S-phenyl (2Z)-2-[(3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-ylidene]ethanethioate | 608535-33-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯硫酚酯
• 英文名称: S-phenyl (2Z)-2-[(3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-ylidene]ethanethioate
• CAS: 608535-33-7
• 化学式: C₁₉H₂₇NO₃SSi
• 分子量: 377.58
• InChiKey: DWMPNCPXQARGKK-FVGVYWHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯-2-氧代乙酸苄酯 、 S-phenyl (2Z)-2-[(3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-ylidene]ethanethioate 以 苯 为溶剂， 以89%的产率得到benzyl 2-[(3S,4Z)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-2-oxo-4-(2-oxo-2-phenylsulfanylethylidene)azetidin-1-yl]-2-oxoacetate
  参考文献：
  名称：

  N -4-亚烷基-β-内酰胺的酰化作用：出乎意料的结果

  摘要：

  本文描述了碱性条件下E-和Z -4-亚烷基-β-内酰胺在酰化反应中的不同反应性。该ë异构体很容易酰化，而ž反应的缓慢重排以相应的恶嗪-6-酮。用苯中的草酰氯或丙二酰氯在回流下成功获得Z异构体的N-酰化。

  DOI：

  10.1016/s0040-4039(03)01533-8
• 作为产物：
  描述：

  4-乙酰氧基氮杂环丁酮 在 四氯化钛 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 S-phenyl (2Z)-2-[(3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-ylidene]ethanethioate
  参考文献：
  名称：

  4-Alkylidene-azetidin-2-ones: novel inhibitors of leukocyte elastase and gelatinase

  摘要：

  In addition to their antibiotic potency, beta-lactams have recently been investigated as inhibitors of serine proteinase such as leukocyte elastase (LE), released by inflammatory cells. We describe the synthesis of a series of 4-alkylidene-beta-lactams, and investigate how substitutions on C-3, C-4, and N-1 of the beta-lactam ring affect the activity of human LE and gelatinases MMP-2 and MMP-9. LE activity was measured using a chromogenic substrate, while gelatin-zymography assay was used to evaluate gelatinase activity. We demonstrate that C-4 unsaturation on the beta-lactam ring determines the degree of biological activity, with a selectivity over LE by 3[1-(tert-butyldimethylsilytoxy)-ethyl] derivatives (lowest IC50 was 4muM), and over gelatinase MMP-2 by C-3-unsubstituted 4-[1-ethoxycarbonyl]-ethylidene-beta-lactams (lowest IC50 was 60 muM). (3S)-3-[(IR)-1-hydroxyethyl]-4-(1-etboxycarbonyl)-ethylidene-azetidin-2-one inhibits gelatinase MMP-9. The compounds tested showed no cytotoxicity against NIH-3T3 murine fibroblasts. This is the first example of beta-lactams inhibiting metallo-proteinases instrumental in cancer invasion and angiogenesis. These molecules are good candidates for prototype drugs showing selective antibiotic, anti-inflammatory, and anti-invasion properties. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.035

文献信息

• N-Acylation of 4-alkylidene-β-lactams: unexpected results
  作者：Gianfranco Cainelli、Daria Giacomini、Massimo Gazzano、Paola Galletti、Arianna Quintavalla

  DOI：10.1016/s0040-4039(03)01533-8

  日期：2003.8

  This paper describes the different reactivity of E- and Z-4-alkylidene-β-lactams in acylation reactions under basic conditions. The E isomer is readily acylated, whereas the Z reacted sluggishly rearranging to the corresponding oxazin-6-one. The N-acylation of Z isomers was successfully obtained with oxalyl- or malonyl chlorides in benzene at reflux.

  本文描述了碱性条件下E-和Z -4-亚烷基-β-内酰胺在酰化反应中的不同反应性。该ë异构体很容易酰化，而ž反应的缓慢重排以相应的恶嗪-6-酮。用苯中的草酰氯或丙二酰氯在回流下成功获得Z异构体的N-酰化。
• 4-Alkylidene-azetidin-2-ones: novel inhibitors of leukocyte elastase and gelatinase
  作者：Gianfranco Cainelli、Paola Galletti、Spiridione Garbisa、Daria Giacomini、Luigi Sartor、Arianna Quintavalla

  DOI：10.1016/j.bmc.2003.09.035

  日期：2003.12

  In addition to their antibiotic potency, beta-lactams have recently been investigated as inhibitors of serine proteinase such as leukocyte elastase (LE), released by inflammatory cells. We describe the synthesis of a series of 4-alkylidene-beta-lactams, and investigate how substitutions on C-3, C-4, and N-1 of the beta-lactam ring affect the activity of human LE and gelatinases MMP-2 and MMP-9. LE activity was measured using a chromogenic substrate, while gelatin-zymography assay was used to evaluate gelatinase activity. We demonstrate that C-4 unsaturation on the beta-lactam ring determines the degree of biological activity, with a selectivity over LE by 3[1-(tert-butyldimethylsilytoxy)-ethyl] derivatives (lowest IC50 was 4muM), and over gelatinase MMP-2 by C-3-unsubstituted 4-[1-ethoxycarbonyl]-ethylidene-beta-lactams (lowest IC50 was 60 muM). (3S)-3-[(IR)-1-hydroxyethyl]-4-(1-etboxycarbonyl)-ethylidene-azetidin-2-one inhibits gelatinase MMP-9. The compounds tested showed no cytotoxicity against NIH-3T3 murine fibroblasts. This is the first example of beta-lactams inhibiting metallo-proteinases instrumental in cancer invasion and angiogenesis. These molecules are good candidates for prototype drugs showing selective antibiotic, anti-inflammatory, and anti-invasion properties. (C) 2003 Elsevier Ltd. All rights reserved.