(2R,3S)-3-methylmalic acid | 152204-30-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R,3S)-3-methylmalic acid
• 英文别名: (2R,3S)-2-hydroxy-3-methylsuccinic acid；(2R,3S)-2-hydroxy-3-methylbutanedioic acid
• CAS: 152204-30-3
• 化学式: C₅H₈O₅
• 分子量: 148.116
• InChiKey: NPYQJIHHTGFBLN-STHAYSLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-methylmalic acid 、 2,2-二甲氧基丙烷 在 无水氯化铜 甲烷 作用下， 以 丙酮 为溶剂， 反应 17.0h， 以gave the title product (mixture of diatereoisomers) as a greenish oil (1.85 g, 59%)的产率得到(2S)-2-[(4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]propanoic acid
  参考文献：
  名称：

  N-HYDROXYAMIDE DERIVATIVES AND USE THEREOF

  摘要：

  本发明涉及公式（I）的N-羟基酰胺衍生物及其在特定领域的应用，尤其是用于治疗和/或预防自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、癌症、呼吸系统疾病和纤维化，包括多发性硬化、关节炎、肺气肿、慢性阻塞性肺疾病、肝和肺纤维化。

  公开号：

  US20110263628A1
• 作为产物：
  描述：

  柠康酸 在 2-环己胺基乙磺酸 、 potassium chloride 、 potassium hydroxide 作用下， 生成 (2R,3S)-3-methylmalic acid
  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

• [EN] N-HYDROXYAMIDE DERIVATIVES AND USE THEREOF<br/>[FR] DERIVES N-HYDROXYAMIDE ET LEUR APPLICATION
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2006010751A1

  公开（公告）日：2006-02-02

  The present invention is related to N-hydroxyamide derivatives of Formula (I) and use thereof, in particular for the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.

  本发明涉及式（I）的N-羟基酰胺衍生物及其用途，特别是用于治疗和/或预防自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、癌症、呼吸道疾病和纤维化，包括多发性硬化症、关节炎、肺气肿、慢性阻塞性肺病、肝脏和肺部纤维化。
• Preparation of both enantiomers of malic and citramalic acid and other hydroxysuccinic acid derivatives by stereospecific hydrations of cis or trans 2-butene-1,4-dioic acids with resting cells of Clostridium formicoaceticum
  作者：Richard Eck、Helmut Simon

  DOI：10.1016/s0040-4020(01)85678-7

  日期：1994.1

  (S)-malic, (R)citramalic, (S)-citramalic, (2R,3S)-2-hydroxy-3-methyl-succinic and (2R,3S)-2,3-dimethyl-2-hydroxysuccinic acid were prepared on scales up to 25 mmol by stereospecific addition of water to different 2-butene-1,4-dioic acid derivatives catalyzed by resting cells of Clostridium formicoaceticum (Scheme 1). The (3R)-monodeuterio (R)- and (S)-malic acid as well as (R)- and (S)-citramalic acid were

  （R）-苹果酸，（S）-苹果酸，（R）柠檬酸，（S）-柠檬酸，（2 R，3 S）-2-羟基-3-甲基-琥珀酸和（2 R，3 S）-2通过将水立体定向加成到不同的2-丁烯-1,4-二酸衍生物中，由梭状梭状芽孢杆菌的静止细胞催化，可制备高达25 mmol的规模的3-3-二甲基-2-羟基琥珀酸（方案1）。的（3 - [R）-monodeuterio（[R ）-和（小号） -苹果酸，以及（- [R ）-和（小号）-citramalic苯甲酸用冷冻干燥的细胞中制备的2H 2 O缓冲区。在大多数情况下，产品的立体化学纯度均≥99％。
• Dalbergia species—VII
  作者：B.J. Donnelly、D.M.X. Donnelly、A.M. O'Sullivan、J.P. Prendergast

  DOI：10.1016/s0040-4020(01)82981-1

  日期：1969.1

  The isolation and structure of (−)-melanoxin a new 2,3-dihydrobenzofuran is described. Spectroscopic methods established structure I for melanoxin and confirmation was obtained by synthesis of O-diethyldehydromelanoxin (II, R = Et). Ozonolysis of (−)-melanoxin yielded (−)-(2S,3R)-3-methylmalic acid (III), whilst hydrogenolysis and subsequent ozonolysis gave (+)-(R)-methyl-succinic acid (IV). These

  描述了一种新的2,3-二氢苯并呋喃（-）-黑素蛋白的分离和结构。光谱法确定了黑色素的结构I，并通过合成O-二乙基脱氢黑色素（II，R = Et）得到了证实。（-）-黑素蛋白的臭氧分解产生（-）-（2 S，3 R）-3-甲基苹果酸（III），而氢解和随后的臭氧分解则得到（+）-（R）-甲基琥珀酸（IV）。这些实验表明（-）-黑素蛋白具有（2 S，3 S）-构型。已知的（S）-4'-羟基-4-甲氧基dalbergione（V）melannein（VI）和2,5-二甲氧基醌也从Dalbergia melanoxylon中分离出来。
• N-Hydroxyamide Derivatives and Use Thereof
  申请人：Swinnen Dominique

  公开号：US20080021028A1

  公开（公告）日：2008-01-24

  The present invention is related to N-hydroxyamide derivatives of Formula (I) and use thereof, in particular for the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.

  本发明涉及公式（I）的N-羟基酰胺衍生物及其用途，特别用于治疗和/或预防自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、癌症、呼吸系统疾病和纤维化，包括多发性硬化症、关节炎、肺气肿、慢性阻塞性肺疾病、肝脏和肺纤维化。
• N-HYDROXYAMIDE DERIVATIVES AND USE THEREOF
  申请人：Swinnen Dominique

  公开号：US20110263628A1

  公开（公告）日：2011-10-27

  The present invention is related to N-hydroxyamide derivatives of Formula (I) and use thereof in particular for the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.

  本发明涉及公式（I）的N-羟基酰胺衍生物及其在特定领域的应用，尤其是用于治疗和/或预防自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、癌症、呼吸系统疾病和纤维化，包括多发性硬化、关节炎、肺气肿、慢性阻塞性肺疾病、肝和肺纤维化。