(2R,3R)-3-乙氧羰基环氧乙烷-2-羧酸 | 93061-20-2

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环氧化物
• 中文名称: (2R,3R)-3-乙氧羰基环氧乙烷-2-羧酸
• 中文别名: (2R,3R)-3-乙氧羰基-环氧乙烷-2-羧酸
• 英文名称: (2R,3R)-3-(ethoxycarbonyl)oxirane-2-carboxylic acid
• 英文别名: (2R,3R)-3-ethoxycarbonyloxirane-2-carboxylic acid
• CAS: 93061-20-2
• 化学式: C₆H₈O₅
• 分子量: 160.127
• InChiKey: MWMZDXCRDIBPCO-QWWZWVQMSA-N

物化性质

• 沸点：
  278.9±40.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2918990090
• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  (2R,3R)-3-乙氧羰基环氧乙烷-2-羧酸 生成 L-threo-BocNH-β-OH-Asn
  参考文献：
  名称：

  KISIMOTO, SEDZI;TISIRO, MITIYUKI;OTIAI, MITIXIKO

  摘要：

  DOI：
• 作为产物：
  描述：

  L-(+)-酒石酸二乙酯 在 氢溴酸 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 potassium hydroxide 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 26.5h， 生成 (2R,3R)-3-乙氧羰基环氧乙烷-2-羧酸
  参考文献：
  名称：

  Design, Synthesis, and Optimization of Novel Epoxide Incorporating Peptidomimetics as Selective Calpain Inhibitors

  摘要：

  Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Call) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Call. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Call catalytic domain (Call(cat)), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Call inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Call with the genera l cysteine protease papain.

  DOI：

  10.1021/jm4006719

文献信息

• Aza-Peptide Epoxides:  A New Class of Inhibitors Selective for Clan CD Cysteine Proteases
  作者：Juliana L. Asgian、Karen Ellis James、Zhao Zhao Li、Wendy Carter、Alan J. Barrett、Jowita Mikolajczyk、Guy S. Salvesen、James C. Powers

  DOI：10.1021/jm025581c

  日期：2002.11.1

  Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M(-1) s(-1), with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition

  氮杂肽环氧化物是一类新的不可逆的蛋白酶抑制剂，对氏族CD半胱氨酸蛋白酶具有特异性。抑制剂具有高达10（5）M（-1）s（-1）的二阶速率常数，最有效的环氧化物具有S，S立体化学。氮杂-Asn衍生物是有效的豆蔻蛋白酶抑制剂，而氮杂-Asp环氧化物对胱天蛋白酶具有特异性。抑制剂对其他蛋白酶（如胰凝乳蛋白酶，木瓜蛋白酶或组织蛋白酶B）几乎没有抑制作用。
• Konfiguration und enantioselektive Synthese des Pilzmetaboliten WF14861
  作者：Richard Detterbeck、Manfred Hesse

  DOI：10.1002/hlca.200390015

  日期：2003.1

  A short enantioselective synthesis of the cathepsine inhibitor WF14861 (1) from the funghi Colletotrichum sp. as well as of its diasteroisomer 21 is presented. Comparison of the NMR data of the final products and, in particular, of the [α]D values of the intermediates allowed the confirmation of the formerly proposed structure 1. In addition, the so far unknown absolute configuration of all three stereogenic

  从Funghi Colletotrichum sp。短时对映体合成组织蛋白酶抑制剂WF14861（1）。以及它的非对映异构体21。通过比较最终产物的NMR数据，尤其是中间体的[ α ] D值，可以确认先前提出的结构1。另外，通过该合成可以建立迄今未知的WF14861的所有三个立体异构中心的绝对构型。
• [EN] PYRIDOPYRIMIDINE DERIVATIVES USEFUL AS KRAS G12C AND KRAS G12D INHIBITORS IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE PYRIDOPYRIMIDINE UTILES EN TANT QU'INHIBITEURS DE KRAS G12C ET DE KRAS G12D DANS LE TRAITEMENT DU CANCER
  申请人：AMGEN INC

  公开号：WO2021081212A1

  公开（公告）日：2021-04-29

  Provided herein are KRAS G12C and KRAS G12D inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

