Cbz-D-isoGln-OH | 19522-39-5

• 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: Cbz-D-isoGln-OH
• 英文别名: Cbz-D-iGln；(R)-5-amino-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acid；D-4-(Carboxyamino)-glutaramic Acid 4-Benzyl Ester；(4R)-5-amino-5-oxo-4-(phenylmethoxycarbonylamino)pentanoic acid
• CAS: 19522-39-5
• 化学式: C₁₃H₁₆N₂O₅
• 分子量: 280.28
• InChiKey: NHFBOIIKTDKSRE-SNVBAGLBSA-N

物化性质

• 熔点：
  163-165°C
• 溶解度：
  甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Cbz-D-isoGln-OH 在 palladium 10% on activated carbon 、 氢气 、 盐酸 作用下， 以 甲醇 、 溶剂黄146 、 水 为溶剂， 反应 12.0h， 以62%的产率得到(R)-1-Amino-4-carboxy-1-oxobutan-2-aminium chloride
  参考文献：
  名称：

  Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

  摘要：

  Porphyromonas gingivalis (P.g.)-induced TNF-alpha can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 mu g/mL of MDP (MDP-low) up-regulated TNF-alpha by 29%, while 100 mu g/mL or higher (MDP-high) significantly decreased it (16% to 38%). MDP-high was found to affect the ubiquitin-editing enzyme A20 and activator protein 1 (AP1). An AP1 binding site was found in the promoter region of A20. A20 promoter activity was up-regulated after transfection of AP1 cDNA in cells. Four analogues of MDP (3-6) were prepared through a convergent strategy involving the synthesis of two unique carbohydrate fragments, 7a and 7b, using the peptide coupling reagents, EDCI and HOAt. Analogue 4 improved MDP function and P.g.-induced activities. We propose a new signaling pathway for TNF-alpha induction activated after exposing macrophages to both P.g. and MDP-high or analogue 4.

  DOI：

  10.1021/acs.jmedchem.6b00681
• 作为产物：
  描述：

  D-谷氨酸 在 氨 、 碳酸氢钠 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 85.25h， 生成 Cbz-D-isoGln-OH
  参考文献：
  名称：

  Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

  摘要：

  Porphyromonas gingivalis (P.g.)-induced TNF-alpha can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 mu g/mL of MDP (MDP-low) up-regulated TNF-alpha by 29%, while 100 mu g/mL or higher (MDP-high) significantly decreased it (16% to 38%). MDP-high was found to affect the ubiquitin-editing enzyme A20 and activator protein 1 (AP1). An AP1 binding site was found in the promoter region of A20. A20 promoter activity was up-regulated after transfection of AP1 cDNA in cells. Four analogues of MDP (3-6) were prepared through a convergent strategy involving the synthesis of two unique carbohydrate fragments, 7a and 7b, using the peptide coupling reagents, EDCI and HOAt. Analogue 4 improved MDP function and P.g.-induced activities. We propose a new signaling pathway for TNF-alpha induction activated after exposing macrophages to both P.g. and MDP-high or analogue 4.

  DOI：

  10.1021/acs.jmedchem.6b00681

文献信息

• Synthesis and reactions of O-acetylated benzyl α-glycosides of 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-N-acetylmuramoyl-l-alanyl-d-isoglutamine esters: the base-catalysed isoglutamine ⇄ glutamine rearrangement in peptidoglycan-related structures
  作者：Dina Keglević、Andrew E. Derome

  DOI：10.1016/0008-6215(89)84005-4

  日期：1989.2

  Abstract Condensation of benzyl 2-acetamido-6- O -(2-acetamido-3,4,6-tri- O -acetyl-2-deoxy-3- O -[( R -1-carboxyethyl]-α- d -glucopyranoside ( 2 ) and its 4-acetate ( 4 ) with l -alanyl- d -isoglutamine benzyl ester via the mixed anhydride method yielded N -[2- O -[benzyl 2-acetamido-6- O -(2-acetamido-3,4,6-tri- O -acetyl-2-deoxy-β- d -glucopyranosyl)-2,3-dideoxy-α- d -glucopyranosid-3-yl]-( R )-

