dibenzyl-2,4-dihydroxyphenylacetic acid N-hydroxysuccinimide ester | 113978-98-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: dibenzyl-2,4-dihydroxyphenylacetic acid N-hydroxysuccinimide ester
• 英文别名: 2,4-dibenzyloxyphenylacetic acid N-hydroxysuccinimidyl ester；2,4-dibenzyloxyphenylacetic acid N-hydroxysuccinimide ester；2,4-bis(benzyloxy)phenylacetic acid succinimidyl ester；(2,4-dibenzyloxyphenyl)acetic acid succinimidyl ester；2,4-dibenzyloxyphenylacetic acid succinimide ester；hydroxysuccinimide-2,4-dibenzyloxyphenylacetate；(2,5-Dioxopyrrolidin-1-yl) 2-[2,4-bis(phenylmethoxy)phenyl]acetate
• CAS: 113978-98-6
• 化学式: C₂₆H₂₃NO₆
• 分子量: 445.472
• InChiKey: IFFXHBDFLGFIRU-UHFFFAOYSA-N

物化性质

• 沸点：
  613.4±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dibenzyl-2,4-dihydroxyphenylacetic acid N-hydroxysuccinimide ester 在 palladium dihydroxide 草酰氯 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 22.0h， 生成 Argiotoxin 636
  参考文献：
  名称：

  通过实用的还原烷基化策略全合成多胺酰胺蜘蛛毒素argiotoxin-636

  摘要：

  还原性烷基化是蜘蛛毒素argiotoxin 636（一种多胺酰胺，它是一种选择性的谷氨酸受体拮抗剂）的全合成的实用策略，可能具有神经保护剂的潜力。该合成的关键是Swern氧化和还原性烷基化。

  DOI：

  10.1016/0040-4039(95)01994-s
• 作为产物：
  描述：

  2,4-二羟基苯甲酸 在 sodium hydroxide 、 sodium hydride 作用下， 生成 dibenzyl-2,4-dihydroxyphenylacetic acid N-hydroxysuccinimide ester
  参考文献：
  名称：

  Synthesis of a new neurotoxin NSTX-3 of Papua New Guinean spider

  摘要：

  DOI：

  10.1016/s0040-4039(00)96339-1

文献信息

• Study on the Structure Activity Relationships of NPTX-594, a Spider Toxin Belonging to the Type-B Acylpolyamine Structure
  作者：Tateaki Wakamiya、Tomohiko Kinoshita、Yoshihide Hattori、Yoshihiro Yamaguchi、Hideo Naoki、Gerardo Corzo、Terumi Nakajima

  DOI：10.1246/bcsj.77.331

  日期：2004.2

  In order to elucidate the structure activity relationships of the spider toxin termed NPTX-594, eleven toxin analogs were designed and synthesized, and their paralytic activities against cricket we...

  为了阐明被称为 NPTX-594 的蜘蛛毒素的构效关系，设计并合成了 11 种毒素类似物，以及它们对蟋蟀的麻痹活性...
• Total Syntheses of Spidamine and Joramine, Polyamine Toxins from the Joro Spider, Nephila clavata.
  作者：Tadashige CHIBA、Toshifumi AKIZAWA、Motomi MATSUKAWA、Masatoshi NISHI、Nobufumi KAWAI、Masanori YOSHIOKA

  DOI：10.1248/cpb.44.972

  日期：——

  In order to confirm the structures of spidamine and joramine, identified from the venom of a spider (Nephila clavata), we convergently synthesized both compounds, which have a common side chain of N-(L-asparaginyl)-N'-(3-aminopropyl-β-alanyl)-1, 5-pentanediamine. A synthon of the common side chain was synthesized by starting with n-propanolamine which was converted to 7-azido-N-benzyloxycarbonyl-4-azaheptanoic acid N-hydroxysuccinimidyl ester. The ester was coupled with tert-butyloxycarbonyl-L-asparaginyl-1, 5-pentanediamine to give the synthon of the common side chain. In the final synthesis of spidamine, the synthon of the common side chain was reacted with 2, 4-dibenzyloxyphenylacetic acid N-hydroxysuccinimidyl ester, obtained by Willgerodt-Kindler reaction of 2, 4-dihydroxyacetophenone. The protected spidamine was catalytically hydrogenated to remove protective groups, affording spidamine itself in 13% yield from n-propanolamine. In the final synthesis of joramine, the synthon of the common side chain was reacted with 4-benzyloxyphenyl acetic acid N-hydroxysuccinimidyl ester. The protected joramine was also catalytically hydrogenated to produce joramine itself in 11% yield.The conformations of both synthesized compounds were analyzed by 1H-NMR and 13C-NMR. Their blocking activities on glutamate receptors were examined using labster neuromuscular synapses.

