(2R,4S)-4-hydroxypiperidine-2-carboxylic acid hydrochloride | 143616-97-1

• 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: (2R,4S)-4-hydroxypiperidine-2-carboxylic acid hydrochloride
• 英文别名: 4-hydroxypiperidine-2-carboxylic acid hydrochloride；cis-(2R,4S)-4-hydroxypipecolic acid hydrochloride；(2R,4S)-4-hydroxypiperidine-2-carboxylic acid;hydrochloride
• CAS: 143616-97-1
• 化学式: C₆H₁₁NO₃*ClH
• 分子量: 181.619
• InChiKey: ZRVKITWJAUZNSB-UYXJWNHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.39
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  69.6
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,4S)-4-hydroxypiperidine-2-carboxylic acid hydrochloride 在 palladium on activated charcoal 氢气 、 caesium carbonate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,5S)-2-[4-(4-Fluoro-benzyloxy)-benzenesulfonyl]-6-oxa-2-aza-bicyclo[3.2.1]octan-7-one
  参考文献：
  名称：

  Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors

  摘要：

  A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme, Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with > 100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00183-x
• 作为产物：
  描述：

  (1R,5S)-2-((R)-1-phenylethyl)-6-oxa-2-azabicyclo[3.2.1]octan-7-one 在 palladium on activated charcoal 氢气 、 盐酸 作用下， 以 甲醇 为溶剂， 生成 (2R,4S)-4-hydroxypiperidine-2-carboxylic acid hydrochloride
  参考文献：
  名称：

  Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors

  摘要：

  A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme, Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with > 100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00183-x

文献信息

• Enantiodivergent Chemoenzymatic Synthesis of 4-Hydroxypiperidine Alkaloids
  作者：Laura Bartali、Andrea Casini、Antonio Guarna、Ernesto G. Occhiato、Dina Scarpi

  DOI：10.1002/ejoc.201000837

  日期：2010.10

  94 % ee, respectively. The S alcohol is then converted into L-fagomine by a stereoselective hydroboration/oxidation as key steps and the cis-(2R,4S)-4-hydroxypipecolic acid by stereoselective hydrogenation. The corresponding D-fagomine and cis-(2S,4R)-4-hydroxypipecolic acid, as well as trans-(2R,4R)-4-hydroxypipecolic acid can be prepared by the same strategy after hydrolysis of the R ester obtained

  报道了一种有效的化学酶合成法戈明对映体以及顺式和反式-4-羟基哌啶酸的对映体。该合成从商业 δ-戊内酰胺开始，在相应的磷酸乙烯酯的 Pd 催化甲氧基羰基化后，进行烯丙基氧化，得到外消旋 4-羟基四氢吡啶衍生物，总产率为 57%。使用来自南极念珠菌 (Novozym 435) 和洋葱伯克霍尔德菌 (脂肪酶 PS Amano IM) 的固定化脂肪酶，通过酶催化酯化来拆分该产物。后者分别提供 95% 和 94% ee 的相应 R 酯和 S 醇。然后通过立体选择性硼氢化/氧化将 S 醇转化为 L-fagomine 作为关键步骤，并通过立体选择性氢化转化为顺式-(2R,4S)-4-羟基哌啶酸。
• Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors
  作者：Michael A. Letavic、Matt Z. Axt、John T. Barberia、Thomas J. Carty、Dennis E. Danley、Kieran F. Geoghegan、Nadia S. Halim、Lise R. Hoth、Ajith V. Kamath、Ellen R. Laird、Lori L. Lopresti-Morrow、Kim F. McClure、Peter G. Mitchell、Vijayalakshmi Natarajan、Mark C. Noe、Jayvardhan Pandit、Lisa Reeves、Gayle K. Schulte、Sheri L. Snow、Francis J. Sweeney、Douglas H. Tan、Chul H. Yu

  DOI：10.1016/s0960-894x(02)00183-x

  日期：2002.5

  A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme, Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with > 100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood. (C) 2002 Elsevier Science Ltd. All rights reserved.