(1S,2S)-2-(methoxycarbonyl)-4-oxocyclopentanecarboxylic acid | 115694-82-1

• 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: (1S,2S)-2-(methoxycarbonyl)-4-oxocyclopentanecarboxylic acid
• 英文别名: trans-2-Methoxycarbonyl-4-oxo-cyclopentanecarboxylic acid；(1S,2S)-2-methoxycarbonyl-4-oxocyclopentane-1-carboxylic acid
• CAS: 115694-82-1
• 化学式: C₈H₁₀O₅
• 分子量: 186.164
• InChiKey: SOSNFEHKRDJYIS-WDSKDSINSA-N

物化性质

• 沸点：
  351.4±42.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S,2S)-2-(methoxycarbonyl)-4-oxocyclopentanecarboxylic acid 在 吡啶 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 phosphate buffer 、 porcine pancreas 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium iodide 作用下， 以 吡啶 、 甲醇 、 乙醚 、 丙酮 、 苯 为溶剂， 反应 60.5h， 生成 Acetic acid (1S,2S)-2-hydroxymethyl-cyclopent-3-enylmethyl ester
  参考文献：
  名称：

  合成前列腺素A2的酶促程序。

  摘要：

  本研究描述了通过酶促反应路线合成前列腺素 A2 (PGA2)的过程。使用酵母或酶对反式-3，4-双（甲氧羰基）环戊酮（1）的对映选择性还原和水解进行了研究，发现通过酶法过程很容易获得(+)-和(-)-1。化合物(+)-1通过猪胰脂肪酶对(+)-二乙酸酯(8)的区域选择性水解，转化为 PGA2 的科里中间体。事实证明，这种基于酶法的合成方法可用于从 (-)-1 合成 PGA 和 PGE。

  DOI：

  10.1248/cpb.36.15
• 作为产物：
  描述：

  trans dimethyl cyclopentanone 3,4-dicarboxylate 在 sodium hydroxide 、 pig liver esterase 作用下， 生成 (1S,2S)-2-(methoxycarbonyl)-4-oxocyclopentanecarboxylic acid
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Aminocyclopentanetricarboxylic Acids:  New Tools to Discriminate between Metabotropic Glutamate Receptor Subtypes

  摘要：

  The four stereoisomers of 1-aminocyclopentane-1,3,4-tricarboxylic acid {ACPT-I (18) and -II (19), (3R,4R)-III [(-)-20], and (3S,4S)-III [(+)-20]} have been synthesized and evaluated for their effects at glutamate receptors subtypes. ACPTs are ACPD analogues in which a third carboxylic group has been added at position 4 in the cyclopentane ring. None of the ACPT isomers showed a significant effect on ionotropic NMDA, KA, and AMPA receptors. On the other hand, ACPT-II (19) was found to be a general competitive antagonist for metabotropic receptors (mGluRs) and exhibited a similar affinity for mGluRla (K-B = 115 +/- 2 mu M), mGluR2 (K-B = 88 +/- 21 mu M), and mGluR4a (K-B = 77 +/- 9 mu M), the representative members-of group I, II and III mGluRs, respectively. Two other isomers, ACPT-I (18) and (+)-(3S,4S)-ACPT-III [(+)-20], were potent agonists at the group III receptor mGluRAa (EC50 = 7.2 +/- 2.3 and 8.8 +/- 3.2 mu M) and competitive antagonists with low affinity for mGluR1a and mGluR2 (K-B > 300 mu M). Finally, (-)-(3R,4R)-ACPT-III [(-)-20] was a competitive antagonist with poor but significant affinity for mGluR4a (K-B = 220 mu M). These results demonstrate that the addition of a third carboxylic group to ACPD can change its activity (from agonist to antagonist) and either increase or decrease its selectivity and/or affinity for the various mGluR subtypes.

  DOI：

  10.1021/jm970207b

文献信息

• [EN] NOVEL HEPATITIS C VIRUS INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：MEDIVIR AB

  公开号：WO2013095275A1

  公开（公告）日：2013-06-27

  The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

  本发明提供了式(I)的化合物：其中环A和A'独立地是5个成员的可选取代的芳香杂环；Q是C(=O)NR1R1'或式U是C(R4)2，O，S，S(=O)2，C(R4)2C(R4)2，CH2O，OCH2，CH2S，SCH2，CH2S(=O)2，S(=O)CH2或C=C(Ru)2；X是CH2，CHR12，CR12R12，O，S，S(=O)2或NRx；m是0，1，2或3；n是0，1，2或3；其他变量如权利要求中所定义，用于治疗或预防丙型肝炎病毒感染，以及相关方面。
• [EN] PROCESSES AND INTERMEDIATES FOR PREPARING A MACROCYCLIC PROTEASE INHIBITOR OF HCV<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES POUR LA PRÉPARATION D'UN INHIBITEUR DE PROTÉASE MACROCYCLIQUE DU VHC
  申请人：JANSSEN PHARMACEUTICALS INC

