tert-butyl 7α-methoxy-3-methyl-3-cephem-4-thiolcarboxylate 1,1-dioxide | 148115-09-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 7α-methoxy-3-methyl-3-cephem-4-thiolcarboxylate 1,1-dioxide
• 英文别名: (6R,7S)-7-methoxy-3-methyl-5,5,8-trioxo-5-thia-1-aza-bicyclo[ 4.2.0]oct-2-ene-2-carbothioic acid S-tert-butyl ester；(6R,7S)-7-methoxy-3-methyl-5,5,8-trioxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbothioic acid S-tert-butyl ester；(6R,7S)-7-methoxy-3-methyl-5,5,8-trioxo-5-thia-1aza-bicyclo[4.2.0]oct-2-ene-2-carbothioic acid S-tert-butyl ester；S-tert-butyl (6R,7S)-7-methoxy-3-methyl-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioate
• CAS: 148115-09-7
• 化学式: C₁₃H₁₉NO₅S₂
• 分子量: 333.43
• InChiKey: QYEDILCUCKBCBN-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,5-二氮杂双环[4.3.0]壬-5-烯 、 tert-butyl 7α-methoxy-3-methyl-3-cephem-4-thiolcarboxylate 1,1-dioxide 在 过氧化苯甲酰 作用下， 以 乙腈 为溶剂， 生成 Benzoic Acid (6R,7S)-2-tert-butylsulfanylcarbonyl-7-methoxy-3-methyl-5,5,8-trioxo-5-thia-1-aza-bicyclo [4.2.0]oct-2-en-4-yl Ester
  参考文献：
  名称：

  4-SUBSTITUTED CEPHEM DERIVATIVES AS ELASTASE INHIBITORS

  摘要：

  本发明涉及头孢烯衍生物及其制备方法，该衍生物在C-2位具有适当的取代基，即杂环硫基或酰氧基。它们是强效的蛋白酶抑制剂，特别是人白细胞弹性蛋白酶（HLE）抑制剂。这些抑制剂可以通过从已知的头孢烯化合物开始，通过取代反应合成，该化合物在2位具有合适的离去基团。

  公开号：

  US20010011085A1
• 作为产物：
  描述：

  (6R,7S)-7-methoxy-3-methyl-5,5,8-trioxo-5lambda6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 、 叔丁基硫醇 在 吡啶 、 H-pEEDSG-OH 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以73%的产率得到tert-butyl 7α-methoxy-3-methyl-3-cephem-4-thiolcarboxylate 1,1-dioxide
  参考文献：
  名称：

  Synthesis and evaluation of new elastase inhibitors. I. 1,1-Dioxocephem-4-thiolesters

  摘要：

  Several 7alpha-chloro and 7alpha-methoxy cephalosporin thiolester sulphones variously substituted at the C-3' position were synthesized from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA). The compounds are time-dependent inhibitors of human leukocyte elastase (HLE) with effective K(i) ranging from micro- to nanomolar values, and second order rate constant reaching 10(6) M-1s-1; they also inhibit porcine pancreatic elastase with similar, though not identical efficiency. Compared to the corresponding cephem esters, the thiolesters of the 7-Cl series inhibit HLE up to 10 times as fast. Complete enzyme inactivation is achieved when a leaving group at C-3' (OAc or S-Het) is present, at the expense however of stability towards hydrolytic beta-lactam cleavage. In the 7-OMe series the thiolester compounds are far more stable and retain good efficiency for irreversible enzyme inhibition, superior to that displayed by the corresponding ester compounds. Three representative compounds (including one ester and two thiolesters) are shown to be effective inhibitors of HLE in the presence of insoluble elastin.

  DOI：

  10.1016/0223-5234(92)90019-w