methyl cis-4-hydroxy-3-piperidinecarboxylate | 83563-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl cis-4-hydroxy-3-piperidinecarboxylate
• 英文别名: methyl (3S,4R)-4-hydroxypiperidine-3-carboxylate
• CAS: 83563-72-8
• 化学式: C₇H₁₃NO₃
• 分子量: 159.185
• InChiKey: KQOGWNKGUKQZHP-NTSWFWBYSA-N

物化性质

• 沸点：
  257.2±40.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-溴-1-苯基丁-1-烯基)苯 、 methyl cis-4-hydroxy-3-piperidinecarboxylate 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以46%的产率得到methyl N-(4,4-diphenyl-3-butenyl)-cis-4-hydroxy-3-piperidinecarboxylate
  参考文献：
  名称：

  Orally Active and Potent Inhibitors of γ-Aminobutyric Acid Uptake

  摘要：

  3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].

  DOI：

  10.1021/jm50001a020
• 作为产物：
  描述：

  盐酸-4-哌啶酮-3-羧酸乙酯 在 sodium carbonate 、 烯丙醇 、 三氟乙酸 、 蔗糖 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 26.25h， 生成 methyl cis-4-hydroxy-3-piperidinecarboxylate
  参考文献：
  名称：

  A Study of Baker's Yeast Reduction of Piperidone-carboxylates.

  摘要：

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.

  DOI：

  10.3891/acta.chem.scand.52-0461

文献信息

• N-substituted azaheterocyclic carboxylic acids and their esters
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0066456A1

  公开（公告）日：1982-12-08

  -Substituted azaheterocyclic carboxylic acids and their esters, of the formula:- wherein: n is a positive whole integer 2, 3 or 4; m is zero; R4 is hydrogen, or lower alkyl of from 1 to 4 carbon atoms; the dotted line represents an optional bond; R5 is hydrogen, or hydroxy, or when the dotted line forms a double bond, hydrogen; B is wherein R, is hydrogen, fluorine, chlorine, methyl or methoxy; Y is -C(A)=C(R3)- -CH -CHR3- in which case n is 3 or 4, or -C=C-, wherein R2 is hydrogen, fluorine, chlorine, methyl or methoxy, R3 is hydrogen or methyl, and A is 2-thienyl, 3-thienyl or cyclohexyl; or B-Y is (cyclohexyl)2C=C(R3)-; or when Y is a -C(A)=C(R3)- m may also be one: or a pharmaceutically acceptable acid addition salt thereof, useful as inhibitors of GABA uptake, are prepared by reacting an appropriate N-alkylating derivative with an ester of an N-unsubstituted azaheterocyclic carboxylic acid followed by hydrolysis of the ester.

  -式中的取代杂杂环羧酸及其酯类 其中 n 为正整数 2、3 或 4； m 为零； R4 是氢或 1 至 4 个碳原子的低级烷基； 虚线代表任选键； R5 是氢、或羟基、或当虚线形成双键时是氢； B 是 其中 R 是氢、氟、氯、甲基或甲氧基； Y 是-C(A)=C(R3)--CH -其中 R2 是氢、氟、氯、甲基或甲氧基，R3 是氢或甲基，而 A 是 2-噻吩基、3-噻吩基或环己基； 或 B-Y 是 (环己基)2C=C(R3)-； 或当 Y 是-C(A)=C(R3)-时，m 也可以是一个：或其药学上可接受的酸加成盐，可作为 GABA 吸收抑制剂，通过将适当的 N-烷基化衍生物与 N-未取代杂杂环羧酸的酯反应，然后水解该酯制备。
• US4383999A
  申请人：——

  公开号：US4383999A

  公开（公告）日：1983-05-17
• Orally Active and Potent Inhibitors of γ-Aminobutyric Acid Uptake
  作者：Fadia E. Ali、William E. Bondinell、Penelope A. Dandridge、James S. Frazee、Eleanor Garvey、Gerald R. Girard、Carl Kaiser、Thomas W. Ku、John J. Lafferty、George I. Moonsammy、Hye-Ja Oh、Julia A. Rush、Paulette E. Setler、Orum D. Stringer、Joseph W. Venslavsky、Beth W. Volpe、Libby M. Yunger、Charles L. Zirkle

  DOI：10.1021/jm50001a020

  日期：1985.5

  3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].
• A Study of Baker's Yeast Reduction of Piperidone-carboxylates.
  作者：Marianne Willert、Mikael Bols、Anders Hjelholt Pedersen、Palle Schneider、Louisa Barré、Ole Hammerich、Inger Søtofte、Bengt Långström

  DOI：10.3891/acta.chem.scand.52-0461

  日期：——

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.