2-酮-6-羟基己酸 | 68469-37-4

• 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
• 中文名称: 2-酮-6-羟基己酸
• 英文名称: 2-keto-6-hydroxyhexanoic acid
• 英文别名: 6-Hydroxy-2-oxohexanoic acid
• CAS: 68469-37-4
• 化学式: C₆H₁₀O₄
• mdl: MFCD19229015
• 分子量: 146.143
• InChiKey: KIKUKXLMZJYPTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-酮-6-羟基己酸 在 L-谷氨酸 、 recombinant Escherichia coli K₁₂ aminotransferase 作用下， 反应 24.0h， 生成 L-6-羟基正亮氨酸
  参考文献：
  名称：

  Asymmetric synthesis ofl-6-hydroxynorleucine from 2-keto-6-hydroxyhexanoic acid using a branched-chain aminotransferase

  摘要：

  L-6-Hydroxynorleucine was synthesized from 2-keto-6-hydroxyhexanoic acid using branched-chain aminotransferase from Escherichia coli with L-glutamate as an amino donor. Since the branched-chain aminotransferase was severely inhibited by 2-ketoglutarate, the branched-chain aminotransferase reaction was coupled with aspartate aminotransferase and pyruvate decarboxylase. Aspartate aminotransferase converted the inhibitory 2-ketoglutarate back to L-glutamate by using L-aspartate as an amino donor. On the other hand, pyruvate decarboxylase further shifted the reaction equilibrium towards L-6-hydroxynorleucine through decarboxylation of pyruvate to acetaldehyde. The concerted action of the three enzymes significantly enhanced the yield compared to that of branched-chain aminotransferase alone. In the coupled reaction, 90.2 mM L-6-hydroxynorleucine (> 99% ee) was produced from 100 mM 2-keto-6-hydroxyhexanoic acid, whereas in a single branched-chain aminotransferase reaction only 22.5 mM L-6-hydroxynorleucine (> 99% ee) was produced.

  DOI：

  10.3109/10242422.2011.638373
• 作为产物：
  描述：

  5-D-羟基丁基海因 在 calcium hydroxide 、 sodium hydroxide 、 beef liver catalase 、 porcine kidney D-amino acid oxidase 作用下， 以 phosphate buffer 、 水 为溶剂， 反应 5.0h， 生成 2-酮-6-羟基己酸
  参考文献：
  名称：

  酶促合成L-6-羟基正亮氨酸。

  摘要：

  L-6-羟基正亮氨酸，一种用于合成血管肽酶抑制剂的关键手性中间体，使用牛肉肝中的谷氨酸脱氢酶，通过2-胺基-6-羟基己酸的还原胺化反应，以89％的收率和> 99％的光学纯度制备。在另一种方法中，将5-（4-羟基丁基）乙内酰脲水解产生的外消旋6-羟基正亮氨酸用D-氨基酸氧化酶处理，以制备含有2-酮基6-羟基己酸和L-6-羟基正亮氨酸的混合物，然后还原胺化步骤将混合物完全转化为L-6-羟基正亮氨酸，产率为91％至97％，光学纯度为> 99％。

  DOI：

  10.1016/s0968-0896(99)00158-3

文献信息

• Paul; Tchelitcheff, Bulletin de la Societe Chimique de France, 1952, p. 808,812
  作者：Paul、Tchelitcheff

  DOI：——

  日期：——
• Biocatalytic synthesis of chiral intermediates for antiviral and antihypertensive drugs
  作者：Ramesh N. Patel

  DOI：10.1007/s11746-999-0139-7

  日期：1999.11

  AbstractThe chiral intermediate (1S,2R) [3‐chloro‐2‐hydroxy‐1‐(phenylmethyl)propyl] carbamic acid, 1,1‐dimethylethyl ester 2a was prepared for the total synthesis of a human immunodeficiency virus protease inhibitor, BMS‐186318. The stereoselective reduction of (1S) [3‐chloro‐2‐oxo‐1(phenylmethyl)propyl] carbamic acid, 1,1‐dimethylethyl ester 1 was carried out using microbial cultures, among which Streptomyces nodosus SC 13149 efficiently reduced 1 to 2a. A reaction yield of 80%, enantiomeric excess (e.e.) of 99.8%, and diastereomeric purity of 99% were obtained for chiral alcohol 2a. Chiral l‐6‐hydroxy norleucine 3, an intermediate in the synthesis of antihypertensive drug, was prepared by reductive amination of 2‐keto‐6‐hydroxyhexanoic acid 4 using beef liver glutamate dehydrogenase. The cofactor NADH required for this reaction was regenerated using glucose dehydrogenase from Bacillus sp. A reaction yield of 80% and e.e. of 99.5% were obtained for l‐6‐hydroxynorleucine 3. To avoid the lengthy chemical synthesis of the ketoacid, a second route was developed in which racemic 6‐hydroxynorleucine [readily available from hydrolysis of 5‐(4‐hydroxybutyl) hydantoin 5] was treated with d‐amino acid oxidase from Trigonopsis variabilis to selectively convert the d‐isomer of racemic 6‐hydroxynorleucine to 2‐keto‐6‐hydroxyhexanoic acid 4 and l‐6‐hydroxynorleucine 3. Subsequently, the 2‐keto‐6‐hydroxyhexanoic acid 4 was converted to l‐6‐hydroxynorleucine by reductive amination using glutamate dehydrogenase. A reaction yield of 98% and an e.e. of 99.5% were obtained.
• FATTY ACID AMIDE HYDROLASE ASSAY
  申请人：Warner-Lambert Company LLC

  公开号：EP1851328A1

  公开（公告）日：2007-11-07
• A HIGH YIELD ROUTE FOR THE PRODUCTION OF COMPOUNDS FROM RENEWABLE SOURCES
  申请人：Zymochem Inc.

  公开号：EP3047030A2

  公开（公告）日：2016-07-27
• PRODUCTION OF CHEMICALS FROM RENEWABLE SOURCES
  申请人：Zymochem, Inc.

  公开号：EP3959328A1

  公开（公告）日：2022-03-02