(1R,2S)-1-羟基丙烷-1,2,3-三羧酸 | 6061-97-8

• 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 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (1R,2S)-1-羟基丙烷-1,2,3-三羧酸
• 英文名称: threo-D-isocitric acid
• 英文别名: isocitric acid；D-threo-isocitric acid；(1R,2S)-1-hydroxypropane-1,2,3-tricarboxylic acid
• CAS: 6061-97-8
• 化学式: C₆H₈O₇
• 分子量: 192.125
• InChiKey: ODBLHEXUDAPZAU-ZAFYKAAXSA-N

物化性质

• 沸点：
  329.6±42.0 °C(Predicted)
• 密度：
  1.751±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  7

制备方法与用途

用途

异柠檬酸是一种质子化的异柠檬酸盐，在三羧酸循环中扮演重要角色。它经常被用作检测水果产品（尤其是柑橘类果汁）的真伪及品质的一个指标。

反应信息

• 作为反应物：
  描述：

  (1R,2S)-1-羟基丙烷-1,2,3-三羧酸 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 alpha-酮戊二酸
  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：

  顺式-乌头酸 在 反式-乌头酸 、 2-环己胺基乙磺酸 、 potassium chloride 、 potassium hydroxide 作用下， 生成 (1R,2S)-1-羟基丙烷-1,2,3-三羧酸
  参考文献：
  名称：

  Substrate Specificity Determinants of the Methanogen Homoaconitase Enzyme: Structure and Function of the Small Subunit^,

  摘要：

  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.

  DOI：

  10.1021/bi901766z

文献信息

• Practical Synthesis of the Bicyclic Darunavir Side Chain: (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol from Monopotassium Isocitrate
  作者：Gary L. Moore、Rodger W. Stringham、David S. Teager、Tai-Yuen Yue

  DOI：10.1021/acs.oprd.6b00377

  日期：2017.1.20

  A practical synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol—a key intermediate in the synthesis of darunavir—from monopotassium isocitrate is described. The isocitric acid salt, obtained from a high-yielding fermentation fed by sunflower oil, was converted in several steps to a tertiary amide. This amide, along with the compound’s ester functionalities, was reduced with lithium aluminum hydride

  描述了从异柠檬酸单钾实际合成（3 R，3a S，6a R）-六氢呋喃[2,3 - b ]呋喃-3-醇-darunavir合成的关键中间体。从葵花籽油进料的高产发酵中获得的异柠檬酸盐经数步转化为叔酰胺。该酰胺以及该化合物的酯官能团，用氢化铝锂还原，经酸性处理后得到瞬态氨基三醇。这是原位转换的标题化合物中，地那那韦的双环缩醛呋喃醇侧链是一种用于治疗HIV / AIDS的蛋白酶抑制剂。该方法成功的关键是确定一种最佳的酰胺，该酰胺可以完成反应并成功分离出产物。N-甲基苯胺酰胺被认为是最合适的底物，用于还原和随后环化为所需产物。因此，侧链由异柠檬酸单钾以55％的总产率产生。
• Enzyme-catalyzed organic synthesis: NAD(P)H cofactor regeneration by using glucose-6-phosphate and the glucose-5-phosphate dehydrogenase from Leuconostoc mesenteroides
  作者：Chi-Huey Wong、George M. Whitesides

  DOI：10.1021/ja00406a037

  日期：1981.8

  system based on dehy-drogenation of glucose 6-phosphate (G-6-P) catalyzed by glucose -6-phosphate dehydrogenase (G-6-PDH, G-6-P, NAD(P) oxidoreductase, EC LI.I.49, from Leuconostoc mesenteroides\. The G-6-P required can be prepared by several procedures. The most convenient for syntheses carried out on a-1 mol scale is the hexokinase-catalyzed phosphorylation of glucose with ATP, with coupled acetate kinase

  6-磷酸葡萄糖脱氢酶（来自肠系膜明串珠菌）和葡萄糖 6-磷酸构成了一个有用的系统，用于还原还原型烟酰胺辅因子的再生，用于酶催化的有机合成。该酶在减少 NAD 和 NADP 方面的活性大致相同。[t 是可商购的、便宜的、稳定的且易于固定。葡萄糖 6-磷酸可以通过己糖激酶催化的 ATP 磷酸化葡萄糖（与 ATP 再生相结合）或通过其他方法大量制备。该再生系统的操作通过对映体富集的邻乳酸（0.4 mol，对映体过量95%）和（S）-苄基-a-dl醇（0.4 mol，对映体过量95%）的合成以及苏式-o的合成来说明， (*)-异柠檬酸(0.17mol)。已经探讨了影响溶液中NAD(P)(H)稳定性的因素。需要减少烟酰胺辅因子 (NADH、NADPH) 的酶催化反应并未广泛用于制备化学。2'3 虽然这些反应中有许多在合成中具有潜在价值，但所需的辅因子价格昂贵且在溶液中非常不稳定，并且可以仅在小规模化
• METHODS AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF HEXAHYDROFURO [2,3-B]FURAN-3-OL
  申请人：Chen Weiping

  公开号：US20100168422A1

  公开（公告）日：2010-07-01

  Provided herein are compounds and methods useful for preparing hexahydrofuro[2,3-b]furan-3-ol. Hexahydrofuro[2,3-b]furan-3-ol can be efficiently synthesized in four steps from readily available starting materials.

  本文提供了用于制备六氢呋喃[2,3-b]呋喃-3-醇的化合物和方法。六氢呋喃[2,3-b]呋喃-3-醇可以从易得的起始物质中经过四个步骤高效地合成。
• [EN] METHODS AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF HEXAHYDROFURO[2,3-B]FURAN-3-OL<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES UTILES DANS LA SYNTHÈSE D'HEXAHYDROFURO[2,3-B]FURAN-3-OL
  申请人：OXYRANE UK LTD

  公开号：WO2010075887A1

  公开（公告）日：2010-07-08

  Provided herein are compounds and methods useful for preparing hexahydrofuro[2,3-b]furan-3-ol. Hexahydrofuro[2,3-b]furan-3-ol can be efficiently synthesized in four steps from readily available starting materials.

  本文提供了一些化合物和方法，用于制备六氢呋喃[2,3-b]呋喃-3-醇。该化合物可以通过四个步骤高效地从易得的起始物质合成。
• Studies on Diastereoisomeric α-Amino Acids and Corresponding α-Hydroxy Acids. VII. Influence of β-Configuration on Enzymic Susceptibility
  作者：Milton Winitz、Leah Bloch-Frankenthal、Nobuo Izumiya、Sanford M. Birnbaum、Carl G. Baker、Jesse P. Greenstein

  DOI：10.1021/ja01592a022

  日期：1956.6