(2R,3R)-(-)-diethyl aziridine-2,3-dicarboxylate | 168113-12-0

• 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: (2R,3R)-(-)-diethyl aziridine-2,3-dicarboxylate
• 英文别名: diethyl (2R,3R)-aziridine-2,3-dicarboxylate
• CAS: 168113-12-0
• 化学式: C₈H₁₃NO₄
• mdl: MFCD19686506
• 分子量: 187.196
• InChiKey: ZDCRASVHGJDHRS-PHDIDXHHSA-N

物化性质

• 沸点：
  259.2±40.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  74.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3R)-(-)-diethyl aziridine-2,3-dicarboxylate 在 palladium on activated charcoal 氢气 、 sodium carbonate 、 potassium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 (2R,3R) 2-[2,3-bis(ethoxycarbonyl)aziridine-1-yl]acetic acid
  参考文献：
  名称：

  aziridinyl peptides as inhibitors of cysteine proteases: Effect of a free carboxylic acid function on inhibition

  摘要：

  Peptides containing aziridine-2,3-dicarboxylate (Azi) as electrophilic building block are evaluated as inhibitors of the cysteine proteases papain, cathepsin B, cathepsin L and clostripain. The influence of a free carboxylic acid as functional group at different positions of the inhibitor molecule on inhibition is analyzed. Structure-activity relationships and binding mode hypotheses are discussed. In contrast to the bacterial enzyme clostripain, the papain like mammalian proteases (cathepsins) are irreversibly inactivated by aziridinyl peptides. N-Unsubstituted aziridines are much more potent inhibitors of papain and cathepsins if they contain the free carboxylic acid attached to the aziridine ring (HOAzi-Leu-ProOBzl). Two free carboxylic acid functions at the aziridine ring are necessary for good inhibition of these enzymes by N'-acylated aziridinyl peptides (BOC-Phe-Azi(OH)(2)). Chimeric bispeptidyl derivatives are selective CB inhibitors if the free acid is located at the C-terminus of the peptide (BOC-Phe-(EtO)Azi-Leu-ProOH). Clostripain is only inhibited by aziridinyl peptide esters. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00058-4
• 作为产物：
  描述：

  L-(+)-酒石酸二乙酯 在 sodium azide 、 三乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (2R,3R)-(-)-diethyl aziridine-2,3-dicarboxylate
  参考文献：
  名称：

  3-氟氨基酸的立体定向放射合成：使用对映体纯的放射性配体进行正电子发射断层扫描†

  摘要：

  制备了多种等效于氨基酸的取代的非外消旋氮丙啶-2-羧酸盐，并通过[ 18 F / 19 F]氟化物进行开环反应。区域和立体特异性开环取决于氮上的取代基以及氮丙啶的两个碳。说明了提供接近3- [ 18 F / 19 F]氟氨基酸的方法的适用性。

  DOI：

  10.1039/c8ob00184g

文献信息

• Aziridine-2,3-dicarboxylic Acid Derivatives as Inhibitors of Papain
  作者：Tanja Schirmeister

  DOI：10.1002/ardp.19963290504

  日期：——

  Aziridine‐2,3‐dicarboxylates and N‐acylated derivatives have been evaluated as potential irreversible inhibitors of the cysteine proteinase papain. Dependence of inhibition activity on stereo‐chemistry of the aziridine moiety has been analyzed. Whereas unsubstituted (R,R)‐ and (S,S)‐ diethyl aziridine‐2,3‐dicarboxylates (5) and (2) show no significant difference in inactivation the derivative acylated

  Aziridine-2,3-dicarboxylates 和 N-acylated 衍生物已被评估为半胱氨酸蛋白酶木瓜蛋白酶的潜在不可逆抑制剂。已经分析了抑制活性对氮丙啶部分立体化学的依赖性。而未取代的 (R,R)- 和 (S,S)- 二乙基氮丙啶-2,3-二羧酸酯 (5) 和 (2) 在钝化 BOC-(S)-Phe (BOC- (S)-Phe-(S,S)-Azi) (10) 的活性比非对映异构体 BOC-(S)-Phe-(R,R)-Azi (11) 高 6 倍。用 Z- 或 BOC-(S)-Ala (9, 8) 酰化的类似物具有较低的二级速率常数，表明抑制剂的氨基酸部分与酶的 S2 亚位点结合。
• An improved synthesis of aziridine-2,3-dicarboxylates via azido alcohols—epimerization studies
  作者：Alexander Breuning、Radim Vicik、Tanja Schirmeister

