di(tert-butyl) (2S,4S)-4-hydroxy-6-oxo-1,2-piperidinedicarboxylate | 653589-16-3

• 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,4S)-4-hydroxy-6-oxo-1,2-piperidinedicarboxylate
• 英文别名: Di-tert-butyl (2S,4S)-4-hydroxy-6-oxopiperidine-1,2-dicarboxylate；ditert-butyl (2S,4S)-4-hydroxy-6-oxopiperidine-1,2-dicarboxylate
• CAS: 653589-16-3
• 化学式: C₁₅H₂₅NO₆
• 分子量: 315.367
• InChiKey: PKKJGCFMTULNMV-UWVGGRQHSA-N

物化性质

• 熔点：
  128-129 °C
• 沸点：
  448.1±45.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di(tert-butyl) (2S,4S)-4-hydroxy-6-oxo-1,2-piperidinedicarboxylate 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 以100%的产率得到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：

  N-叔丁氧羰基-L-天冬氨酸 1-叔丁酯 在 4-二甲氨基吡啶 、 sodium cyanoborohydride 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 80.0h， 生成 di(tert-butyl) (2S,4S)-4-hydroxy-6-oxo-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

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。
• 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 a Galactosylated 4-Hydroxylysine Building Block and Its Incorporation into a Collagen Immunodominant Glycopeptide
  作者：Julien Marin、Jean-Paul Briand、Gilles Guichard

  DOI：10.1002/ejoc.200700806

  日期：2008.2

  An analogue of the immunodominant glycopeptide from type II collagen encompassing residues 256–270 has been prepared by substituting β-D-galactopyranosyl-(2S,4R)-4-hydroxy-L-lysyl (Gal-4-Hyl) for β-D-galactopyranosyl-(2S,5R)-5-hydroxy-L-lysyl (Gal-5-Hyl) at position 264. The synthesis of the 4-hydroxylysine aglycon started from the known (2S,4S)-4-hydroxy-6-oxo-1,2-piperidinedicarboxylate (3) and involved

  通过用 β-D-吡喃半乳糖基-(2S,4R)-4-羟基-L-赖氨酰 (Gal-4-Hyl) 代替 β-D 制备了来自 II 型胶原蛋白的免疫显性糖肽类似物，包含残基 256-270 -吡喃半乳糖基-(2S,5R)-5-羟基-L-赖氨酰 (Gal-5-Hyl) 在 264 位。 4-羟基赖氨酸苷元的合成从已知的 (2S,4S)-4-羟基-6 开始-oxo-1,2-piperidinedicarboxylate (3) 并涉及 3 的选择性开环、内酯形成和内酯与甘氨酯的 N-酰化。得到的 N-Fmoc 保护的 4-羟基赖氨酰-甘氨酸二肽衍生物以高产率进行半乳糖基化，得到适合固相肽合成的结构单元。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
• 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
  作者：Chaloin, Olivier、Cabart, Frédéric、Marin, Julien、Zhang, Haixiang、Guichard, Gilles、Shibasaki, Masakatsu、Mihara, Hisashi

  DOI：10.15227/orgsyn.085.0147

  日期：——
• 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).