  本文提供了KRAS G12C和KRAS G12D抑制剂，其组成，以及使用这些抑制剂的方法。这些抑制剂对治疗多种疾病有用，包括胰腺癌、结直肠癌和肺癌。
• Efficient synthetic method for ethyl (+)-(2S,3S)-3-((S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl)-2-oxiranecarboxylate (EST), a new inhibitor of cysteine proteinases.
  作者：MASAHARU TAMAI、CHIHIRO YOKOO、MITSUO MURATA、KIYOSHI OGUMA、KAORU SOTA、EISUKE SATO、YUICHI KANAOKA

  DOI：10.1248/cpb.35.1098

  日期：——

  Ethly (+)-(2S, 3S) -3- [(S) -3-methyl-1- (3-methylbutylcarbamoyl) butylcarbamoyl] -2- oxirane-carboxylate (EST ; la) is expected to be useful as an oral therapeutic agent for muscular dystrophy on the basis of its potent inhibitory activities against the cysteine proteinases involved in the myofibrillar protein degradation that occurs in the disease. Through extensive investigations aimed at developing a new synthetic method for la that would be suitable for industrial application, it has been found that L-arginine can be used as a new, efficient resolving agent to obtain optically pure L-trans-epoxysuccinic acid (3a), and the active ester method using p-nitrophenol is very effective in the coupling reaction of ethyl L-trans-epoxysuccinate (7a) and L-leucine isoamylamide (8a) because of the extremely low formation of by-products. To examine the contribution of the stereochemistry of the trans-epoxysuccinic acid and leucine moieties to the inhibitory activity against cysteine proteinases, the diastereomers (lb-d) of la were synthesized by a similar method and the rate constants of inactivation of papain by la-d were measured. Compound la, having L-trans-epoxysuccinic acid and L-leucine moieties, showed the most potent activity among them.

  Ethly (+)-(2S, 3S)-3-[(S)-3-甲基-1-(3-甲基丁基氨基甲酰基)丁基氨基甲酰基]-2-环氧羧酸酯（EST；la）预计将作为治疗肌肉萎缩症的口服药物，因为它对与疾病相关的肌纤维蛋白降解中涉及的半胱氨酸蛋白酶具有强大的抑制活性。通过广泛的研究，旨在开发一种适用于工业应用的新合成方法，发现L-精氨酸可以作为新的高效分离剂，用于获得光学纯的L-反-环氧富马酸（3a），而使用对硝基苯酚的活性酯方法在乙基L-反-环氧富马酸（7a）和L-亮氨酸异戊酰胺（8a）之间的偶联反应中非常有效，因为副产物的生成极少。为了检查反-环氧富马酸和亮氨酸部分的立体化学对半胱氨酸蛋白酶抑制活性的贡献，采用类似的方法合成了la的二叠体（lb-d），并测量了la-d对木瓜蛋白酶的灭活速率常数。化合物la，具有L-反-环氧富马酸和L-亮氨酸部分，显示出其中最强的活性。
• Syntheses of (4,1-Benzoxazepine-3-ylidene)acetic Acid Derivatives and Their Inhibition of Squalene Synthase.
  作者：Takashi Miki、Masakuni Kori、Ryu-ichi Tozawa、Masahira Nakamura、Yasuo Sugiyama、Hidefumi Yukimasa

  DOI：10.1248/cpb.50.53

  日期：——

  The (3,5-trans)-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid derivatives 1 have been previously identified as potent squalene synthase inhibitors. A series of (4,1-benzoxazepin-3-ylidene)acetic acid derivatives were synthesized and evaluated for their inhibition of rat and human squalene synthase, and the (E)-isomers were found to exhibit potent inhibitory activity, with the same potency as 4,1-benzoxazepine-3-acetic acid derivatives. In contrast the (Z)-isomers did not exhibit significant inhibitory activity, and the active conformation of the 4,1-benzoxazepine-3-acetic acid derivatives was deduced from the folded conformation of the (E)-isomers.

  (3,5-trans)-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid derivatives 1 以前曾被鉴定为有效的角鲨烯合成酶抑制剂。研究人员合成了一系列（4,1-苯并氧氮杂卓-3-亚基）乙酸衍生物，并评估了它们对大鼠和人类角鲨烯合成酶的抑制作用，结果发现(E)-异构体具有强效的抑制活性，其效力与 4,1-苯并氧氮杂卓-3-乙酸衍生物相同。相反，(Z)-异构体没有表现出明显的抑制活性，而 4,1-苯并氧氮杂卓-3-乙酸衍生物的活性构象是根据(E)-异构体的折叠构象推断出来的。