NH2-Pro-N-Cbz-Ser-phenacylester | 791778-43-3

• 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: NH2-Pro-N-Cbz-Ser-phenacylester
• 英文别名: [(2S)-3-oxo-3-phenacyloxy-2-(phenylmethoxycarbonylamino)propyl] (2S)-pyrrolidine-2-carboxylate
• CAS: 791778-43-3
• 化学式: C₂₄H₂₆N₂O₇
• 分子量: 454.48
• InChiKey: YFOOQBXFNZHJLE-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  NH2-Pro-N-Cbz-Ser-phenacylester 在 盐酸 、 五氟苯酚 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 氢气 、 1-羟基苯并三唑 、 O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， -20.0~20.0 ℃ 、101.33 kPa 条件下， 反应 135.0h， 生成
  参考文献：
  名称：

  Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated fromStreptomyces hawaiiensis

  摘要：

  The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.

  DOI：

  10.1021/np500158q

文献信息

• Diversity-oriented synthesis of cyclic acyldepsipeptides leads to the discovery of a potent antibacterial agent
  作者：Aaron M. Socha、Nicholas Y. Tan、Kerry L. LaPlante、Jason K. Sello

  DOI：10.1016/j.bmc.2010.08.032

  日期：2010.10.15

  structure, featuring the Joullié-Ugi three-component reaction, was developed. This multicomponent reaction and a related multicomponent reaction, the Ugi four-component reaction, were used to prepare analogs that were designed using the principles of conformational analysis. These cyclic acyldepsipeptides were tested for their activity against drug-resistant, clinical isolates of Staphylococci and Enterococci

  一类被称为Enepteptins的环状环肽肽抗生素最近因其对多种耐药性细菌的活性而引起了广泛关注，其中包括耐甲氧西林的金黄色葡萄球菌和耐万古霉素的粪肠球菌。这些抗生素通过其新颖的作用机制进一步区别于其中，它们结合并解除了对细胞质蛋白酶ClpP的严格控制的活性。尽管天然产物的药理学性能较差，但一种合成的衍生物，名为acyldepsipeptide 4（ADEP 4），在体外和小鼠细菌感染模型中均显示出显着的抗菌活性。开发了以Joullié-Ugi三组分反应为特征的ADEP 4肽内酯核心结构的新途径。该多组分反应和相关的多组分反应Ugi四组分反应被用来制备类似物，所述类似物是利用构象分析原理设计的。测试了这些环状酰基肽肽对抗药性，临床分离株的活性。葡萄球菌和肠球菌。一种用四甲基哌酸酯代替哌酸酯的ADEP 4类似物，其对肠球菌的体外抗菌活性比母体化合物高四倍。
• [EN] ENOPEPTINS, USES THEREOF, AND METHODS OF SYNTHESIS THERETO<br/>[FR] ENOPEPTINES, UTILISATIONS DE CELLES-CI, ET PROCÉDÉS DE SYNTHÈSE DE CELLES-CI
  申请人：UNIV BROWN

  公开号：WO2012135615A3

  公开（公告）日：2013-01-03
• US7405201B2
  申请人：——

  公开号：US7405201B2

  公开（公告）日：2008-07-29
• Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated from<i>Streptomyces hawaiiensis</i>
  作者：Jordan D. Goodreid、Keith Wong、Elisa Leung、Shannon E. McCaw、Scott D. Gray-Owen、Alan Lough、Walid A. Houry、Robert A. Batey

  DOI：10.1021/np500158q

  日期：2014.10.24

  The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.