3,3-dideuterio-2-oxo-pentanedioic acid | 53931-68-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 3,3-dideuterio-2-oxo-pentanedioic acid
• 英文别名: 3,3-dideuterio-2-oxo-glutaric acid；3,3-Dideuterio-2-oxo-glutarsaeure；3,3-dideuterio-2-oxopentanedioic acid
• CAS: 53931-68-3
• 化学式: C₅H₆O₅
• 分子量: 148.084
• InChiKey: KPGXRSRHYNQIFN-DICFDUPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  10.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  91.67
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3,3-dideuterio-2-oxo-pentanedioic acid 在 palladium on activated charcoal 氯化铵-d4 、 水 、 sodium acetate 、 peroxyformic acid 作用下， 以11%的产率得到DL-[2,3,3-2H3]glutamic acid
  参考文献：
  名称：

  Non-fatty acyl polyketide starter in the biosynthesis of vicenistatin, an antitumor macrolactam antibiotic

  摘要：

  A biosynthetic pathway of an antitumor antibiotic vicenistatin was investigated by feeding experiments of [1-C-13] and [1,2-C-13(2)]acetate, [1-C-13]propionate, [2,3,3-H-2(3)]glutamate, and D-[6,6-H-2(2)]glucose. The elongating units of the aglycon of vicenistatin are derived from standard acetate-propionate, whereas the starter unit appears to be derived from a 3-amino-2-methylpropionate equivalent through the glutamate mutase reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00455-9
• 作为产物：
  描述：

  alpha-酮戊二酸 在 吡啶 、 水 作用下， 生成 3,3-dideuterio-2-oxo-pentanedioic acid
  参考文献：
  名称：

  Macrolactam聚酮糖苷糖苷类抗肿瘤药抗生素Vicenistatins的生物合成途径

  摘要：

  抗肿瘤抗生素vicenistatin M的和vicenistatin生物合成研究由饲喂实验进行[1- 13 C] -和[1,2 13 Ç 2 ]乙酸甲酯，[1- 13 C]丙酸酯，DL-2,3， 3- 2 H 3 ]谷氨酸，d- [6,6- 2 H 2 ]葡萄糖，1- [ 15 N]谷氨酸和1- [CH 3 – 13C]蛋氨酸。大内酰胺糖苷配基的延伸单元以标准方式衍生自乙酸酯和丙酸酯，而起始剂单元并非衍生自脂肪酸，而是衍生自3-氨基-2-甲基丙酸酯或其等价物，可能是由谷氨酸突变酶和脱羧酶。糖单元似乎是通过共同中间体的官能团的多种修饰而生物合成的。

  DOI：

  10.1016/s0040-4020(00)00792-4

文献信息

• Enzymatic synthesis of specifically ² H-labelled L-glutamic acids and ² H-, ¹⁵ N-, ¹³ C-labelled L-glutamines on a preparative scale
  作者：A. Ogrel、I. A. Vasilenko、J. Lugtenburg、J. Raap

  DOI：10.1002/recl.19941130706

  日期：——

  conversion of 2-oxoglutaric acid using glutamate dehydrogenase (GDH, E.C. 1.4.1.3.), alcohol dehydrogenase (ADH, E.C. 1.1.1.1.) and (2H6)ethanol. (3,3-2H2)-L-Glutamic acid was prepared by enzymatic conversion of 2-oxo-3,3-di-deuteroglutaric acid which was easily obtained from 2-oxoglutaric acid by an isotope exchange reaction in 2H2O at pH 13.0. (4,4-2H2)-L-Glutamic acid was obtained by chemical exchange

