(1RS,2SR)-1-hydroxy-butane-1,2,4-tricarboxylic acid | 3562-75-2

• 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: (1RS,2SR)-1-hydroxy-butane-1,2,4-tricarboxylic acid
• 英文别名: (+/-)-1r_F-Hydroxy-butan-1cat_F,2t_F,4-tricarbonsaeure；(1RS,2SR)-1-Hydroxy-butan-1,2,4-tricarbonsaeure；Homoisocitronensaeure；rac. threo-Homoisocitronensaeure；(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylic acid
• CAS: 3562-75-2；26091-87-2；26091-88-3；26091-89-4；26097-12-1；56298-34-1
• 化学式: C₇H₁₀O₇
• 分子量: 206.152
• InChiKey: OEJZZCGRGVFWHK-WVZVXSGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  7

安全信息

• 海关编码：
  2918199090

反应信息

• 作为反应物：
  描述：

  (1RS,2SR)-1-hydroxy-butane-1,2,4-tricarboxylic acid 在 homoisocitrate dehydrogenase from Thermus thermophilus 、 β-烟酰胺腺嘌呤二核苷酸 作用下， 以 aq. buffer 为溶剂， 生成 2-氧代己二酸
  参考文献：
  名称：

  双重底物特异性的决定因素是由嗜热栖热菌的均异柠檬酸脱氢酶与均异柠檬酸·Mg（2+）·NADH复合形成的。

  摘要：

  HICDH（纯异柠檬酸脱氢酶）是β-脱羧脱氢酶家族的成员，它使用NAD（+）作为辅酶催化纯异柠檬酸转化为α-酮己二酸酯，这是涉及通过α-氨基己二酸途径进行赖氨酸生物合成的第四反应。尽管来自真菌和酵母菌的典型HICDHs对均同柠檬酸盐（HIC）表现出严格的底物特异性，但来自嗜热嗜热菌（Thermus thermophilus）（TtHICDH）的HICDH仍以HIC和异柠檬酸盐（IC）作为底物以相似的效率催化反应。我们在本文中以2.5的分辨率确定了TtHICDH与HIC，NADH和Mg（2+）离子的季铵盐配合物的晶体结构。结构表明，HIC的远端羧基被一个亚基的Ser72和Arg85的侧链识别，来自二聚体单元另一个亚基的Asn173。构建了与IC配合使用的TtHICDH和与HIC配合使用的酿酒酵母（ScHICDH）的HICDH的模型结构。TtHICDH通过模型中的Arg85识别IC的远端羧基。

  DOI：

  10.1016/j.bbrc.2016.09.004
• 作为产物：
  描述：

  methyl 2-acetoxy-3-carbomethoxy-6-(phenylthio)-5-hexynoate 在 DOWEX 50X resin H⁺ 20percent HgSO₄ 作用下， 以 水 为溶剂， 反应 72.0h， 以76%的产率得到(1RS,2SR)-1-hydroxy-butane-1,2,4-tricarboxylic acid
  参考文献：
  名称：

  （-）-异柠檬酸内酯和（-）-同异柠檬酸的合成。将炔基硅烷转化为炔基硫醚和相应羧酸的新方法。

  摘要：

  从常见的炔基硅烷简单，立体选择性地合成天然异构酸和均异构酸与这些酸的立体化学相关。从D-苹果酸二甲酯二价阴离子开始，制备2-羟基-3-羰基甲氧基-6-（三甲基甲硅烷基）-5-己酸甲酯（6a），并具有良好的立体选择性（苏/赤90/10）。从D-苹果酸二酯1开始，三键的氧化裂解以15％的总收率提供了异​​柠檬酸内酯（8'）。合成高柠檬酸的方法依赖于将炔基硅烷转化为炔基硫醚的新方法，然后将其转化为相同链长的羧酸。将苯磺酰氯加到（三甲基甲硅烷基）炔烃6b中，消除三甲基甲硅烷基氯，得到相应的硫醚10，通过酸水解将其从D-苹果酸酯中以24％的收率得到高同二十二酸（11）。用其他几种炔基三甲基硅烷说明了将炔基硅烷转化为相应酸的新方法。

  DOI：

  10.1021/jo951062o

文献信息

• Short and efficient syntheses of (−) -isocitric acid lactone and (−) -homoisocitric acid. Conversion of alkynylsilanes into the corresponding carboxylic acids
  作者：Carole Schmitz、Anne-Claire Rouanet-Dreyfuss、Marie Tueni、Jean-François Biellman

  DOI：10.1016/s0040-4039(00)61231-5

  日期：1992.8

  We describe a simple synthesis of natural isocitric and homoisocitric acids from a common intermediate 2. A new method of conversion from a silylated triple bond to the carboxylic acid of the same chain length has been formulated.