  5和6的O脱乙酰基化导致异谷氨酰胺残基的酯交换和α→γ酰胺化，得到N-[2- O-[苄基2-乙酰氨基-6- O-（2-乙酰氨基-2-脱氧-β- d-吡喃葡萄糖基）-2，3-二脱氧-α-d-吡喃葡萄糖苷-3-基]-（R）-乳酰基] -1-丙氨酰基-d-异谷氨酰胺甲酯（8）和​​-谷氨酰胺甲酯（9）。用MgO-甲醇处理6，在GlcNAc残基处引起脱乙酰基作用，得到N-[2- O-[苄基2-乙酰氨基-6-O-（2-乙酰氨基-2-脱氧-β-d-葡萄糖吡喃糖基）的混合物-4- O-乙酰基-2,3-二脱氧-α-d-吡喃葡萄糖苷-3-基]-（R）-乳酰基] -1-丙氨酰-d-异谷氨酰胺甲酯（11）和-谷氨酰胺甲酯（12 ）。肽聚糖相关结构的苄基或甲基酯保护与任何需要碱性介质的反应都不兼容。
• The First Total Synthesis of Lipid II:  The Final Monomeric Intermediate in Bacterial Cell Wall Biosynthesis
  作者：Michael S. VanNieuwenhze、Scott C. Mauldin、Mohammad Zia-Ebrahimi、Brian E. Winger、William J. Hornback、Shankar L. Saha、James A. Aikins、Larry C. Blaszczak

  DOI：10.1021/ja017386d

  日期：2002.4.1

  Bacterial peptidoglycan is composed of a network of beta-[1,4]-linked glyan strands that are cross-linked through pendant peptide chains. The final product, the murein sacculus, is a single, covalently closed macromolecule that precisely defines the size and shape of the bacterial cell. The recent increase in bacterial resistance to cell wall active agents has led to a resurgence of activity directed

  细菌肽聚糖由通过悬垂肽链交联的β-[1,4]-连接的聚糖链网络组成。最终产物，胞壁质球囊，是一个单一的、共价闭合的大分子，它精确地定义了细菌细胞的大小和形状。最近细菌对细胞壁活性剂耐药性的增加导致了旨在提高我们对分子水平耐药机制理解的活动的复苏。生物合成酶及其天然底物可以成为这一努力的宝贵工具。虽然现代实验技术已经导致肽聚糖生物合成中使用的生物合成酶的分离和纯化，但从天然底物中确保其必需底物的有用数量仍然存在问题。
• Synthesis of Fluoro-containing muramyl dipeptide analogs
  作者：Zheng-Fu Wang、Jie-Cheng Xu

  DOI：10.1016/s0040-4020(98)00738-8

  日期：1998.10

  Twelve Fluoro-containing muramyl dipeptide analogs with perfluoroalkyl at C1 of sugar moiety or C-terminal of peptidyl chain were synthesized.

  合成了十二个在糖基的C1或肽基链的C端具有全氟烷基的含氟的对甲基二肽类似物。
• Preparation of<i>N</i>-Acetylmuramyl-L-[U-¹⁴<i>C</i>]alanyl-D-isoglutamine<i>via</i>a Novel Synthetic Route
  作者：Shoichi Kusumoto、Kazuhiro Ikenaka、Tetsuo Shiba

  DOI：10.1246/bcsj.52.1177

  日期：1979.4

  anyl-D-isoglutamine, its labeled compound, i.e., N-acetylmuramyl-L-[U-14C]alanyl-D-isoglutamine was synthesized. For this purpose, an entirely novel synthetic route for the muramyl dipeptide was exploited using cold materials and applied to the preparation of the labeled compound. A convenient synthetic procedure of isoglutamine derivatives is also described.

