dimethyl (2RS,6S)-2-hydroxy-6-[N-(benzyloxycarbonyl)-amino]heptane-1,7-dioate | 391594-67-5

• 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: dimethyl (2RS,6S)-2-hydroxy-6-[N-(benzyloxycarbonyl)-amino]heptane-1,7-dioate
• 英文别名: dimethyl (6S)-2-hydroxy-6-(phenylmethoxycarbonylamino)heptanedioate
• CAS: 391594-67-5
• 化学式: C₁₇H₂₃NO₇
• 分子量: 353.372
• InChiKey: KJAFUAMAEGKESA-LSLKUGRBSA-N

物化性质

• 沸点：
  512.0±50.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl (2RS,6S)-2-hydroxy-6-[N-(benzyloxycarbonyl)-amino]heptane-1,7-dioate 在 palladium on activated charcoal sodium hydroxide 、 四丁基氟化铵 、 氢气 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 溶剂黄146 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 23.25h， 生成 (6S,2S)-二氨基庚二酸
  参考文献：
  名称：

  Stereoselective Synthesis of meso-2,6-Diaminopimelic Acid and Its Selectively Protected Derivatives

  摘要：

  Four synthetic routes to selectively protected derivatives and isomers of meso-diaminopimelic acid (DAP) (1a), a key constituent of bacterial peptidoglycan, were investigated. N-(tert-butyloxycarbonyl)-D-allylglycine (2) and N-(benzyloxycarbonyl)-L-allylglycine (4) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7-diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N-(benzyloxycarbonyl)-L-vinylglycine moieties, such as N-(benzyloxycarbonyl)-L-glutamate or N-(benzyloxycarbonyl)-L-methionine sulfoxide, gave 12 or 15, both of which produced the alpha,beta-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl4-catalyzed ene reaction of methyl N-(benzyloxycarbonyl)-L-allylglycinate (18) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols (19 or 20). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl (6S)-2-keto-6-[N-(benzyloxycarbonyl)amino]pimelate (32) to the corresponding alcohol 33 with (S)-binaphthol-ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)-copper complex 41 as a chiral catalyst for the ene reaction of methyl (S)-4-(phenylthio)allylglycinate (39) and methyl glyoxylate to afford 42 in 94:6 isomeric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2S,6S)-6-[N(benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate (33). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N-tert-butyl [[2-(trimethylsilyl)ethyl]sulfonyl]carbamate (34) as a key step.

  DOI：

  10.1021/jo972133h
• 作为产物：
  描述：

  N-CBZ--L-烯丙基甘氨酸 在 palladium on activated charcoal 吡啶 、 氯仿 、 氢气 、 四氯化锡 作用下， 以 甲醇 为溶剂， -55.0~20.0 ℃ 、101.33 kPa 条件下， 反应 118.34h， 生成 dimethyl (2RS,6S)-2-hydroxy-6-[N-(benzyloxycarbonyl)-amino]heptane-1,7-dioate
  参考文献：
  名称：

  来自大肠杆菌的 N-琥珀酰-II-二氨基庚二酸氨基转移酶 (DAP-AT) 新型底物和抑制剂的合成与评价

  摘要：

  N-琥珀酰-LL-二氨基庚二酸氨基转移酶 (DAP-AT) (EC 2.6.1.17) 是细菌生成 L-赖氨酸途径中的关键酶，通过五个步骤从野生型大肠杆菌中纯化至接近同质（1500 倍） ATCC 9637。这种磷酸吡哆醛 (PLP) 依赖性酶的分子量为 39.9 kDa，似乎形成活性同二聚体，并使用 L-谷氨酸作为其底物 N-琥珀酰-R-氨基--酮基酮基的氨基供体酸 (1a )( K m )0.18 ( 0.04 mM, kcat ) 86 ( 5s - 1 )。在使用 L-谷氨酸脱氢酶 (EC 1.4.1.4) 的偶联酶测定中，通过分光光度法观察 NADPH 浓度在 340 nm 处的降低来监测反应进程。通过乙醛酸甲酯与 N-琥珀酰-L-烯丙基甘氨酸甲酯 (4a) 的烯反应，然后将双键氢化，醇的 Dess-Martin 氧化和小心的氢氧化锂水解，合成立体化学纯的 1a 作为其三锂盐。类似的方法允许合成一系列具有不同

  DOI：

  10.1021/ja960640v

文献信息

• The first stereospecific synthesis of l-tetrahydrodipicolinic acid†; a key intermediate of diaminopimelate metabolism
  作者：Jennifer F. Caplan、Andrew Sutherland、John C. Vederas

  DOI：10.1039/b105091p

  日期：——

  L-Tetrahydrodipicolinic acid 1, a key intermediate of diaminopimelate metabolism has been prepared in 6 steps and 23% overall yield from L-allylglycine 4. The key step during this synthesis involves a base mediated cyclisation of dimethyl (2RS,6S)-2-[N-(benzyloxycarbonyl)-N-(p-tolylsulfonyl)amino]-6-[N-(benzyloxycarbonyl)amino]heptane-1,7-dioate 8 to give (2S)-N-(benzyloxycarbonyl)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid 9. 1H NMR studies show this one pot transformation involves four steps; base elimination of toluene-p-sulfinic acid, intramolecular nucleophilic attack of the 6-benzyloxycarbonylamino group on the resulting imine, followed by hydrolysis of the esters and elimination of benzyl carbamate under acidic work-up to give the cyclic enamine 9.

