benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-[[methyl-(4-methylphenyl)sulfonylamino]sulfanylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 805231-40-7

• 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: benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-[[methyl-(4-methylphenyl)sulfonylamino]sulfanylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 805231-40-7
• 化学式: C₃₁H₃₁N₃O₇S₃
• 分子量: 653.801
• InChiKey: BSGUNAFQEACOKU-PDDLMNHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  181
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-[[methyl-(4-methylphenyl)sulfonylamino]sulfanylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 在 magnesium bromide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.5h， 以76%的产率得到benzhydryl (6R,7Z)-3-(acetyloxymethyl)-7-[methyl-(4-methylphenyl)sulfonylamino]sulfanylimino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT

  摘要：

  In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the T-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-ammosulfenimine following its incorporation.

  DOI：

  10.1021/jo048970i
• 作为产物：
  描述：

  二苯基重氮甲烷 以 二氯甲烷 、 氯仿 为溶剂， 反应 72.0h， 生成 benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-[[methyl-(4-methylphenyl)sulfonylamino]sulfanylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT

  摘要：

  In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the T-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-ammosulfenimine following its incorporation.

  DOI：

  10.1021/jo048970i

文献信息

• Toward the Development of a Cephalosporin-Based Dual-Release Prodrug for Use in ADEPT
  作者：Jonathan W. Grant、Timothy P. Smyth

  DOI：10.1021/jo048970i

  日期：2004.11.1

  In previous work we have shown that a cephalosporin structure bearing an S-aminosulfenimine at the 7-position behaved as a beta-lactamase-dependent dual-release prodrug. Scission of the beta-lactam ring of such a structure led to the rapid loss of the sulfur-attached side chain moiety via an intramolecular displacement, while the T-group was lost via the well-established elimination process at that position. In the present work we report on an evaluation of the scope and limitations of exploiting the S-aminosulfenimine functionality to generate a cephalosporin-based prodrug incorporating two biologically active components. Starting from 7-ACA, a viable synthetic cycle was put in place that avoided formation of the Delta(2) isomer throughout and that allowed incorporation of aminoglutethimide at the 3'-position and of a tosyl S-aminosulfenimine at the 7-position. The direct incorporation of a biologically active sulfonamide (ethoxzolamide) or a sulfamate (coumate) at this latter position was not achieved as a result of the difficulty of generating the corresponding sulfur diimides. An indirect route for the formation of an S-aminosulfenimine was put in place, as was a general method of alkylation (Mitsunobu reaction) of the tosyl S-ammosulfenimine following its incorporation.