(2R,3R,3aR,6S,6aR)-2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butyl-methoxyamino]-3,6-dihydroxy-3,3a,6,6a-tetrahydro-2H-furo[3,2-b]furan-5-one | 1256381-91-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3R,3aR,6S,6aR)-2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butyl-methoxyamino]-3,6-dihydroxy-3,3a,6,6a-tetrahydro-2H-furo[3,2-b]furan-5-one
• CAS: 1256381-91-5
• 化学式: C₂₁H₃₀Cl₂N₂O₆
• 分子量: 477.385
• InChiKey: DWEPJCSKUDCEFD-USYVTKNRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  D-glucurono-6,3-lactone 、 N-methoxy-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 (2R,3R,3aR,6S,6aR)-2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butyl-methoxyamino]-3,6-dihydroxy-3,3a,6,6a-tetrahydro-2H-furo[3,2-b]furan-5-one
  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.