  在本文中，我们以克为单位报告了2 H-标记的L-谷氨酸和2 H-，15 N-，13 C-标记的L-谷氨酰胺的制备方法。获得的产物具有高同位素富集度（> 98％）和高光学纯度。合成方案允许每个H，C和N位置或任何位置组合的特定同位素富集。（2- 2 H）-L-谷氨酸是通过使用谷氨酸脱氢酶（GDH，EC 1.4.1.3。），醇脱氢酶（ADH，EC 1.1.1.1。）和（2 H 6）乙醇。（3,3- 2 ħ 2通过将2-氧代戊二酸在2 H 2 O中于pH 13.0进行同位素交换反应而容易地制得2-氧代-3,3-二-氘代戊二酸来制备）-L-谷氨酸。通过在20％2 HCl中的化学交换获得（4，4- 2 H 2）-L-谷氨酸。L-谷氨酰胺[（2- 2 H）-，（3,3- 2 H 2）-，（4,4- 2 H 2）-和（5- 13 C）-L-Gln]的四种不同的异构体通过使用谷氨酰胺合成酶（GS，EC 6
• In Vitro Biosynthesis of the Nonproteinogenic Amino Acid Methoxyvinylglycine
  作者：Jon B. Patteson、Zachary D. Dunn、Bo Li

  DOI：10.1002/anie.201713419

  日期：2018.6.4

  nonproteinogenic amino acids featuring an essential vinyl ether conferring mechanism‐based inhibition of pyridoxal phosphate enzymes. The gene clusters for a few oxyvinylglycines are known, yet the biosynthetic origin of the vinyl ether is elusive. The in vitro biosynthesis of methoxyvinylglycine or l‐2‐amino‐4‐methoxy‐trans‐3‐butenoic acid (AMB) is reported. It is shown that AMB is made from glutamate as an alanyl‐AMB

  氧乙烯基甘氨酸是一类非蛋白氨基酸，具有必需的乙烯基醚，可基于机理抑制吡ido醛磷酸酶。几种氧乙烯基甘氨酸的基因簇是已知的，但是乙烯基醚的生物合成来源是难以捉摸的。甲氧乙烯基甘氨酸或l -2-氨基-4-甲氧基反式的体外生物合成报道了3-丁烯酸（AMB）。结果表明，AMB是由谷氨酸制成的丙氨酰-AMB二肽，并提供了N-末端Ala的基本原理；使用化学捕获方法，对非核糖体肽合成酶（NRPS）进行修饰的顺序和时机如下：确定了结合的底物，包括Gluβ-碳的隐性羟基化。消除该羟基可能会产生关键的α，β-脱氢氨基酸中间体，从而促进脱羧。这项工作揭示了乙烯基醚的生物合成，并揭示了新的NRPS化学。
• Cyclosporin A-induced free radical generation is not mediated by cytochrome P-450
  作者：Alexandra Krauskopf、Timo M Buetler、Nathalie S D Nguyen、Katherine Macé、Urs T Ruegg

  DOI：10.1038/sj.bjp.0704544

  日期：2002.2

  Reactive oxygen species (ROS) have been proposed to play a role in the side effects of the immunosuppressive drug cyclosporin A (CsA). The aim of this study was to investigate whether cytochrome P‐450 (CYP) dependent metabolism of CsA could be responsible for ROS generation since it has been suggested that CsA may influence the CYP system to produce ROS. We show that CsA (1 – 10 μM) generated antioxidant‐inhibitable ROS in rat aortic smooth muscle cells (RASMC) using the fluorescent probe 2,7‐dichlorofluorescin diacetate. Using cytochrome c as substrate, we show that CsA (10 μM) did not inhibit NADPH cytochrome P‐450 reductase in microsomes prepared from rat liver, kidney or RASMC. CsA (10 μM) did not uncouple the electron flow from NADPH via NADPH cytochrome P‐450 reductase to the CYP enzymes because CsA did not inhibit the metabolism of substrates selective for several CYP enzymes that do not metabolize CsA in rat liver microsomes. CsA (10 μM) did not generate more radicals in CYP 3A4 expressing immortalized human liver epithelial cells (T5‐3A4 cells) than in control cells that do not express CYP 3A4. Neither diphenylene iodonium nor the CYP 3A inhibitor ketoconazole were able to block ROS formation in rat aortic smooth muscle or T5‐3A4 cells. These results demonstrate that CYP enzymes do not contribute to CsA‐induced ROS formation and that CsA neither inhibits NADPH cytochrome P‐450 reductase nor the electron transfer to the CYP enzymes. British Journal of Pharmacology (2002) 135, 977–986; doi:10.1038/sj.bjp.0704544