  DOI：10.1016/j.tetasy.2003.09.015

  日期：2003.10

  pure trans-aziridine-2,3-dicarboxylates for which an optimized synthetic pathway is presented. The first example of an enantiomerically pure mixed diester of the aziridine-2,3-dicarboxylic acid the synthesis of the allyl ethyl ester is reported herein.

  现在阐明在环氧化物或环亚硫酸盐与叠氮化钠开环期间观察到的3-叠氮基-2-羟基琥珀酸酯差向异构化的原因。这是由于质子在3位的高酸度引起的。通过在含有D 2 O或DC1的溶剂中进行质子氘交换，可以证明这一点。所述抗-3-叠氮基-2- hydroxysuccinates用作中间体对映体纯的反式针对其优化的合成途径被呈现-吖丙啶-2,3-二羧酸酯。本文报道了氮丙啶-2，3-二羧酸的对映体纯的混合二酯的第一个实例，烯丙基乙基酯的合成。
• New Peptidic Cysteine Protease Inhibitors Derived from the Electrophilic α-Amino Acid Aziridine-2,3-dicarboxylic Acid
  作者：Tanja Schirmeister

  DOI：10.1021/jm981061z

  日期：1999.2.1

  bispeptidyl derivatives of Azi) have been synthesized and tested as inhibitors of the cysteine proteases papain, cathepsins B, L, and H, and calpains I and II, as well as against several serine proteases, one aspartate, and one metalloprotease. All aziridinyl peptides are specific cysteine protease inhibitors. Papain and cathepsins B and L are inhibited irreversibly, whereas cathepsin H and calpains

  三种不同类型的肽，在其肽链的不同位置上含有氮丙啶-2、3-二羧酸（Azi）作为亲电子的α-氨基酸（I型，N-酰化氮丙啶，Azi作为C末端氨基酸； II型，已合成了以Azi为N末端氨基酸的N-未取代的氮丙啶； III型，Azi的N-酰化双肽基衍生物），并已作为半胱氨酸蛋白酶木瓜蛋白酶，组织蛋白酶B，L和H以及钙蛋白酶I和I的抑制剂进行了测试。 II，以及针对几种丝氨酸蛋白酶，一种天冬氨酸和一种金属蛋白酶。所有的氮丙啶基肽都是特定的半胱氨酸蛋白酶抑制剂。木瓜蛋白酶和组织蛋白酶B和L被不可逆地抑制，而组织蛋白酶H和钙蛋白酶以非时间依赖性方式被抑制。某些化合物被证明是丝氨酸蛋白酶和金属蛋白酶嗜热菌蛋白酶的底物。可以观察到三种不同类型的抑制剂之间的显着差异，包括立体特异性，抑制的pH依赖性，不同的半胱氨酸蛋白酶之间的选择性以及在氮丙啶环上的游离羧酸功能对于抑制的重要性。首先，II型抑制剂是众所周知的
• Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases
  作者：Caroline Schad、Ulrike Baum、Benjamin Frank、Uwe Dietzel、Felix Mattern、Carlos Gomes、Alicia Ponte-Sucre、Heidrun Moll、Uta Schurigt、Tanja Schirmeister

