di(tert-butyl) (2S)-6-oxo-3,6-dihydro-1,2(2H)-pyridinedicarboxylate | 515146-25-5

• 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: di(tert-butyl) (2S)-6-oxo-3,6-dihydro-1,2(2H)-pyridinedicarboxylate
• 英文别名: tert-butyl (2S)-N-tert-butoxycarbonyl-3,6-dihydro-6-oxopyridine-2-carboxylate；ditert-butyl (2S)-6-oxo-2,3-dihydropyridine-1,2-dicarboxylate
• CAS: 515146-25-5
• 化学式: C₁₅H₂₃NO₅
• 分子量: 297.351
• InChiKey: DWYCUYKGALLRPI-JTQLQIEISA-N

物化性质

• 熔点：
  47-49 °C
• 沸点：
  361.3±52.0 °C(Predicted)
• 密度：
  1.136±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  di(tert-butyl) (2S)-6-oxo-3,6-dihydro-1,2(2H)-pyridinedicarboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以94%的产率得到(S)-1,2,3,6-tetrahydro-6-oxopyridine-2(S)-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：

  N-叔丁氧羰基-L-天冬氨酸 1-叔丁酯 在 4-二甲氨基吡啶 、 偶氮二甲酸二异丙酯 、 sodium cyanoborohydride 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三苯基膦 、 对硝基苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 80.0h， 生成 di(tert-butyl) (2S)-6-oxo-3,6-dihydro-1,2(2H)-pyridinedicarboxylate
  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

• Stereodivergent Nitrocyclopropane Formation during Biosynthesis of Belactosins and Hormaomycins
  作者：Shotaro Shimo、Richiro Ushimaru、Alicia Engelbrecht、Mei Harada、Kazunori Miyamoto、Andreas Kulik、Masanobu Uchiyama、Leonard Kaysser、Ikuro Abe

  DOI：10.1021/jacs.1c10201

  日期：2021.11.10

  the desired stereochemistry found in the corresponding natural products. We also show that both cyclopropanases remove the 4-proS-H of 6-nitronorleucine during the cyclization, establishing the inversion and retention of the configuration at C4 during the BelL and HrmJ reactions, respectively. This study reveals the unique strategy for stereocontrolled cyclopropane synthesis in nature.

  Belactosins 和 hormaomycins 是肽天然产物，分别含有 3-(2-氨基环丙基)丙氨酸和 3-(2-硝基环丙基)丙氨酸残基，具有相反的环丙烷环立体构型。在这里，我们证明了血红素加氧酶样酶 BelK 和 HrmI 催化l-赖氨酸的 N-氧化以产生 6-硝基正亮氨酸。然后，非血红素铁酶 BelL 和 HrmJ 将硝基烷部分环化为硝基环丙烷环，并在相应的天然产物中发现所需的立体化学。我们还表明两种环丙烷酶都去除了 4 -proS环化过程中 6-硝基正亮氨酸的 -H，分别在 BelL 和 HrmJ 反应期间建立了 C4 构型的反转和保留。这项研究揭示了自然界中立体控制环丙烷合成的独特策略。
• Extension of the “ring switch” approach to glutamate antagonists to δ-lactam urethanes
  作者：Diane Coe、Martin Drysdale、Oliver Philps、Robert West、Douglas W. Young

  DOI：10.1039/b207936d

  日期：——

  The versatile “ring switching” approach to antagonists of glutamate receptors has been extended to the use of δ-lactam urethanes. Three different types of δ-lactam urethane aldehydes 17, 26 and 59 have been used successfully in this approach. Altering diastereoisomeric ratios in the synthesis by use of a hindered proton source has allowed homochiral products with two chiral centres to be obtained. Although the δ-lactam urethane system did not prove to be as versatile as the corresponding pyroglutamate or β-lactam urethanes, a variety of homologues of glutamate antagonists have been prepared.

  谷氨酸受体拮抗剂的多功能 "环状转换 "方法已扩展到δ-内酰胺氨酯的使用。三种不同类型的δ-内酰胺脲醛 17、26 和 59 已成功用于这种方法。通过使用受阻质子源来改变合成过程中的非对映异构体比例，可以获得具有两个手性中心的同手性产物。虽然事实证明δ-内酰胺氨酯体系不像相应的焦谷氨酸氨酯或δ-内酰胺氨酯那样用途广泛，但还是制备出了多种谷氨酸拮抗剂的同系物。
• 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。