  公开号：WO2013041655A1

  公开（公告）日：2013-03-28

  Disclosed is a process for the preparation of a cinchonidine salt of formula (IV) via an aqueous solution of a racemic 4-hydroxy-1,2-cyclopentanedicarboxylic acid, which is subjected to cyclization without removing water, by the addition of a water- miscible organic solvent to the aqueous solution and, again without removing water, adding cinchonidine to the aqueous-organic solvent solution so as to obtain the cinchonidine salt of the lactone acid. The cinchonidine salt is allowd to crystallize so as to obtain the enantiomerically purified crystalline lactone acid cinchonidine salt (IV). The enantiomerically pure salt is an intermediate in the synthesis of HCV inhibitor compound of formula (I).

  揭示了一种制备奎宁啉盐（IV式）的过程，通过将外消旋4-羟基-1,2-环戊二羧酸的水溶液进行环化，无需去除水，向水溶液中加入水亲和性有机溶剂，再次无需去除水，将奎宁啉加入水-有机溶剂溶液中，以获得内酯酸奎宁啉盐。奎宁啉盐被允许结晶，以获得对映纯化的结晶内酯酸奎宁啉盐（IV式）。对映纯盐是合成HCV抑制剂化合物（I式）的中间体。
• [EN] PROCESSES AND INTERMEDIATES FOR PREPARING A MACROCYCLIC PROTEASE INHIBITOR OF HCV<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES DE PRÉPARATION D'UN INHIBITEUR DE PROTÉASE MACROCYCLIQUE DE HCV
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2011113859A1

  公开（公告）日：2011-09-22

  A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-(-)- ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-(-)-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-(-)-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis- (1R,2S)-(-)-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-(-)-ephedrine from the precipitated salt obtained in step (b).

  一种制备[(1R,2R)-4-氧代-1,2-环戊二羧酸II的方法，通过拆分外消旋4-氧代-1,2-环戊二羧酸(V)来实现，所述方法包括：(a)将4-氧代-1,2-环戊二羧酸(V)与布鲁辛或(1R,2S)-(-)-麻黄碱反应，从而制备(V)的双布鲁辛盐或双(1R,2S)-(-)-麻黄碱盐，并(b)在(V)的双布鲁辛盐或双(1R,2S)-(-)-麻黄碱盐中选择性地沉淀[(1R,2R)-4-氧代-1,2-环戊二羧酸II的盐，同时(V)的双布鲁辛盐或双(1R,2S)-(-)-麻黄碱盐保持在溶液中；(c)通过从步骤(b)中得到的沉淀盐中去除布鲁辛或(1R,2S)-(-)-麻黄碱来释放酸II。
• Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV
  申请人：Ormerod Dominic John

  公开号：US20130005976A1

  公开（公告）日：2013-01-03

  A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-(−)-ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-(−)-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-(−)-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis-(1R,2S)-(−)-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-(−)-ephedrine from the precipitated salt obtained in step (b).

  一种制备[(1R,2R)-4-氧代-1,2-环戊烷二羧酸II]的方法，通过拆分混合物中的4-氧代-1,2-环戊烷二羧酸(V)得到，该方法包括：(a)将4-氧代-1,2-环戊烷二羧酸(V)与金雀碱或(1R,2S)-(-)-麻黄碱反应，从而制备出(V)的双金雀碱或双(1R,2S)-(-)-麻黄碱盐，(b)有选择地沉淀(1R,2R)-4-氧代-1,2-环戊烷二羧酸II的双金雀碱或双(1R,2S)-(-)-麻黄碱盐，而双金雀碱或双(1R,2S)-(-)-麻黄碱盐的[(1S,2S)-4-氧代-1,2-环戊烷二羧酸]保持在溶液中；(c)通过从步骤(b)中沉淀的盐中去除金雀碱或(1R,2S)-(-)-麻黄碱来释放酸II。
• Stereoselective Total Synthesis of (−)-Borrelidin
  作者：Binh G. Vong、Sun Hee Kim、Sunny Abraham、Emmanuel A. Theodorakis

  DOI：10.1002/anie.200460203

  日期：2004.7.26