  为了确认从蜘蛛（Nephila clavata）毒液中鉴定出的spidamine和joramine的结构，我们收敛性地合成了这两种化合物，它们具有共同的侧链N-(L-天冬酰胺基)-N'-(3-氨基丙基-β-丙氨酸)-1, 5-戊二胺。通过以n-丙醇胺为起始材料合成了共同侧链的合成单元，该物质被转化为7-叠氮-N-苄氧羧酸-4-氮杂庚酸N-羟基琥珀酰亚胺酯。这个酯与tert-丁氧羧基-L-天冬酰胺-1, 5-戊二胺偶联，得到共同侧链的合成单元。在spidamine的最终合成中，共同侧链的合成单元与由Willgerodt-Kindler反应2, 4-二羟基乙酰苯酮得到的2, 4-二苄氧基苯乙酸N-羟基琥珀酰亚胺酯反应。保护型的spidamine经过催化氢化以去除保护基团，最终得到了spidamine，其产率为从n-丙醇胺起始物的13%。在joramine的最终合成中，共同侧链的合成单元与4-苄氧基苯乙酸N-羟基琥珀酰亚胺酯反应。保护型的joramine同样经过催化氢化以生成joramine，本体的产率为11%。通过1H-NMR和13C-NMR分析了这两种合成化合物的构象。利用实验室神经肌肉突触考察了它们对谷氨酸受体的阻断活性。
• Syntheses and Biological Activities of Joro Spider Toxin Analogs to Spidamine and Joramine.
  作者：Tadashige CHIBA、Toshifumi AKIZAWA、Motomi MATSUKAWA、Nobufumi KAWAI、Yoshiaki KONO、Masanori YOSHIOKA

  DOI：10.1248/cpb.45.93

  日期：——

  In order to study the structure-activity relationships of spidamine and joramine found in the venom of Joro spider, Nephila clavata, we attempted to synthesize various analogs. Six analogs were convergently synthesized according to our previous method for the synthesis of spidamine, N-(3-aminopropyl-β-alanyl)-N'-(2, 4-dihydroxy-phenylacetyl-L-asparaginyl)-1, 5-pentanediamine and joramine, N-(3-aminopropyl-β-alanyl)-N'-(4-hydroxyphenyl-acetyl-L-asparaginyl)-1, 5-pentanediamine. The biological activities of the analogs and four intermediates were compared with those of synthetic spidamine and joramine in three bioassay systems, lobster neuromuscular synapse, cockroaches and mosquito larvae. The glutamate receptors in these systems were inhibited by some analogs, and the D-asparagine- or indoleacetyl-containing analogs were found to be strong inhibitors. These compounds have potential application as insecticides.

  为了研究在Joro蜘蛛（Nephila clavata）毒液中发现的spidamine和joramine的结构-活性关系，我们尝试合成各种类似物。根据我们之前合成spidamine的的方法，我们共合成了六种类似物，分别是N-(3-氨基丙基-β-丙氨酸)-N'-(2, 4-二羟基苯乙酰-L-天冬氨酰)-1, 5-戊二胺和joramine，N-(3-氨基丙基-β-丙氨酸)-N'-(4-羟基苯乙酰-L-天冬氨酰)-1, 5-戊二胺。这些类似物及四种中间体的生物活性与合成的spidamine和joramine在三种生物测定系统中进行了比较，包括龙虾神经肌肉突触、蟑螂和蚊子幼虫。在这些系统中，某些类似物抑制了谷氨酸受体，而含有D-天冬氨酸或吲哚乙酰的类似物被发现是强抑制剂。这些化合物在农药方面具有潜在应用前景。
• Practical, convergent total synthesis of polyamine amide spider toxin NSTX-3
  作者：Ian S Blagbrough、Eduardo Moya、Steven P Walford

  DOI：10.1016/0040-4039(95)02238-4

  日期：1996.1

  A practical, total synthesis of polyamine amide spider toxin NSTX-3, a potent glutamate receptor antagonist with potential as a neuroprotective agent, is reported. The unsymmetrical polyamine motiety was built by a conjugate addition to afford putreamine and regioselective acylation of L-asparaginyl-cadaverine.

  报道了一种实用的，全合成的多胺酰胺蜘蛛毒素NSTX-3，一种有效的谷氨酸受体拮抗剂，具有潜在的神经保护作用。通过共轭加成来建立不对称的多胺部分，以提供L-天冬酰胺基-尸胺的腐胺和区域选择性酰化。
• Total Synthesis of the Novel Spider Toxin NPTX-594 from<i>Nephila madagascariencis</i>
  作者：Tateaki Wakamiya、Akinori Yamamoto、Keita Kawaguchi、Tomohiko Kinoshita、Yoshihiro Yamaguchi、Yasuhiro Itagaki、Hideo Naoki、Terumi Nakajima

  DOI：10.1246/bcsj.74.1743

  日期：2001.9

  A novel spider toxin, NPTX-594, comprised of four constituents: i.e., 2,4-dihydroxyphenylacetic acid (Dhpa), asparagine, 4,8-diaza-1,12-dodecanediamine (Dada), and lysine, was chemically synthesized. The synthetic compound was completely identical with the natural product as regards 1H NMR and mass spectra. The structure of NPTX-594 was thus determined synthetically to be N12-(Dhpa-Asn)-N1-Lys-Dada

  化学合成了一种新型蜘蛛毒素 NPTX-594，它由四种成分组成：即 2,4-二羟基苯乙酸 (Dhpa)、天冬酰胺、4,8-二氮杂-1,12-十二烷二胺 (Dada) 和赖氨酸。合成化合物的 1H NMR 和质谱与天然产物完全相同。NPTX-594 的结构因此综合确定为 N12-(Dhpa-Asn)-N1-Lys-Dada，如光谱分析所建议的。