(2R,4S)-4-hydroxypipecolic acid methyl ester | 475504-31-5

• 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-hydroxypipecolic acid methyl ester
• 英文别名: 1-Benzyl 2-methyl (2R,4S)-4-hydroxypiperidine-1,2-dicarboxylate；1-O-benzyl 2-O-methyl (2R,4S)-4-hydroxypiperidine-1,2-dicarboxylate
• CAS: 475504-31-5
• 化学式: C₁₅H₁₉NO₅
• 分子量: 293.32
• InChiKey: UZYUNWAMEQIRQH-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4S)-4-hydroxypipecolic acid methyl ester 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 反应 1.0h， 生成 (2R,4R)-4-hydroxypipecolic acid methyl ester
  参考文献：
  名称：

  Novel constrained CCK-B dipeptoid antagonists derived from pipecolic acid

  摘要：

  A new series of 4-substituted pipecolic acid derivatives was prepared and incorporated into dipeptoids. The resulting products behave as moderately potent CCK-B antagonists but their constrained structure and its comparison with structurally related compounds yield valuable information about the conformational requirements for optimal recognition of the CCK-B receptor by antagonists. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00231-5
• 作为产物：
  描述：

  (2R)-4-formylpipecolic acid methyl ester 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以43%的产率得到(2R,4S)-4-hydroxypipecolic acid methyl ester
  参考文献：
  名称：

  Chemoenzymatic Synthesis of the Four Diastereoisomers of 4-Hydroxypipecolic Acid from N-Acetyl-(R,S)-allylglycine:  Chiral Scaffolds for Drug Discovery

  摘要：

  All four diastereoisomers of 4-hydroxypipecolic acid were prepared in a form conveniently protected for drug discovery applications with the use of industrially scaleable methodology. Resolution of the racemic starting material using proprietary acylases followed by an acyliminium ion cyclisation gave diastereomeric mixtures of 4-formyloxypipecolic acid, which were differentiated using an enzyme-catalysed hydrolysis. The products were separated, by partition, and by following a sequence of straightforward chemical steps, the individual stereoisomers of the protected 4-hydroxypipecolates were crystallized to optical purity in 100 g quantities.

  DOI：

  10.1021/op020017x

文献信息

• 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。
• SUBSTITUTED THIAZOLIDINEDIONE INDAZOLES, INDOLES AND BENZOTRIAZOLES AS ESTROGEN-RELATED RECEPTOR-a MODULATORS
  申请人：Bignan Gilles

  公开号：US20110294780A1

  公开（公告）日：2011-12-01

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

  本发明涉及式(I)的化合物，制备这些化合物的方法，组合物，中间体及其衍生物，并用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿关节炎，感染性关节炎，儿童关节炎，银屑病性关节炎，反应性关节炎），与骨相关的疾病（包括与骨形成有关的疾病），乳腺癌（包括对抗雌激素治疗无效的癌症），心血管疾病，软骨相关疾病（如软骨损伤/丧失，软骨退化以及与软骨形成有关的疾病），软骨发育不良，软骨肉瘤，慢性腰部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺疾病，糖尿病，能量稳态紊乱，痛风，假性痛风，脂质紊乱，代谢综合征，多发性骨髓瘤，肥胖，骨关节炎，遗传性骨发育不全，骨溶解性骨转移，软骨软化症，骨质疏松症，帕金森病，牙周病，多肌痛风，Reiter综合征，重复性应激损伤，高血糖，血糖水平升高和胰岛素抵抗等病症的方法。
• An Efficient synthesis of orthogonally protected<i>trans</i>- and<i>cis</i>-4-aminopipecolic acid
  作者：István Szatmári、Loránd Kiss、Ferenc Fülöp

  DOI：10.1002/jhet.5570430539

  日期：2006.9

  A straightforward synthesis of orthogonally Nα/Nγ-protected trans- and cis-4-aminopipecolic acid is reported, starting from methyl cis-4-hydroxypiperidine-2-carboxylate. The two diastereomers were synthesized with the aid of C-4 inversion (the trans isomer) or double C-4 inversion (the cis isomer).

  正交的一种直接合成Ñ α / Ñ γ -保护的反式-和顺式-4- aminopipecolic酸报道，从甲基开始顺-4-羟基哌啶-2-羧酸乙酯。借助于C-4转化（反式异构体）或双C-4转化（顺式异构体）合成两种非对映异构体。
• Synthesis of cis-4-(phosphonooxy)-2-piperidinecarboxylic acid, an N-methyl-D-aspartate antagonist
  作者：Sheryl J. Hays、Thomas C. Malone、Graham Johnson

  DOI：10.1021/jo00012a061

  日期：1991.6
• US8796256B2
  申请人：——

  公开号：US8796256B2

  公开（公告）日：2014-08-05