3-hydroxy-5-methoxy-3-(methoxycarbonyl)-5-oxopentanoic acid | 53798-97-3

• 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: 3-hydroxy-5-methoxy-3-(methoxycarbonyl)-5-oxopentanoic acid
• 英文别名: dimethyl citrate；(R)-3-Hydroxy-5-methoxy-3-(methoxycarbonyl)-5-oxopentanoic acid；3-hydroxy-5-methoxy-3-methoxycarbonyl-5-oxopentanoic acid
• CAS: 53798-97-3
• 化学式: C₈H₁₂O₇
• 分子量: 220.179
• InChiKey: OMIHCBSQSYMFDP-UHFFFAOYSA-N

物化性质

• 保留指数：
  1563

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-hydroxy-5-methoxy-3-(methoxycarbonyl)-5-oxopentanoic acid 在 氯化亚砜 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 7.25h， 生成 2-(2-(((R)-2,3-dihydro-1H-inden-1-yl)(prop-2-ynyl)amino)-2-oxoethyl)-2-hydroxysuccinic acid
  参考文献：
  名称：

  RASAGILINE CITRAMIDE

  摘要：

  该发明提供了拉沙吉林柠檬酰胺和含有N-丙炔基-1(R)-氨基茚或其药用可接受盐的组合物，以及拉沙吉林柠檬酰胺化合物或其盐。

  公开号：

  US20130089611A1
• 作为产物：
  描述：

  柠檬酸三甲酯 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以57%的产率得到3-hydroxy-5-methoxy-3-(methoxycarbonyl)-5-oxopentanoic acid
  参考文献：
  名称：

  A FACILE PREPARATION OFASYM-MONOMETHYL,SYM-MONOMETHYL ANDASYM-DIMETHYL CITRATE

  摘要：

  非对称单甲基柠檬酸是通过对称二甲基柠檬酸的水解制备的。对称单甲基和非对称二甲基柠檬酸是通过对三甲基柠檬酸的选择性水解制备的。

  DOI：

  10.1246/cl.1980.191

文献信息

• PROCESS FOR PREPARING CEPHALOTAXINE ESTERS
  申请人：Robin Jean-Pierre

  公开号：US20120022250A1

  公开（公告）日：2012-01-26

  A process for preparing cephalotaxine esters corresponding to the following general formula I which comprises the cephalotaxine backbone: C(R 1 )(R 2 )(XH)COO[CTX] wherein CTX represents the cephalotaxine backbone, being optionally substituted and/or dehydrogenated, in which formula I, X is a heteroatom, preferably an oxygen, a sulfur or a nitrogen, R 1 and R 2 , taken separately, may be alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl, heterocycloalkyl or aralkyl groups, said groups being optionally interrupted by ester functions, or groups that can form one or more rings or a heterocycle together, consisting in bringing the corresponding cephalotaxine compound, or salts, isomers or tautomeric forms thereof, which is free or which is in the form of a metal alkoxide corresponding to the following general formula CTXOM, wherein CTX represents the cephalotaxine backbone, being optionally substituted and/or dehydrogenated, in which M is a hydrogen atom or a metal atom, into contact with a heterocyclic side chain precursor having both a bifunctional protected (bidentate) and activated (acylating) form of an acid bearing a hydrogenated heteroatom, in the alpha (α) position with respect to the carboxyl group, and corresponding to the following general formula: in which case W is a carbon, sulfur, silicon or bore atom, X, R 1 and R 2 have respectively the same meaning as above, it being possible for R 1 and R 2 to form a ring or a heterocycle together, and Y and Z are alkyl or heteroalkyl radicals, or monovalent heteroatoms, which may be identical or different, in an independent manner, or may fuse so as to give a divalent heteroatom, it being possible for the X—W bond to be covalent or ionic.

  一种制备对应以下一般式I的头叶松碱酯的方法，其中包括头叶松碱骨架：C(R1)(R2)(XH)COO[CTX]，其中CTX代表头叶松碱骨架，可以是可选择地取代和/或脱氢的，在该式I中，X是一个杂原子，优选为氧、硫或氮，R1和R2，分别取，可以是烷基、环烷基、杂基、芳基、杂芳基、杂环烷基或芳基，这些基团可以通过酯功能团中断，或者可以形成一个或多个环或一个杂环，包括将相应的头叶松碱化合物，或其盐、异构体或互变异构体形式，该化合物是自由的或以金属烷氧基的形式存在，对应以下一般式CTXOM，其中CTX代表头叶松碱骨架，可以是可选择地取代和/或脱氢的，在该式中，M是氢原子或金属原子，与具有双功能保护（双齿）和活化（酰化）形式的酸的α位上带有氢杂原子的杂环侧链前体接触，该酸与羧基相对应，并对应以下一般式：在这种情况下，W是碳、硫、硅或硼原子，X、R1和R2分别具有与上述相同的含义，R1和R2可以共同形成一个环或一个杂环，Y和Z是烷基或杂基基，或一价杂原子，可以独立地相同或不同，或者可以融合以形成二价杂原子，X—W键可以是共价键或离子键。
• The design and synthesis of nucleoside triphosphate isosteres as potential inhibitors of HIV reverse transcriptase
  作者：Richard Weaver、Ian H. Gilbert

  DOI：10.1016/s0040-4020(97)00210-x

  日期：1997.4

  describe the synthesis of a variety of lipophilic isosteres of nucleoside triphosphates as potential anti-HIV agents. The citrate molecule proved to be a good mimic of triphosphate by modelling in terms of charge and spatial distribution. Several lipophilc derivatives of citrate were conjugated to the precedented anti-HIV nucleoside d4T via ester and amide linkages. A novel synthesis of 5′-amino-d4T