  活性氧（ROS）被认为在免疫抑制药物环孢素A（CsA）的副作用中发挥一定作用。本研究的目的是探讨CsA是否通过细胞色素P-450（CYP）依赖的代谢途径产生ROS，因为已有研究表明CsA可能影响CYP系统以产生ROS。我们发现，使用荧光探针2,7-二氯荧光素二乙酸酯，CsA（1 – 10 μM）在大鼠胸主动脉平滑肌细胞（RASMC）中产生了抗氧化剂可抑制的ROS。以细胞色素c作为底物，我们发现CsA（10 μM）并未抑制从大鼠肝脏、肾脏或RASMC制备的微粒体中的NADPH细胞色素P-450还原酶的活性。CsA（10 μM）并未阻断通过NADPH途径由NADPH细胞色素P-450还原酶向CYP酶传递的电子流动，因为CsA并未抑制大鼠肝脏微粒体中多个并不代谢CsA的CYP酶底物的代谢。CsA（10 μM）在表达CYP 3A4的永生化人肝上皮细胞（T5-3A4细胞）中产生的自由基并不比不表达CYP 3A4的对照细胞多。无论是二苯基碘鎓还是CYP 3A抑制剂酮康唑，都无法阻断大鼠胸主动脉平滑肌或T5-3A4细胞中的ROS形成。这些结果表明，CYP酶并不参与CsA诱导的ROS生成，且CsA既不抑制NADPH细胞色素P-450还原酶，也不阻碍电子向CYP酶的传递。英国药理学杂志（2002）135，977–986；doi:10.1038/sj.bjp.0704544
• Non-fatty acyl polyketide starter in the biosynthesis of vicenistatin, an antitumor macrolactam antibiotic
  作者：Miyuki Otsuka、Tadashi Eguchi、Kazutoshi Shindo、Katsumi Kakinuma

  DOI：10.1016/s0040-4039(98)00455-9

  日期：1998.5

  A biosynthetic pathway of an antitumor antibiotic vicenistatin was investigated by feeding experiments of [1-C-13] and [1,2-C-13(2)]acetate, [1-C-13]propionate, [2,3,3-H-2(3)]glutamate, and D-[6,6-H-2(2)]glucose. The elongating units of the aglycon of vicenistatin are derived from standard acetate-propionate, whereas the starter unit appears to be derived from a 3-amino-2-methylpropionate equivalent through the glutamate mutase reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Biosynthetic Pathway of Macrolactam Polyketide Glycoside Antitumor Antibiotic Vicenistatins
  作者：Miyuki Otsuka、Masaki Fujita、Yoshitaka Matsushima、Tadashi Eguchi、Kazutoshi Shindo、Katsumi Kakinuma

  DOI：10.1016/s0040-4020(00)00792-4

  日期：2000.10

  The biosynthetic studies of antitumor antibiotic vicenistatin and vicenistatin M were undertaken by feeding experiments with [1-13C]- and [1,2-13C2]acetate, [1-13C]propionate, dl-[2,3,3-2H3]glutamate, d-[6,6-2H2]glucose, l-[15N]glutamate, and l-[CH3–13C]methionine. The elongating units of the macrolactam aglycon were derived from acetate and propionate in a standard manner, whereas the starter unit

  抗肿瘤抗生素vicenistatin M的和vicenistatin生物合成研究由饲喂实验进行[1- 13 C] -和[1,2 13 Ç 2 ]乙酸甲酯，[1- 13 C]丙酸酯，DL-2,3， 3- 2 H 3 ]谷氨酸，d- [6,6- 2 H 2 ]葡萄糖，1- [ 15 N]谷氨酸和1- [CH 3 – 13C]蛋氨酸。大内酰胺糖苷配基的延伸单元以标准方式衍生自乙酸酯和丙酸酯，而起始剂单元并非衍生自脂肪酸，而是衍生自3-氨基-2-甲基丙酸酯或其等价物，可能是由谷氨酸突变酶和脱羧酶。糖单元似乎是通过共同中间体的官能团的多种修饰而生物合成的。