2,5-anhydro-N-benzyloxycarbonyl-2,5-imino-D-glucitol | 191851-89-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,5-anhydro-N-benzyloxycarbonyl-2,5-imino-D-glucitol
• 英文别名: 2(R),5(R)-bis(hydroxymethyl)-3(R),4(S)-dihydroxy-N-(benzyloxycarbonyl)-pyrrolidine；benzyl (2R,3R,4R,5S)-3,4-dihydroxy-2,5-bis(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 191851-89-5
• 化学式: C₁₄H₁₉NO₆
• 分子量: 297.308
• InChiKey: KYZBLULKAPLALD-YVECIDJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,5-anhydro-N-benzyloxycarbonyl-2,5-imino-D-glucitol 在 咪唑 、 高氯酸 、 碘 、 溶剂黄146 、 三苯基膦 、 丙酮 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2,5-anhydro-1-deoxy-N-benzyloxycarbonyl-4,6-di-O-tert-butyldiphenylsilyl-1-iodo-2,5-imino-D-glucitol
  参考文献：
  名称：

  阿拉伯糖的同源氮杂类似物作为抗分枝杆菌剂。

  摘要：

  制备了一系列阿拉伯呋喃糖水解稳定的氮杂类似物，并针对结核分枝杆菌和鸟分枝杆菌进行了评估。设计这些化合物以模拟参与必需细胞壁多糖阿拉伯半乳聚糖的生物发生的推定的阿拉伯糖供体。尽管大多数化合物在细胞培养中显示很少的活性，但一种化合物在感染的巨噬细胞模型中显示了显着的活性。

  DOI：

  10.1016/s0960-894x(98)00017-1
• 作为产物：
  描述：

  2,5-二(羟基甲基)-3,4-吡咯烷二醇 、 氯甲酸苄酯 在 碳酸氢钠 作用下， 以 1,4-二氧六环 为溶剂， 生成 2,5-anhydro-N-benzyloxycarbonyl-2,5-imino-D-glucitol
  参考文献：
  名称：

  阿拉伯糖的同源氮杂类似物作为抗分枝杆菌剂。

  摘要：

  制备了一系列阿拉伯呋喃糖水解稳定的氮杂类似物，并针对结核分枝杆菌和鸟分枝杆菌进行了评估。设计这些化合物以模拟参与必需细胞壁多糖阿拉伯半乳聚糖的生物发生的推定的阿拉伯糖供体。尽管大多数化合物在细胞培养中显示很少的活性，但一种化合物在感染的巨噬细胞模型中显示了显着的活性。

  DOI：

  10.1016/s0960-894x(98)00017-1

文献信息

• HIV protease inhibitors
  申请人：Wong Chi-Huey

  公开号：US06900238B1

  公开（公告）日：2005-05-31

  Combinatorial libraries of HIV and FIV protease inhibitors are characterized by α-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.

  HIV和FIV蛋白酶抑制剂的组合库以α-酮酰胺或羟乙基胺核心结构为特征，一侧为取代吡咯烷、哌啶或氮代糖，另一侧为苯丙氨酸、酪氨酸或取代酪氨酸。这些库是通过一步偶联反应合成的。通过筛选这些库，识别出对HIV和FIV蛋白酶的结合和抑制活性高效的药物候选化合物。对HIV和FIV蛋白酶都显示出临床有用活性的药物候选化合物被确定为潜在对抗由于HIV耐药株的发展而导致的抑制活性丧失。
• Homologated aza analogs of arabinose as antimycobacterial agents
  作者：Joseph A. Maddry、Namita Bansal、Luiz E. Bermudez、Robert N. Comber、Ian M. Orme、William J. Suling、Larry N. Wilson、Robert C. Reynolds

  DOI：10.1016/s0960-894x(98)00017-1

  日期：1998.2

  A series of hydrolytically-stable aza analogs of arabinofuranose was prepared and evaluated against Mycobacterium tuberculosis and M. avium. The compounds were designed to mimic the putative arabinose donor involved in biogenesis of the essential cell wall polysaccharide, arabinogalactan. Though most compounds displayed little activity in cell culture, one compound showed significant activity in infected

  制备了一系列阿拉伯呋喃糖水解稳定的氮杂类似物，并针对结核分枝杆菌和鸟分枝杆菌进行了评估。设计这些化合物以模拟参与必需细胞壁多糖阿拉伯半乳聚糖的生物发生的推定的阿拉伯糖供体。尽管大多数化合物在细胞培养中显示很少的活性，但一种化合物在感染的巨噬细胞模型中显示了显着的活性。
• Aglycon mimicking: Glycoside bond cleavage transition state mimics based on hydroxypyrrolidine inhibitors
  作者：Gitte Mikkelsen、Troels V. Christensen、Mikael Bols、Inge Lundt、Michael R. Sierks

  DOI：10.1016/0040-4039(95)01281-l

  日期：1995.9

  beta-L-xylopyranosides of a number of both known and new hydroxypyrrolidines were prepared.
• Selectivity in the Inhibition of HIV and FIV Protease: Inhibitory and Mechanistic Studies of Pyrrolidine-Containing .alpha.-Keto Amide and Hydroxyethylamine Core Structures
  作者：Deborah H. Slee、Karen L. Laslo、John H. Elder、Ian R. Ollmann、Alla Gustchina、Jukka Kervinen、Alexander Zdanov、Alexander Wlodawer、Chi-Huey Wong

  DOI：10.1021/ja00153a008

  日期：1995.12

  This paper describes the development of new pyrrolidine-containing alpha-keto amide and hydroxyethylamine core structures as mechanism based inhibitors of the HIV and FIV proteases. It was found that the alpha-keto amide core structure 2 is approximately 300-fold better than the corresponding hydroxyethylamine isosteric structure and 1300-fold better than the corresponding phosphinic acid derivative as an inhibitor of the HIV protease. The alpha-keto amide is however not hydrated until it is bound to the HIV protease as indicated by the NMR study and the X-ray structural analysis. Further analysis of the inhibition activities of hydroxyethylamine isosteres containing modified pyrrolidine derivatives revealed that a cis-methoxy group at C-4 of the pyrrolidine would improve the binding 5-and 25-fold for the trans-isomer. When this strategy was applied to the alpha-keto amide isostere, a cis-benzyl ether at C-4 was found to enhance binding 3-fold. Of the core structures prepared as inhibitors of the HIV protease, none show significant inhibitory activity against the mechanistically identical FIV protease, and additional complementary groups are needed to improve inhibition.
• Ethambutol–sugar hybrids as potential inhibitors of mycobacterial cell-wall biosynthesis
  作者：Robert C Reynolds、Namita Bansal、Jerry Rose、Joyce Friedrich、William J Suling、Joseph A Maddry

  DOI：10.1016/s0008-6215(99)00069-5

  日期：1999.4

  Ethambutol is an established front-line agent for the treatment of tuberculosis, and is also active against Mycobacterium avium infection. However, this agent exhibits toxicity, and is considered to have low potency. The action of ethambutol on the mycobacterial cell wall, particularly the arabinan, and comparison of the structure of ethambutol with several of the cell-wall saccharides, suggested that ethambutol-saccharide hybrids might lead to agents with a more selective mechanism of action. To this end, eight ethambutol-saccharide hybrids were synthesized and screened against M. tuberculosis and several clinical isolates of M. avium. (C) 1999 Elsevier Science Ltd. All rights reserved.