(2S,4S)-4-羟基-2-哌啶羧酸 | 4382-31-4

• 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: (2S,4S)-4-羟基-2-哌啶羧酸
• 中文别名: 6H-噁唑并[3,4:1,2]吡咯并[3,4-d]-1,2,3-三唑(9CI)
• 英文名称: trans-4-hydroxypipecolic acid
• 英文别名: (2S,4S)-4-hydroxypiperidin-1-ium-2-carboxylate
• CAS: 4382-31-4
• 化学式: C₆H₁₁NO₃
• 分子量: 145.158
• InChiKey: KRHNXNZBLHHEIU-WHFBIAKZSA-N

物化性质

• 沸点：
  346.0±42.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  10
• 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：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4S)-4-羟基-2-哌啶羧酸 在 barium dihydroxide 作用下， 以 水 为溶剂， 反应 12.0h， 生成 (2S,4r)-顺式-4-羟基哌啶-2-羧酸
  参考文献：
  名称：

  来自 Calliandra 的 Cis-4-hydroxypipecolic acid 和 2,4-cis-4,5-trans-4,5-dihydroxypipecolic acid

  摘要：

  摘要 从Calliandra pittieri的叶子中分离得到顺式-4-羟基哌啶酸和2,4-顺式-4,5-反式-4,5-二羟基哌啶酸。描述了一种用于解析从 Calliandra 中分离出的八种亚氨基酸的系统。

  DOI：

  10.1016/0031-9422(83)80098-3
• 作为产物：
  描述：

  di(tert-butyl) (2S,4R)-4-hydroxy-1,2-piperidinedicarboxylate 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 2.5h， 生成 (2S,4S)-4-羟基-2-哌啶羧酸
  参考文献：
  名称：

  Synthesis of Enantiopure 4-Hydroxypipecolate and 4-Hydroxylysine Derivatives from a Common 4,6-Dioxopiperidinecarboxylate Precursor

  摘要：

  tert-Butyl 2-substituted 4,6-dioxo-1-piperidinecarboxylates 4 have been prepared in good yield starting from Boc-Asp-(OBu)-Bu-t and other beta-amino acids. By analogy with chiral tetramic acids, their reduction by NaBH4 in CH2Cl2/AcOH afforded the corresponding cis-4-hydroxy delta-lactams in good yield and stereoselectivity (68-98% de). In the absence of the A(1,3) strain (reduction of 6-substituted 2,4-dioxo-1-piperidines 7), the cis-4-hydroxy isomer was still obtained as the major product but the de values were consistently lower. 4-Hydroxy-6-oxo-1,2-piperidinedicarboxylate 2a, readily accessible from Boc-Asp-OtBu (three steps, 63% overall yield), has proven to be an excellent building block for the synthesis of cis- and trans-4-hydroxypipecolates 17 and 24 (52 and 36% overall yield, respectively) and for the synthesis of a protected 4-hydroxylysine derivative 29 (41% overall yield).

  DOI：

  10.1021/jo0353886

文献信息

• [EN] CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE LA CÉRAMIDE GALACTOSYLTRANSFÉRASE POUR LE TRAITEMENT DE MALADIES
  申请人：BIOMARIN PHARM INC

  公开号：WO2019104011A1

  公开（公告）日：2019-05-31

  Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.

  本发明涉及化合物、制造此类化合物的方法、包含此类化合物的药物组合物和药剂，以及使用此类化合物治疗或预防与鞘氨醇半乳糖基转移酶（CGT）相关疾病或失调的方法，例如，例如，溶酶体贮积病。溶酶体贮积病的例子包括，例如，克拉伯病和异染性脑白质营养不良。
• Use of hydrolases for the synthesis of cyclic amino acids
  作者：Richard C Lloyd、Michael C Lloyd、Mark E.B Smith、Karen E Holt、Jonathan P Swift、Philip A Keene、Stephen J.C Taylor、Raymond McCague

