benzyl (2S,4S)-4-hydroxy-6-oxo-2-piperidinecarboxylate | 653589-27-6

• 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: benzyl (2S,4S)-4-hydroxy-6-oxo-2-piperidinecarboxylate
• 英文别名: (2S,4S)-4-hydroxy-6-oxo-piperidine-2-carboxylic acid benzyl ester；benzyl (2S,4S)-4-hydroxy-6-oxopiperidine-2-carboxylate
• CAS: 653589-27-6
• 化学式: C₁₃H₁₅NO₄
• 分子量: 249.266
• InChiKey: FGBLZCOEKYLXDT-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.37
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.63
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  benzyl (2S,4S)-4-hydroxy-6-oxo-2-piperidinecarboxylate 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以87%的产率得到(2S,4S)-4-hydroxy-6-oxo-piperidine-2-carboxylic acid
  参考文献：
  名称：

  为二氢乳清酶的活性位点设计的抑制剂。

  摘要：

  已经合成了四种新的化合物作为大肠杆菌中二氢乳清酶的潜在抑制剂。NMR光谱显示溶液中以水合物（7），烯醇（8）和烯醇盐（9）互变异构体的混合物形式存在4,6-二氧-哌啶-2（S）-羧酸（3）形式。发现该化合物在pH值为7-9时是相对于二氢乳清酸酯和硫代二氢乳清酸酯的竞争性抑制剂。76 microM的K（i）在pH7.0时最低，在此溶液中酮3和水合物形式的抑制剂3占优势。将化合物3还原为两个非对映体4-羟基衍生物（4和5），然后脱水得到烯烃衍生物1,2,3,6-四氢-6-氧吡啶-2-（S）-羧酸（6） 。在pH 8.0时，化合物4-6是硫代二氢乳清酸酯的竞争性抑制剂，K（i）值为3.0、1.6和2.3 mM。

  DOI：

  10.1016/j.bioorg.2005.08.001
• 作为产物：
  描述：

  Boc-L-天冬氨酸 1-苄酯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 82.0h， 生成 benzyl (2S,4S)-4-hydroxy-6-oxo-2-piperidinecarboxylate
  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

• Synthesis of Enantiopure 4-Hydroxypipecolate and 4-Hydroxylysine Derivatives from a Common 4,6-Dioxopiperidinecarboxylate Precursor
  作者：J. Marin、C. Didierjean、A. Aubry、J.-R. Casimir、J.-P. Briand、G. Guichard

  DOI：10.1021/jo0353886

  日期：2004.1.1

  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).
• Inhibitors designed for the active site of dihydroorotase
  作者：Yingchun Li、Frank M. Raushel

  DOI：10.1016/j.bioorg.2005.08.001

  日期：2005.12

  where the ketone and hydrate forms of the inhibitor 3 predominate in solution. Compound 3 was reduced to the two diastereomeric 4-hydroxy derivatives (4 and 5) and then dehydrated to yield the alkene derivative, 1,2,3,6-tetrahydro-6-oxopyridine-2(S)-carboxylic acid (6). Compounds 4-6 were competitive inhibitors versus thio-dihydroorotate at pH 8.0 with K(i) values of 3.0, 1.6, and 2.3 mM. Dihydroorotase

  已经合成了四种新的化合物作为大肠杆菌中二氢乳清酶的潜在抑制剂。NMR光谱显示溶液中以水合物（7），烯醇（8）和烯醇盐（9）互变异构体的混合物形式存在4,6-二氧-哌啶-2（S）-羧酸（3）形式。发现该化合物在pH值为7-9时是相对于二氢乳清酸酯和硫代二氢乳清酸酯的竞争性抑制剂。76 microM的K（i）在pH7.0时最低，在此溶液中酮3和水合物形式的抑制剂3占优势。将化合物3还原为两个非对映体4-羟基衍生物（4和5），然后脱水得到烯烃衍生物1,2,3,6-四氢-6-氧吡啶-2-（S）-羧酸（6） 。在pH 8.0时，化合物4-6是硫代二氢乳清酸酯的竞争性抑制剂，K（i）值为3.0、1.6和2.3 mM。