dimethyl (2S,5E)-N,N-di-tert-butoxycarbonyl-2-aminohept-5-ene-dioate | 219617-06-8

• 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: dimethyl (2S,5E)-N,N-di-tert-butoxycarbonyl-2-aminohept-5-ene-dioate
• 英文别名: dimethyl (E,6S)-6-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]hept-2-enedioate
• CAS: 219617-06-8
• 化学式: C₁₉H₃₁NO₈
• 分子量: 401.457
• InChiKey: WLQQNJHYBKNEFM-XSNHNAGMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dimethyl (2S,5E)-N,N-di-tert-butoxycarbonyl-2-aminohept-5-ene-dioate 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以93%的产率得到dimethyl (2S)-2-{(tert-butoxy)-N-[(tert-butyl)oxycarbonyl]carbonylamino}heptanedioate
  参考文献：
  名称：

  Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

  摘要：

  The enantiospecific synthesis of unnatural unsaturated and saturated alpha-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, L-glutamic and L-aspartic acid semialdehydes, are obtained from the corresponding N,N-di-Boc-diesters, by the selective reduction of the omega'-ester with DIBAL(R) under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated alpha-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(98)00354-1
• 作为产物：
  描述：

  谷氨酸二甲酯 在 4-二甲氨基吡啶 、 二异丁基氢化铝 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 正己烷 、 乙腈 、 苯 为溶剂， 反应 0.08h， 生成 dimethyl (2S,5E)-N,N-di-tert-butoxycarbonyl-2-aminohept-5-ene-dioate
  参考文献：
  名称：

  Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

  摘要：

  The enantiospecific synthesis of unnatural unsaturated and saturated alpha-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, L-glutamic and L-aspartic acid semialdehydes, are obtained from the corresponding N,N-di-Boc-diesters, by the selective reduction of the omega'-ester with DIBAL(R) under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated alpha-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(98)00354-1

文献信息

• The stereoselective synthesis of aziridine analogues of diaminopimelic acid (DAP) and their interaction with dap epimerase
  作者：Christopher M. Diaper、Andrew Sutherland、Bindu Pillai、Michael N. G. James、Paul Semchuk、John S. Blanchard、John C. Vederas

  DOI：10.1039/b513409a

  日期：——

  Aziridine analogues of diaminopimelic acid (DAP) have been prepared stereoselectively for the first time and evaluated as inhibitors of DAP epimerase. (2R,3S,3′S)-3-(3′-Aminopropane)aziridine-2,3′-dicarboxylate 4 was synthesised and shown to be a reversible inhibitor of DAP epimerase with an IC50 value of 2.88 mM. (2S,4S)- and (2S,4R)-2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid (LL-azi-DAP 14 and DL-azi-DAP 29) were made as pure diastereomers, and both were shown to be irreversible inhibitors of DAP epimerase. LL-Azi-DAP 14 selectively binds to Cys-73 of the enzyme active site whereas DL-azi-DAP 29 binds to Cys-217 via attack of sulfhydryl on the methylene of the inhibitor aziridine ring. These observations are consistent with the two base mechanism proposed for the epimerisation of LL-DAP 1 and meso-DAP 2 by DAP epimerase.

  我们首次立体选择性地制备了二氨基亚庚酸（DAP）的氮丙啶类似物，并将其评估为 DAP 外切酶的抑制剂。合成了(2R,3S,3′S)-3-(3′-氨基丙烷)氮丙啶-2,3′-二甲酸酯 4，结果表明它是 DAP 表聚酶的可逆抑制剂，IC50 值为 2.88 mM。(2S,4S)-和(2S,4R)-2-(4-氨基-4-羧基丁基)氮丙啶-2-羧酸（LL-Azi-DAP 14 和 DL-azi-DAP 29）被制成纯非对映异构体，并被证明都是 DAP 表聚酶的不可逆抑制剂。LL-azi-DAP 14 可选择性地与酶活性位点的 Cys-73 结合，而 DL-azi-DAP 29 则通过巯基对抑制剂氮丙啶环亚甲基的攻击与 Cys-217 结合。这些观察结果与 DAP 表聚酶对 LL-DAP 1 和 meso-DAP 2 的表聚作用提出的双基机制是一致的。
• Unsaturated α-aminopimelic acids as potent inhibitors of meso-diaminopimelic acid (DAP) D-dehydrogenase
  作者：Andrew Sutherland、Jennifer F. Caplan、John C. Vederas

  DOI：10.1039/a900297i

  日期：——

  Two nonproteinogenic amino acids 5 and 6 have been efficiently prepared using an SH2′ allylstannane coupling reaction and a Wittig reaction, respectively, to effect the key steps; kinetic studies show these compounds to be reversible inhibitors of DAP dehydrogenase with Ki values of 5.3 (competitive) and 44 µM (noncompetitive), respectively.

  利用 SH2â² 烯丙基锡烷偶联反应和 Wittig 反应分别高效制备了两种非蛋白源氨基酸 5 和 6，以实现关键步骤；动力学研究表明，这些化合物是 DAP 脱氢酶的可逆抑制剂，其 Ki 值分别为 5.3（竞争性）和 44 μM（非竞争性）。
• Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids
  作者：José M Padrón、George Kokotos、Tomás Martı́n、Theodoros Markidis、William A Gibbons、Vı́ctor S Martı́n

  DOI：10.1016/s0957-4166(98)00354-1

  日期：1998.10

  The enantiospecific synthesis of unnatural unsaturated and saturated alpha-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, L-glutamic and L-aspartic acid semialdehydes, are obtained from the corresponding N,N-di-Boc-diesters, by the selective reduction of the omega'-ester with DIBAL(R) under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated alpha-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation. (C) 1998 Elsevier Science Ltd. All rights reserved.