di(tert-butyl) (2S)-4,6-dioxo-1,2-piperidinedicarboxylate | 653589-10-7

• 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: di(tert-butyl) (2S)-4,6-dioxo-1,2-piperidinedicarboxylate
• 英文别名: 1,2-di-tert-butyl (2S)-4,6-dioxopiperidine-1,2-dicarboxylate；Di-tert-butyl (2S)-4,6-dioxopiperidine-1,2-dicarboxylate；ditert-butyl (2S)-4,6-dioxopiperidine-1,2-dicarboxylate
• CAS: 653589-10-7
• 化学式: C₁₅H₂₃NO₆
• 分子量: 313.351
• InChiKey: YOYFZEQSJGFFCL-JTQLQIEISA-N

物化性质

• 熔点：
  114-116 °C
• 沸点：
  446.8±45.0 °C(Predicted)
• 密度：
  1.183±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  90
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di(tert-butyl) (2S)-4,6-dioxo-1,2-piperidinedicarboxylate 在 dimethyl sulfide borane 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 di(tert-butyl) (2S,4R)-4-hydroxy-1,2-piperidinedicarboxylate
  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
• 作为产物：
  描述：

  2-tert-butoxycarbonylamino-4-(2,2-dimethyl-4,6-dioxo[1,3]dioxan-5-yl)-4-oxobutyric acid tert-butyl ester 以 乙酸乙酯 为溶剂， 反应 3.0h， 以12.61 g的产率得到di(tert-butyl) (2S)-4,6-dioxo-1,2-piperidinedicarboxylate
  参考文献：
  名称：

  SYNTHESIS OF ENANTIOPURE DI(TERT-BUTYL) (2S,4S)-4-HYDROXY-6-OXO-1,2-PIPERIDINEDICARBOXYLATE. A USEFUL BUILDING BLOCK FOR THE PREPARATION OF 4-HYDROXYPIPECOLATE DERIVATIVES

  摘要：

  DOI：

  10.15227/orgsyn.085.0147

文献信息

• [EN] ARYL HETEROBICYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ARYLÉS EN TANT QUE BLOQUEURS DU CANAL POTASSIQUE SHAKER KV1.3
  申请人：DE SHAW RES LLC

  公开号：WO2021071832A1

  公开（公告）日：2021-04-15

  A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.

  描述了化合物式(I)或其药用可接受的盐，其中取代基如本文所定义。还描述了包括该化合物的药物组合物以及使用该化合物的方法。
• Diastereoselective Synthesis of Functionally Diverse Substituted Pipecolic ­Acids
  作者：Stephen Hanessian、Ludivine Riber、Julien Marin

  DOI：10.1055/s-0028-1087477

  日期：——

  The synthesis of CIS-4-substitutedpipecolic acids, 4,5-disubstituted pipecolic acids, and their 6-oxoanalogues starting from enantiopure L-asparticacid is reported. The synthetic strategy involves as key steps,Suzuki-Miyaura and related Pd-mediated couplings, followedby a catalytic hydrogenation with excellent yields and diastereoselectivities.Enolate alkylations provide 4,5- TRANS-orientedfunctionalization

  报道了从对映体纯 L-天冬氨酸开始合成 CIS-4-取代哌啶酸、4,5-二取代哌啶酸和它们的 6-氧代类似物。合成策略包括作为关键步骤的 Suzuki-Miyaura 和相关的 Pd 介导的偶联，然后是具有优异产率和非对映选择性的催化氢化。烯醇烷基化提供 4,5-反式定向功能化。
• [EN] ARYL HETEROBICYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS<br/>[FR] COMPOSÉS ARYLE HÉTÉROBICYCLIQUES EN TANT QUE BLOQUEURS DES CANAUX POTASSIQUES SHAKER KV1.3
  申请人：DE SHAW RES LLC

  公开号：WO2021071803A1

  公开（公告）日：2021-04-15

  A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.

  描述了化合物的化学式（I）或其药学上可接受的盐，其中取代基如本文所定义。还描述了包括该化合物的药物组合物以及使用该化合物的方法。
• 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。
• 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).