N-<(S)-4-(p-methoxybenzyloxycarbonylamino)-2-hydroxybutanoyloxy>succinimide | 81144-42-5

• 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: N-<(S)-4-(p-methoxybenzyloxycarbonylamino)-2-hydroxybutanoyloxy>succinimide
• 英文别名: (S)-4-p-methoxybenzyloxycarbonylamino-2-hydroxybutanoic acid N-hydroxysuccinimide ester；(2,5-dioxopyrrolidin-1-yl) (2S)-2-hydroxy-4-[(4-methoxyphenyl)methoxycarbonylamino]butanoate
• CAS: 81144-42-5
• 化学式: C₁₇H₂₀N₂O₈
• 分子量: 380.354
• InChiKey: BYXXSAGYMVGXTO-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.28
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  131.47
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-<(S)-4-(p-methoxybenzyloxycarbonylamino)-2-hydroxybutanoyloxy>succinimide 在 吡啶 、 ammonium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Synthesis of 5-deoxy-5-epifluoro derivatives of arbekacin, amikacin, and 1-N-[(S)-4-amino-2-hydroxybutanoyl]tobramycin (study on structure — toxicity relationships)

  摘要：

  As part of a study on fluorination-toxicity relationships for aminoglycoside antibiotics, 5,3'-dideoxy-5-epifluorokanamycin B (10), 5,3',4'-trideoxy-5-epifluorokanamycin B (11), 1-N-[(S)-4-amino-2-hydroxybutanoyl]-5-deoxy-5-epifluorotobramycin (19), 5-deoxy-5-epifluoroarbekacin (20), and 5-deoxy-5-epifluoroamikacin (21) have been prepared. The acute toxicities of these three 5-deoxy-5-epifluoro compounds showed values almost identical or similar to those for arbekacin (ABK) and amikacin (15), making a sharp contrast with the toxicities of the corresponding 5-deoxy-5-fluoro derivatives. This fact is explained on the basis of basicity changes (retention for the 5-epifluoro derivatives and reduction for the 5-fluoro derivatives) at the H2N-3 groups of the fluorinated compounds compared to the parent compounds; this hypothesis was substantiated by the pKa values at the H3N+-1, 3 groups (determined by the shift changes depending on pD values at C-2 and C-4, 6 in their C-13 NMR spectral of 2,5-dideoxy-5-epifluorostreptamine (23) and 2,5-dideoxy-5-fluorostreptamine (24), chosen as model compounds, and 2-deoxystreptamine (DST).

  DOI：

  10.1016/0008-6215(95)00123-b
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 (S)-4-[(p-methoxybenzyloxycarbonyl)amino]-2-hydroxybutyric acid 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 N-<(S)-4-(p-methoxybenzyloxycarbonylamino)-2-hydroxybutanoyloxy>succinimide
  参考文献：
  名称：

  Synthesis of 2"-amino-2"-deoxyarbekacin and its analogs having potent activity against methicillin-resistant Staphylococcus aureus.

  摘要：

  根据我们对耐甲氧西林金黄色葡萄球菌（MRSA）对阿贝卡信酶修饰的研究，设计了将阿贝卡信的2"-羟基替换为氨基，以合成对MRSA具有活性的衍生物。从二贝卡信出发合成了2"-氨基-2"-脱氧阿贝卡信及五个类似物。其中，2"-氨基-2"-脱氧阿贝卡信和5-表氨基类似物对MRSA及包括铜绿假单胞菌在内的革兰氏阴性细菌表现出优异的抗菌活性，并且其毒性低于阿贝卡信。

  DOI：

  10.7164/antibiotics.47.821

文献信息

• Synthesis of 2"-amino-2"-deoxyarbekacin and its analogs having potent activity against methicillin-resistant Staphylococcus aureus.
  作者：SHINICHI KONDO、YOKO IKEDA、DAISHIRO IKEDA、TOMIO TAKEUCHI、TAKAYUKI USUI、MIYUKI ISHII、TOSHIAKI KUDO、SHUICHI GOMI、SEUI SHIBAHARA

  DOI：10.7164/antibiotics.47.821

  日期：——

  Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2"-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2"-Amino-2"-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2"-amino-2"-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.

  根据我们对耐甲氧西林金黄色葡萄球菌（MRSA）对阿贝卡信酶修饰的研究，设计了将阿贝卡信的2"-羟基替换为氨基，以合成对MRSA具有活性的衍生物。从二贝卡信出发合成了2"-氨基-2"-脱氧阿贝卡信及五个类似物。其中，2"-氨基-2"-脱氧阿贝卡信和5-表氨基类似物对MRSA及包括铜绿假单胞菌在内的革兰氏阴性细菌表现出优异的抗菌活性，并且其毒性低于阿贝卡信。
• Synthesis and antibacterial activity of novel neamine derivatives
  作者：Nobuto Minowa、Yoshihisa Akiyama、Yukiko Hiraiwa、Kazunori Maebashi、Takayuki Usui、Daishiro Ikeda

  DOI：10.1016/j.bmcl.2006.09.007

  日期：2006.12

  Synthesis and activity of derivatives at the O5 or O6 positions of 1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxyneamine, which is the neamine moiety of arbekacin, were reported. Among these results, the 5-O-aminoethylaminocarbonyl derivative showed effective activity against Staphylococcus aureus expressing a bifunctional aminoglycoside-modifying enzyme AAC(6')APH(2"). (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis of 5-deoxy-5-epifluoro derivatives of arbekacin, amikacin, and 1-N-[(S)-4-amino-2-hydroxybutanoyl]tobramycin (study on structure — toxicity relationships)
  作者：Tetsuo Shitara、Eijiro Umemura、Tsutomu Tsuchiya、Tomio Matsuno

  DOI：10.1016/0008-6215(95)00123-b

  日期：1995.10

  As part of a study on fluorination-toxicity relationships for aminoglycoside antibiotics, 5,3'-dideoxy-5-epifluorokanamycin B (10), 5,3',4'-trideoxy-5-epifluorokanamycin B (11), 1-N-[(S)-4-amino-2-hydroxybutanoyl]-5-deoxy-5-epifluorotobramycin (19), 5-deoxy-5-epifluoroarbekacin (20), and 5-deoxy-5-epifluoroamikacin (21) have been prepared. The acute toxicities of these three 5-deoxy-5-epifluoro compounds showed values almost identical or similar to those for arbekacin (ABK) and amikacin (15), making a sharp contrast with the toxicities of the corresponding 5-deoxy-5-fluoro derivatives. This fact is explained on the basis of basicity changes (retention for the 5-epifluoro derivatives and reduction for the 5-fluoro derivatives) at the H2N-3 groups of the fluorinated compounds compared to the parent compounds; this hypothesis was substantiated by the pKa values at the H3N+-1, 3 groups (determined by the shift changes depending on pD values at C-2 and C-4, 6 in their C-13 NMR spectral of 2,5-dideoxy-5-epifluorostreptamine (23) and 2,5-dideoxy-5-fluorostreptamine (24), chosen as model compounds, and 2-deoxystreptamine (DST).