  我们描述了作为潜在的抗艾滋病毒药物的核苷三磷酸的各种亲脂性等排体的合成。通过在电荷和空间分布方面进行建模，证明柠檬酸盐分子是三磷酸的良好模拟物。几种柠檬酸酯的亲脂性衍生物通过酯和酰胺键与先前的抗HIV核苷d4T缀合。包括5'-氨基-d4T的新合成。还报道了几种酰胺连接的等排物的分子内重排，以及对于所需酰胺连接的等排物的替代合成策略。
• [EN] METHOD FOR THE PRODUCTION OF METHYLSUCCINIC ACID AND THE ANHYDRIDE THEREOF FROM CITRIC ACID<br/>[FR] PROCÉDÉ DE PRODUCTION D'ACIDE MÉTHYLSUCCINIQUE ET DE SON ANHYDRIDE À PARTIR D'ACIDE CITRIQUE
  申请人：UNIV LEUVEN KATH

  公开号：WO2018065475A1

  公开（公告）日：2018-04-12

  A process for the preparation of methylsuccinic acid in any form, including its salts, its mono- and diester derivatives and the anhydride thereof, which comprises reacting citric acid or a derivative thereof in decarboxylation conditions, said process comprising (i) reacting citric acid or mono- and diester derivatives thereof in a non- aqueous solvent, specifically excluding alcohols, on a metallic catalyst at a temperature between 50 to 400°C and under a partial hydrogen pressure from 0.1 to 50 bar or (ii) reacting citric acid or any salt thereof or mono-, di- and triester derivatives thereof on a metallic catalyst in solvents comprising at least 5% water, at a temperature of from 50 to 400°C under a hydrogen partial pressure from 0.1 to 400 bar

  一种制备甲基琥珀酸及其盐、单酯和二酯衍生物以及其酐的方法，包括在脱羧条件下反应柠檬酸或其衍生物，所述方法包括(i) 在非水溶剂中在金属催化剂上以50至400°C的温度和0.1至50巴的部分氢压力下反应柠檬酸或其单酯和二酯衍生物，特别排除醇；或(ii) 在含水量至少为5%的溶剂中，在50至400°C的温度下，在0.1至400巴的氢分压下反应柠檬酸或其任何盐或其单酯、二酯和三酯衍生物上。
• CGRP ANALOG
  申请人：Southard George Lee

  公开号：US20110150980A1

  公开（公告）日：2011-06-23

  Sequence modified calcitonin gene related peptide (CGRP) compounds are useful for treating heart failure, stroke, hemorrhagic shock, or migraine, improving renal function, preventing or delaying the advancement of heart failure into advanced stages, treating angina, controlling pulmonary hypertension, counteracting ischemia due to a myocardial infarction, preventing vasospasms during angioplasty, preventing reocclusion of blood vessels during and/or after angioplasty, stent insertion, or the implantation of a vascular grafts, and for treating male impotence and female sexual arousal disorder.

  序列改良的降钙素基因相关肽（CGRP）化合物可用于治疗心力衰竭、中风、出血性休克或偏头痛，改善肾功能，预防或延缓心力衰竭进展至晚期阶段，治疗心绞痛，控制肺动脉高压，对抗心肌梗死引起的缺血，预防在血管成形术期间发生血管痉挛，预防在血管成形术期间和/或之后血管再闭塞，支架植入或血管移植物植入，以及治疗男性阳痿和女性性唤醒障碍。
• Staphyloferrin A as siderophore-component in fluoroquinolone-based Trojan horse antibiotics
  作者：Stephen J. Milner、Alexandra Seve、Anna M. Snelling、Gavin H. Thomas、Kevin G. Kerr、Anne Routledge、Anne-Kathrin Duhme-Klair

  DOI：10.1039/c3ob40162f

  日期：——

  A series of fluoroquinolone conjugates was synthesised by linking the carboxylic acid functionality of the carboxylate-type siderophore staphyloferrin A and its derivatives to the piperazinyl nitrogen of ciprofloxacin and norfloxacin via amide bond formation. Four siderophore–drug conjugates were screened against a panel of bacteria associated with infection in humans. Whilst no activity was found against ciprofloxacin- or norfloxacin-resistant bacteria, one of the conjugates retained antibacterial activity against fluoroquinolone-susceptible strains although the structure of its lysine-based siderophore component differs from that of the natural siderophore staphyloferrin A. In contrast, three ornithine-based siderophore conjugates showed significantly reduced activity against strains that are susceptible to their respective parent fluoroquinolones, regardless of the type of fluoroquinolone attached or chirality at the ornithine Cα-atom. The loss of potency observed for the (R)- and (S)-ornithine-based ciprofloxacin conjugates correlates with their reduced inhibitory activity against the target enzyme DNA gyrase.

  一系列氟喹诺酮类缀合物通过将羧酸盐型铁载体分子的羧酸功能基团——葡萄球菌素A及其衍生物与环丙沙星和诺氟沙星的哌嗪基氮原子通过酰胺键连接而合成。筛选了四种铁载体-药物缀合物对与人类感染相关的一组细菌的作用。尽管对耐环丙沙星或诺氟沙星的细菌没有活性，但其中一个缀合物仍保留了对氟喹诺酮敏感菌株的抗菌活性，尽管其赖氨酸基铁载体部分的结构与天然铁载体葡聚糖素A不同。相比之下，三种鸟氨酸基铁载体缀合物对其各自母体氟喹诺酮敏感菌株的活性显著降低，不论所连接的氟喹诺酮类型或鸟氨酸Cα原子上的手性如何。观察到的(R)-和(S)-鸟氨酸基环丙沙星缀合物的效价损失与其对目标酶DNA促旋酶的抑制活性降低相关。