  DOI：10.1128/aac.00426-15

  日期：2016.2

  Leishmaniasis is one of the major neglected tropical diseases of the world. Druggable targets are the parasite cysteine proteases (CPs) of clan CA, family C1 (CAC1). In previous studies, we identified two peptidomimetic compounds, the aziridine-2,3-dicarboxylate compounds 13b and 13e, in a series of inhibitors of the cathepsin L (CL) subfamily of the papain clan CAC1. Both displayed antileishmanial activityin vitrowhile not showing cytotoxicity against host cells. In further investigations, the mode of action was characterized inLeishmania major. It was demonstrated that aziridines 13b and 13e mainly inhibited the parasitic cathepsin B (CB)-like CPC enzyme and, additionally, mammalian CL. Although these compounds induced cell death ofLeishmaniapromastigotes and amastigotesin vitro, the induction of a proleishmanial T helper type 2 (Th2) response caused by host CL inhibition was observedin vivo. Therefore, we describe here the synthesis of a new library of more selective peptidomimetic aziridine-2,3-dicarboxylates discriminating between host and parasite CPs. The new compounds are based on 13b and 13e as lead structures. One of the most promising compounds of this series is compound s9, showing selective inhibition of the parasite CPsLmaCatB (a CB-like enzyme ofL. major; also namedL. majorCPC) andLmCPB2.8 (a CL-like enzyme ofLeishmania mexicana) while not affecting mammalian CL and CB. It displayed excellent leishmanicidal activities againstL. majorpromastigotes (50% inhibitory concentration [IC₅₀] = 37.4 μM) and amastigotes (IC₅₀= 2.3 μM). In summary, we demonstrate a new selective aziridine-2,3-dicarboxylate, compound s9, which might be a good candidate for futurein vivostudies.

  摘要 利什曼病是世界上被忽视的主要热带疾病之一。寄生虫半胱氨酸蛋白酶（CPs）是CA家族C1（CAC1）的可药用靶标。在之前的研究中，我们在木瓜蛋白酶家族 CAC1 的酪蛋白酶 L（CL）亚家族的一系列抑制剂中发现了两种拟肽化合物，即氮丙啶-2,3-二羧酸化合物 13b 和 13e。这两种化合物在体外都显示出抗利什曼病活性，但对宿主细胞没有细胞毒性。在进一步的研究中，对其在利什曼原虫中的作用模式进行了鉴定。结果表明，氮丙啶 13b 和 13e 主要抑制寄生虫的类似于 CB 的 CPC 酶，此外还抑制哺乳动物的 CL。虽然这些化合物能在体外诱导利什曼病原虫和非原虫的细胞死亡，但在体内却观察到宿主的 CL 抑制作用诱导了原利什曼病 T 辅助细胞 2 型（Th2）反应。因此，我们在此描述了一个新的肽拟氮丙啶-2,3-二羧酸盐库的合成过程，该库具有更高的选择性，可区分宿主和寄生虫 CPs。新化合物以 13b 和 13e 为先导结构。该系列中最有前途的化合物之一是化合物 s9，它对寄生虫 CPsLmaCatB（大头利什曼原虫的一种 CB 类酶；也称为大头利什曼原虫 CPC）和 LmCPB2.8（墨西哥利什曼原虫的一种 CL 类酶）具有选择性抑制作用，而对哺乳动物的 CL 和 CB 没有影响。它对L. majorpromastigotes（50%抑制浓度 [IC50] = 37.4 μM）和amastigotes（IC50= 2.3 μM）显示出卓越的杀利什曼活性。总之，我们证明了一种新的选择性氮丙啶-2,3-二羧酸盐--化合物 s9，它可能是未来活体研究的良好候选药物。
• Antibiotic derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0219923A1

  公开（公告）日：1987-04-29

  The compound represented by the formula: where R' stands for amino or an organic residue bonded through nitrogen; R2 stands for carooxyl ora group derivable therefrom; R3, R4, R5, R6, R7 and R8 independently stand for hydrogen or an organic residue, including the case where R5 or R6 forms a chemical bond or a ring with R7 or R8: X stands for hvdrogen, methoxy or formylamino; or a salt thereof, pro- duceaole by the present method. exnibits excellent antimicrobial activity, and is utilized as antimicrobial agents.

  式所代表的化合物： 其中，R'代表氨基或通过氮键结合的有机残基；R2代表甲氧羰基或可由其衍生的基团；R3、R4、R5、R6、R7 和 R8 分别代表氢或有机残基，包括 R5 或 R6 与 R7 或 R8 形成化学键或环状的情况：X 代表氢、甲氧基或甲酰氨基；或其盐，通过本方法制得。它们具有优异的抗菌活性，可用作抗菌剂。