  DOI：10.1016/j.tet.2003.10.116

  日期：2004.1

  The synthesis of several cyclic amino acids that have all the necessary structural features to make them ideal scaffolds for use in medicinal chemistry is described. A key step in each synthesis is the use of hydrolase enzymes to define a chiral centre. In order to elaborate these building blocks into more complex molecules, crystallization and asymmetric hydrogenation were used to define further stereocentres

  描述了具有所有必要结构特征以使其成为用于药物化学的理想支架的几种环状氨基酸的合成。每个合成过程中的关键步骤是使用水解酶来定义手性中心。为了将这些结构单元详细化为更复杂的分子，使用了结晶和不对称氢化来定义进一步的立体中心。
• [EN] CYTOTOXIC AGENTS<br/>[FR] AGENTS CYTOTOXIQUES
  申请人：FEMTOGENIX LTD

  公开号：WO2019043417A1

  公开（公告）日：2019-03-07

  The invention relates to a compound of formula (I) or formula (II) or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; which are useful as medicaments, in particular as anti-proliferative agents and for use as a drug in an antibody-drug conjugate and in the treatment of proliferative diseases.

  该发明涉及公式（I）或公式（II）的化合物，或其药学上可接受的盐、溶剂合物、互变异构体、立体异构体或其混合物；这些化合物可用作药物，特别是作为抗增殖剂，并用作抗体-药物结合物中的药物，用于治疗增殖性疾病。
• Asymmetric Synthesis of the Four Stereoisomers of 4-Hydroxypipecolic Acid
  作者：Franklin A. Davis、Tianan Fang、Bin Chao、David M. Burns

  DOI：10.1055/s-2000-8710

  日期：——

  The asymmetric synthesis of all four stereoisomers of 4-hydroxypipecolic acid (1) from the polyfunctionalized chiral building blocks δ-amino β-keto esters (S S, R)-(+)-5 or (R s, S)-(-)-5 is described. Key steps in the synthesis are the stereoselective reductions of b-phenylpiperidine-2,4-dione (6) and N-sulfinyl δ-amino β-keto esters 5 to cis-4-hydroxy 2-piperidinone 7 and syn-δ-amino β-hydroxy ester 9, respectively. The only protecting/deprotecting group chemistry required is related to the oxidation step.

  描述了从多功能手性构建块 δ-氨基 β-酮酯 (S S, R)-(+)-5 或 (R s, S)-(-)-5 不对称合成4-羟基皮克酸 (1) 的四种立体异构体。合成的关键步骤是对 β-苯基哌啶-2,4-二酮 (6) 和 N-亚砜基 δ-氨基 β-酮酯 5 的立体选择性还原，分别得到顺式的4-羟基-2-哌啶酮 7 和 syn-δ-氨基 β-羟基酯 9。所需的唯一保护/去保护基团化学与氧化步骤有关。
• [EN] AN ENANTIOSELECTIVE PROCESS FOR THE SYNTHESIS OF (2S,4R)-4-HYDROXYPIPECOLIC ACID<br/>[FR] PROCÉDÉ ÉNANTIOSÉLECTIF DE SYNTHÈSE D'ACIDE (2S,4R)-4-HYDROXYPIPÉCOLIQUE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2016120890A1

  公开（公告）日：2016-08-04

  The present invention relates to an improved process for synthesis of 4-hydroxy pipecolic acid. The present invention relates to an improved enantioselective process for the synthesis of (2S,4R)-4-hydroxypipecolic acid via Co(III) (salen)-catalyzed two stereocentered Hydrolytic Kinetic Resolution (HKR) of racemic 1,3-azido epoxide with good yields and high optical purity without any protecting groups. 10 31

  本发明涉及一种改进的合成4-羟基吡哆酸的方法。本发明涉及一种改进的不对称选择性过程，用于通过Co(III) (salen)催化的两个立体中心水解动力学分辨（HKR）合成(2S,4R)-4-羟基吡哆酸，具有良好的产率和高光学纯度，且无需任何保护基团。