  L-四氢二吡啶羧酸1是二氨基庚二酸代谢的关键中间体，已通过6步反应从L-烯丙基甘氨酸4以23%的总产率制备得到。该合成过程中的关键步骤涉及二甲基(2RS,6S)-2-[N-(苄氧羰基)-N-(对甲苯磺酰)氨基]-6-[N-(苄氧羰基)氨基]庚烷-1,7-二酸酯8的碱介导环化反应，生成(2S)-N-(苄氧羰基)-1,2,3,4-四氢吡啶-2,6-二羧酸9。1H NMR研究表明，这一步反应涉及四个步骤：对甲苯磺酸的碱消除反应、6-苄氧羰氨基团对新生成的亚胺的分子内亲核攻击、随后酯的水解以及在酸性条件下苄氧羰胺的消除，最终得到环状烯胺9。
• Synthesis and Evaluation of Novel Substrates and Inhibitors of <i>N-</i>Succinyl-<scp>ll</scp>-diaminopimelate Aminotransferase (DAP-AT) from <i>Escherichia coli</i>
  作者：Russell J. Cox、William A. Sherwin、Lister K. P. Lam、John C. Vederas

  DOI：10.1021/ja960640v

  日期：1996.1.1

  L-glutamate as the amino group donor for its substrate, N-succinyl-R-amino- -ketopimelic acid (1a )( K m )0.18 ( 0.04 mM, kcat ) 86 ( 5s - 1 ). Progress of the reaction is monitored by spectrophotometric observation of decrease in NADPH concentration at 340 nm in a coupled enzyme assay with L-glutamate dehydrogenase (EC 1.4.1.4). Stereochemically pure 1a was synthesized as its trilithium salt by ene reaction

  N-琥珀酰-LL-二氨基庚二酸氨基转移酶 (DAP-AT) (EC 2.6.1.17) 是细菌生成 L-赖氨酸途径中的关键酶，通过五个步骤从野生型大肠杆菌中纯化至接近同质（1500 倍） ATCC 9637。这种磷酸吡哆醛 (PLP) 依赖性酶的分子量为 39.9 kDa，似乎形成活性同二聚体，并使用 L-谷氨酸作为其底物 N-琥珀酰-R-氨基--酮基酮基的氨基供体酸 (1a )( K m )0.18 ( 0.04 mM, kcat ) 86 ( 5s - 1 )。在使用 L-谷氨酸脱氢酶 (EC 1.4.1.4) 的偶联酶测定中，通过分光光度法观察 NADPH 浓度在 340 nm 处的降低来监测反应进程。通过乙醛酸甲酯与 N-琥珀酰-L-烯丙基甘氨酸甲酯 (4a) 的烯反应，然后将双键氢化，醇的 Dess-Martin 氧化和小心的氢氧化锂水解，合成立体化学纯的 1a 作为其三锂盐。类似的方法允许合成一系列具有不同
• Stereoselective Synthesis of <i>meso</i>-2,6-Diaminopimelic Acid and Its Selectively Protected Derivatives
  作者：Yong Gao、Patricia Lane-Bell、John C. Vederas

  DOI：10.1021/jo972133h

  日期：1998.4.1

  Four synthetic routes to selectively protected derivatives and isomers of meso-diaminopimelic acid (DAP) (1a), a key constituent of bacterial peptidoglycan, were investigated. N-(tert-butyloxycarbonyl)-D-allylglycine (2) and N-(benzyloxycarbonyl)-L-allylglycine (4) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7-diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N-(benzyloxycarbonyl)-L-vinylglycine moieties, such as N-(benzyloxycarbonyl)-L-glutamate or N-(benzyloxycarbonyl)-L-methionine sulfoxide, gave 12 or 15, both of which produced the alpha,beta-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl4-catalyzed ene reaction of methyl N-(benzyloxycarbonyl)-L-allylglycinate (18) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols (19 or 20). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl (6S)-2-keto-6-[N-(benzyloxycarbonyl)amino]pimelate (32) to the corresponding alcohol 33 with (S)-binaphthol-ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)-copper complex 41 as a chiral catalyst for the ene reaction of methyl (S)-4-(phenylthio)allylglycinate (39) and methyl glyoxylate to afford 42 in 94:6 isomeric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2S,6S)-6-[N(benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate (33). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N-tert-butyl [[2-(trimethylsilyl)ethyl]sulfonyl]carbamate (34) as a key step.