N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-α-D-fucoside | 1256382-18-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-α-D-fucoside
• 英文别名: N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-D-fucoside；(2S,3R,4S,5R,6R)-2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butyl-hydroxyamino]-6-methyloxane-3,4,5-triol
• CAS: 1256382-18-9
• 化学式: C₂₀H₃₂Cl₂N₂O₅
• 分子量: 451.39
• InChiKey: NBLNTURSWQHMRB-OITRIXBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  96.6
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  D-Fucose 、 N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamine 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 (2S,3R,4S,5R,Z)-N-(4-(4-(bis(2-chloroethyl)amino)phenyl)butyl)-2,3,4,5-tetrahydroxyhexan-1-imine oxide 、 N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-β-D-fucoside 、 N-hydroxy-4-(4-N',N'-bis(2-chloroethyl)amino)phenylbutylamino-α-D-fucoside
  参考文献：
  名称：

  Assessment of Chemoselective Neoglycosylation Methods Using Chlorambucil as a Model

  摘要：

  To systematically assess the impact of glycosylation and the corresponding chemoselective linker upon the anticancer activity/selectivity of the drug chlorambucil, herein we report the synthesis and anticancer activities of a 63-member library of chlorambucil-based neoglycosides. A comparison of N-alkoxyamine-. N-acylhydrazine-, and N-hydroxyamine-based chemoselective glycosylation of chlorambucil revealed sugar- and linker-dependent partitioning among open- and closed-ring neoglycosides and corresponding sugar-dependent variant biological activity. Cumulatively, this study represents the First neoglycorandomization of a synthetic drug and expands our understanding of the impact of sugar structure upon product distribution/equilibria in the context of N-alkoxyamino-, N-hydroxyamino-, and N-acylhydrazine-based chemoselective glycosylation. This study also revealed several analogues with increased in vitro anticancer activity, most notably D-threoside 60 (NSC 748747), which displayed much broader tumor specificity and notably increased potency over the parent drug.

  DOI：

  10.1021/jm101024j

文献信息

• Assessment of Chemoselective Neoglycosylation Methods Using Chlorambucil as a Model
  作者：Randal D. Goff、Jon S. Thorson

  DOI：10.1021/jm101024j

  日期：2010.11.25

  To systematically assess the impact of glycosylation and the corresponding chemoselective linker upon the anticancer activity/selectivity of the drug chlorambucil, herein we report the synthesis and anticancer activities of a 63-member library of chlorambucil-based neoglycosides. A comparison of N-alkoxyamine-. N-acylhydrazine-, and N-hydroxyamine-based chemoselective glycosylation of chlorambucil revealed sugar- and linker-dependent partitioning among open- and closed-ring neoglycosides and corresponding sugar-dependent variant biological activity. Cumulatively, this study represents the First neoglycorandomization of a synthetic drug and expands our understanding of the impact of sugar structure upon product distribution/equilibria in the context of N-alkoxyamino-, N-hydroxyamino-, and N-acylhydrazine-based chemoselective glycosylation. This study also revealed several analogues with increased in vitro anticancer activity, most notably D-threoside 60 (NSC 748747), which displayed much broader tumor specificity and notably increased potency over the parent drug.