N-(4-methyl-3-chlorophenyl) O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate | 184579-76-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-methyl-3-chlorophenyl) O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate
• 英文别名: methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[(3-chloro-4-methylphenyl)carbamoyloxy]oxane-2-carboxylate
• CAS: 184579-76-8
• 化学式: C₂₁H₂₄ClNO₁₁
• 分子量: 501.875
• InChiKey: MNUROOHYKLHGBE-CBNQQXHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  153
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(4-methyl-3-chlorophenyl) O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 水 、 silver nitrate 、 N,N-二异丙基乙胺 作用下， 以 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 50.5h， 生成 N-[4-(daunorubicin-N-carbonyloxymethyl)-3-chlorophenyl] O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate
  参考文献：
  名称：

  Novel anthracycline-spacer-β-glucuronide, -β-glucoside, and -β-galactoside prodrugs for application in selective chemotherapy

  摘要：

  A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-beta-glycoside were designed to be activated by beta-glucuronidase or beta-galactosidase. Prodrugs with -chloro, bromo or -n-hexyl substituents on the spacer were synthesized as well as prodrugs containing a -beta-glucuronyl, -beta-glucosyl or -beta-galactosyl carbamate specifier. The key step in the synthesis of all prodrugs is the highly beta-diastereoselective addition reaction of the anomeric hydroxyl of a glycosyl donor to a spacer isocyanate resulting in the respective beta-glycosyl carbamate pro-moieties. The resulting protected pro-moieties were coupled to an anthracycline. Prodrugs were evaluated with respect to activation rate by the appropriate enzyme and additionally, their IC50 values were determined. Optimal prodrugs in this study were at least 100- to 200-fold less toxic than their corresponding drug in vitro and were activated to the parent drug in a half-life time of approximately 2 h. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00095-4
• 作为产物：
  描述：

  methyl 2,3,4-tri-O-acetyl-D-glucopyranuronate 、 3-氯-4-甲基苯基异氰酸酯 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以80%的产率得到N-(4-methyl-3-chlorophenyl) O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate
  参考文献：
  名称：

  Highly Diastereoselective Synthesis of Anomeric β-O-Glycopyranosyl Carbamates from Isocyanates

  摘要：

  1-β-O-Glycopyranosyl carbamates 是通过在几乎 100% β-对映选择性下，从无保护的α-糖苷和异氰酸酯制备的。异氰酸酯则是由羧酸通过酰基叠氮化物原位制备得来的。

  DOI：

  10.1055/s-1996-4377