相对于外消旋混合物的效价和体内功效的影响（第2部分，参见：J. Med.Chem。1994，37， 4195-4210）。一系列手性9-氟-2,3-二氢-3-甲基-7-氧-10-（取代的1-氮杂环丁烷基）-7H-吡啶[1,2,3-de] -1,4-苯并恶嗪合成-6-羧酸以研究氮杂环丁烷部分对三环喹诺酮抗菌剂的作用。制备了一系列手性萘啶24a和24b以及喹诺酮33a（cetefloxacin）的氨基酸前药，并评估了其抗菌活性，溶解度和药代动力学行为。通过对拆分的氮杂环丁醇（15）和化合物25a（E-4767）的一种非对映异构盐进行X射线分析，可以确定新的氮杂环丁烷基喹诺酮类化合物的绝对构型，该化合物在体外和体内的总体情况最佳。
• Design and synthesis of peptide derivatives of a 3-deoxy-D-manno-2-octulosonic acid (KDO) analog as novel antibacterial agents acting upon lipopolysaccharide biosynthesis
  作者：Alf Claesson、Anita M. Jansson、Brian G. Pring、Stephen M. Hammond、Bertil Ekstroem

  DOI：10.1021/jm00395a022

  日期：1987.12

  cytidylyltransferase, attempts were made to design derivatives that would act as antibacterials against Gram-negative bacteria by inhibiting lipopolysaccharide biosynthesis. Compound 3 and the derivatives 15 and 16 containing an additional amino acid were not lethal to bacteria. However, compounds 17-22, which contain a N-terminally linked dipeptide, exhibited good antibacterial activity in vitro on testing against

  基于以下认识，氨基酸3（8-氨基-2,6-脱水-3,8-二脱氧-D-甘油-D-talo-辛酸）是有效的3-脱氧-甘露聚糖-抑制剂试图通过设计八辛酸胞苷基转移酶来设计衍生物，该衍生物通过抑制脂多糖的生物合成来作为革兰氏阴性菌的抗菌剂。化合物3以及含有额外氨基酸的衍生物15和16对细菌没有致死性。但是，含有N末端连接的二肽的化合物17-22在体外测试对革兰氏阴性细菌大肠杆菌和鼠伤寒沙门氏菌的菌株时表现出良好的抗菌活性。它们对革兰氏阳性细菌如金黄色葡萄球菌没有活性。
• Irreversible cysteine protease inhibitors of legumain
  申请人：Niestroj Andre

  公开号：US20060178315A1

  公开（公告）日：2006-08-10

  Presented are compounds represented by the following general formulas (I) and (II), for inhibiting cysteine protease legumain for modulating associated disease states in subjects.

  以下是由以下通用公式（I）和（II）代表的化合物，用于抑制半胱氨酸蛋白酶蛋白酶，以调节受试者中相关疾病状态。
• Neue Diphosphonsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0197478A1

  公开（公告）日：1986-10-15

  Diphosphonsaeure-Derivate der allgemeinen Formel I in der R1, R2, R3, R4 und R5 jeweils unabhaengig voneinander oder auch gemeinsam Wasserstoff oder neideres Alkyl bedeuten, wobei R, und X bzw. R3 und Y bzw. R4 und Z zusammen mit dem Stickstoffatom, an das sie gebunden sind, einen Fuenf-oder Sechsring bilden koennen, X und Y jeweils unabhaengig voneinander eine geradkettige oder verzweigte Alkylenkette mit 1-6 Kohlenstoffatomen, die gegebenfalls durch Aromaten oder Heteroaromaten substituiert sien kann, Z eine geradkettige oder verzweigte Alkylenkette mit 1-6 Kohlenstoffatomen, die durch Heteroatome unterbrochen und gegebenenfalls auch durch Aromaten oder Aromaten oder Heteroaromaten substituiert sien kann, n = 0-2 und A = Wasserstoff oder Hydroxy bedeuten, sowie deren pharmakologisch unbedenkliche Salze, Verfahren zu ihrer Herstellung sowie Arzneimittel, die diese Verbindungen enthalten zur Behandlung von Calciumstoffwechselstoerungen.

  通式 I 的二膦酸衍生物 其中 R1、R2、R3、R4 和 R5 各自独立或共同为氢或低级烷基，其中 R 和 X 或 R3 和 Y 或X和Y各自独立地代表具有 1-6 个碳原子的直链或支链亚烷基链，可任选被芳香族化合物或杂芳香族化合物取代，Z代表具有 1-6 个碳原子的直链或支链亚烷基链、n＝0-2，A＝氢或羟基，以及其药理学上可接受的盐、制备工艺和含有这些化合物的用于治疗钙代谢紊乱的药物。
• Synthesis of N-hydroxysuccinimide esters of N-protected amino acids and peptides using N,N?-disuccinimidyl sulfite
  作者：A. V. Il'ina、Yu. A. Davidovich、S. V. Rogozhin

  DOI：10.1007/bf01141728

  日期：1984.5