  为研究免疫佐剂活性N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺的作用机制，合成了其标记化合物N-乙酰胞壁酰-L-[U-14C]丙氨酰-D-异谷氨酰胺。为此，使用冷材料开发了一种全新的胞壁酰二肽合成路线，并将其应用于标记化合物的制备。还描述了异谷氨酰胺衍生物的方便合成程序。
• [EN] ANTI-CANCER COMPOUNDS CONTAINING CYCLOPENTAQUINAZOLINE RING<br/>[FR] COMPOSES ANTI-CANCER CONTENANT UN NOYAU DE CYCLOPENTAQUINAZOLINE
  申请人：BRITISH TECHNOLOGY GROUP LIMITED

  公开号：WO1995030673A1

  公开（公告）日：1995-11-16

  (EN) Cyclopentaquinazoline of formula (I), wherein R1 is hydrogen, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxyalkyl or C1-4 fluoroalkyl; wherein R2 is hydrogen, C1-4 alkyl, C3-4 alkenyl, C3-4 alkynyl, C2-4 hydroxyalkyl, C2-4 halogenoalkyl or C1-4 cyanoalkyl; Ar1 is phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which may optionally bear one or two substituents selected from halogeno, hydroxy, amino, nitro, cyano, trifluoromethyl, C1-4 alkyl and C1-4 alkoxy; and wherein R3 is a group of the formula: -A1-Ar2-A2-Y1, in which A1 is a bond between the $g(a)-carbon atom of the group -CONHCH(CO2H)- and Ar2 or is a C1-2 alkylene group; Ar2 is phenylene, tetrazoldiyl, tiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which in the case of phenylene may optionally bear one or two substituents on the ring selected from halogeno, nitro, C1-4 alkyl and C1-4 alkoxy; A2 is a C1-3 alkylene or C2-3 alkenylene group; and a pharmaceutically acceptable salt or ester thereof are of therapeutic value particularly in the treatment of cancer.(FR) Cyclopentaquinazoline représenté par la formule (I), dans laquelle R1 représente hydrogène, amino, alkyle C1-4, alcoxy C1-4 , hydroxyalkyle C1-4 ou fluoroalkyle C1-4; dans laquelle R2 représente hydrogène, alkyle C1-4, alcényle C3-4, alcynyle C3-4, hydroxyalkyle C2-4, alogénoalkyle C2-4 ou cyanoalkyle C1-4; Ar1 représente phenylène, thiophénediyle, thiazolediyle, pyridinediyle ou pyrimidinediyle pouvant éventuellement porter un ou deux substituants sélectionés à partir de halogéno, hydroxy, amino, nitro, cyano, trifluorométhyle, alkyle C1-4 et alcoxy C1-4; et dans laquelle R3 représente un groupe de formule: -A1-Ar2-A2-Y1, dans laquelle A1 représente une liaison entre l'atome de $g(a)-carbone du groupe -CONHCH(CO2H) et un groupe alkylène C1-2; Ar2 représente phénylène, tétrazoldiyle, tiophénediyle, thiazolediyle, pyridinediyle ou pyrimidinediyle qui, dans le cas de phénylène, peut éventuellement porter un ou deux substituants sur le noyau sélectionnés à partir de halogéno, nitro, alkyle C1-4 et alcoxy C1-4; A2 représente un groupe alkylène C1-3 ou alkénylène C2-3; ainsi qu'un de ses sels ou de ses esters présentant une valeur thérapeutique, en particulier, dans le traitement du cancer.

  (I)式中的环戊喹唑啉，其中R1为氢、氨基、C1-4烷基、C1-4烷氧基、C1-4羟基烷基或C1-4氟代烷基；R2为氢、C1-4烷基、C3-4烯基、C3-4炔基、C2-4羟基烷基、C2-4卤代烷基或C1-4氰基烷基；Ar1为苯基、噻吩二基、噻唑二基、吡啶二基或嘧啶二基，可选地带有一个或两个卤代、羟基、氨基、硝基、氰基、三氟甲基、C1-4烷基和C1-4烷氧基取代基；R3为以下公式的基团：-A1-Ar2-A2-Y1，其中A1为连接基团-CONHCH（CO2H）的$g(a)-碳原子和Ar2之间的键或C1-2烷基链；Ar2为苯基、四唑二基、噻吩二基、噻唑二基、吡啶二基或嘧啶二基，若为苯基，则可选地在环上带有一个或两个卤代、硝基、C1-4烷基和C1-4烷氧基取代基；A2为C1-3烷基链或C2-3烯基链；以及其药学上可接受的盐或酯，特别是在癌症治疗方面具有治疗价值。