  我们描述了从常见的中间体2简单合成天然的isotricic和homisoocitricic酸。已制定了一种从甲硅烷基化的三键转换为相同链长的羧酸的新方法。
• Substrate specificity analysis and inhibitor design of homoisocitrate dehydrogenase
  作者：Takashi Yamamoto、Kentaro Miyazaki、Tadashi Eguchi

  DOI：10.1016/j.bmc.2006.11.008

  日期：2007.2.1

  as a coenzyme. Substrate specificity of two homoisocitrate dehydrogenases derived from Deinococcus radiodurans and Saccharomyces cerevisiae was analyzed using a series of synthetic substrate analogs, which indicated a relatively broad substrate specificity of these enzymes. Based on the substrate specificity, 3-hydroxyalkylidene- and 3-carboxyalkylidenemalate derivatives were designed as a specific

  同异柠檬酸脱氢酶参与真菌，酵母，某些原核细菌和古细菌中l-赖氨酸生物合成的α-氨基己二酸途径。该酶使用NAD（+）作为辅酶催化（2R，3S）-高异柠檬酸的氧化脱羧成2-氧代己二酸酯。使用一系列合成的底物类似物分析了源自Deinococcus radiodurans和酿酒酵母的两种均异柠檬酸脱氢酶的底物特异性，这表明这些酶的底物特异性相对较宽。基于底物特异性，将3-羟基亚烷基-和3-羧基亚烷基-苹果酸酯衍生物设计为均异柠檬酸脱氢酶的特异性抑制剂。合成抑制剂显示出中等的竞争抑制活性，并且（R，在合成的抑制剂中，Z）-3-羧丙基亚甲基丙烯酸酯的抑制作用最大。因此，均异柠檬酸脱氢酶似乎优先识别均异柠檬酸的延伸构象。
• Biological Synthesis of Difunctional Alkanes from Carbohydrate Feedstocks
  申请人：Baynes Brian M.

  公开号：US20110171696A1

  公开（公告）日：2011-07-14

  Aspects of the invention relate to methods for the production of difunctional alkanes in host cells. In particular, aspects of the invention describe components of genes associated with the difunctional alkane production from carbohydrate feedstocks in host cells. More specifically, aspects of the invention describe metabolic pathways for the production of adipic acid, aminocaproic acid, caprolactam, and hexamethylenediamine via 2-ketopimelic acid.

  本发明涉及在宿主细胞中生产双官能基烷烃的方法。具体而言，本发明描述了与从碳水化合物饲料在宿主细胞中生产双官能基烷烃相关的基因组成部分。更具体地，本发明描述了通过2-酮基戊二酸生产己二酸、氨基己酸、己内酰胺和六亚甲基二胺的代谢途径。
• BIOLOGICAL SYNTHESIS OF DIFUNCTIONAL ALKANES FROM CARBOHYDRATE FEEDSTOCKS
  申请人：Baynes Brian M.

  公开号：US20120164702A1

  公开（公告）日：2012-06-28

  Aspects of the invention relate to methods for the production of difunctional alkanes in host cells. In particular, aspects of the invention describe components of genes associated with the difunctional alkane production from carbohydrate feedstocks in host cells. More specifically, aspects of the invention describe metabolic pathways for the production of adipic acid, aminocaproic acid, caprolactam, and hexamethylenediamine via 2-ketopimelic acid.

  本发明涉及在宿主细胞中生产双官能基烷烃的方法。具体而言，本发明描述了与从碳水化合物饲料中在宿主细胞中生产双官能基烷烃相关的基因组成部分。更具体地，本发明描述了通过2-酮基戊二酸生产己二酸、氨基己酸、己内酰胺和六亚甲基二胺的代谢途径。
• Substrate Specificity Determinants of the Methanogen Homoaconitase Enzyme: Structure and Function of the Small Subunit^,
  作者：Jeyaraman Jeyakanthan、Randy M. Drevland、Dasara Raju Gayathri、Devadasan Velmurugan、Akeo Shinkai、Seiki Kuramitsu、Shigeyuki Yokoyama、David E. Graham

  DOI：10.1021/bi901766z

  日期：2010.3.30

  The aconitase family of hydro-lyase enzymes includes three classes of proteins that catalyze the isomerization of alpha-hydroxy acids to beta-hydroxy acids. Besides aconitase, isopropylmalate isomerase (IPMI) proteins specifically catalyze the isomerization of alpha,beta-dicarboxylates with hydrophobic gamma-chain groups, and homoaconitase (HACN) proteins catalyze the isomerization of tricarboxylates with variable chain length gamma-carboxylate groups. These enzymes' stereospecific hydro-lyase activities make them attractive catalysts to produce diastereomers from unsaturated precursors. However, sequence similarity and convergent evolution among these proteins lead to widespread misannotation and uncertainty about gene function. To Find the substrate specificity determinants of homologous IPMI and HACN proteins from Methanocaldococcus jannaschii, the small-subunit HACN protein (MJ1271) was crystallized for X-ray diffraction. The Structural model showed characteristic residues in a flexible loop region between alpha 2 and alpha 3 that distinguish HACN from IPMI and aconitase proteins. Site-directed mutagenesis of MJ1271 produced loop-region variant proteins that were reconstituted with wild-type MJ1003 large-subunit protein. The heteromers formed promiscuous hydro-lyases with reduced activity but broader substrate specificity. Both R26K and R26V variants formed relatively efficient IPMI enzymes, while the T27A variant had uniformly lower specificity constants for both IPMI and HACN substrates. The R26V T27Y variant resembles the MJ1277 IPMI small subunit in its flexible loop sequence but demonstrated the broad substrate specificity of the R26V variant. These mutations may reverse the evolution of HACN activity from an ancestral IPMI gene, demonstrating the evolutionary potential for promiscuity in hydro-lyase enzymes. Understanding these specificity determinants enables the functional reannotation of paralogous HACN and IPMI genes in numerous genome sequences. These structural and kinetic results will help to engineer new stereospecific hydro-lyase enzymes for chemoenzymatic syntheses.