S-sec-butyl methanethiosulfonate

• 分子结构分类: 有机化合物 - 有机硫化合物 - 磺酰类
• 英文名称: S-sec-butyl methanethiosulfonate
• 英文别名: 2-Methylsulfonylsulfanylbutane
• 化学式: C₅H₁₂O₂S₂
• 分子量: 168.281
• InChiKey: MCJISRFQTZWGDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  67.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  coenzyme A trilithium salt 、 S-sec-butyl methanethiosulfonate 以 甲醇 为溶剂， 反应 0.5h， 以95%的产率得到
  参考文献：
  名称：

  N-thiolated β-lactams: Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus

  摘要：

  This study focuses on the mechanism of action of N-alkylthio beta-lactains, a new family of antibacterial compounds that show promising activity against Staphylococcus and Bacillus microbes. Previous investigations have determined that these compounds are highly selective towards these bacteria, and possess completely unprecedented structure-activity profiles for a beta-lactam antibiotic. Unlike penicillin, which inhibits cell wall crosslinking proteins and affords a broad spectrum of bacteriocidal activity, these N-thiolated lactams are bacteriostatic in their behavior and act through a different mechanistic mode. Our current findings indicate that the compounds react rapidly within the bacterial cell with coenzyme A (CoA) through in vivo transfer of the N-thio group to produce an alkyl-CoA mixed disulfide species, which then interferes with fatty acid biosynthesis. Our studies on coenzyme A disulfide reductase show that the CoA thiol-redox buffer is not perturbed by these compounds; however, the lactams appear to act as prodrugs. The experimental evidence that these beta-lactams inhibit fatty acid biosynthesis in bacteria, and the elucidation of coenzyme A as a primary cellular target, offers opportunities for the discovery of other small organic compounds that can be developed as therapeutics for MRSA and anthrax infections. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.027
• 作为产物：
  描述：

  二仲丁基二硫醚 、 硫甲磺酸钠 在 碘 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以70%的产率得到S-sec-butyl methanethiosulfonate
  参考文献：
  名称：

  N-thiolated β-lactams: Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus

  摘要：

  This study focuses on the mechanism of action of N-alkylthio beta-lactains, a new family of antibacterial compounds that show promising activity against Staphylococcus and Bacillus microbes. Previous investigations have determined that these compounds are highly selective towards these bacteria, and possess completely unprecedented structure-activity profiles for a beta-lactam antibiotic. Unlike penicillin, which inhibits cell wall crosslinking proteins and affords a broad spectrum of bacteriocidal activity, these N-thiolated lactams are bacteriostatic in their behavior and act through a different mechanistic mode. Our current findings indicate that the compounds react rapidly within the bacterial cell with coenzyme A (CoA) through in vivo transfer of the N-thio group to produce an alkyl-CoA mixed disulfide species, which then interferes with fatty acid biosynthesis. Our studies on coenzyme A disulfide reductase show that the CoA thiol-redox buffer is not perturbed by these compounds; however, the lactams appear to act as prodrugs. The experimental evidence that these beta-lactams inhibit fatty acid biosynthesis in bacteria, and the elucidation of coenzyme A as a primary cellular target, offers opportunities for the discovery of other small organic compounds that can be developed as therapeutics for MRSA and anthrax infections. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.027

文献信息

• N-alkylthio beta-lactams, alkyl-coenzyme a asymmetric disulfides, and aryl-alkyl disulfides as anti-bacterial agents
  申请人：Turos Edward

  公开号：US20080182815A1

  公开（公告）日：2008-07-31

  The present invention provides N-alkylthio β-lactams and disulfide compounds (e.g., alkyl-coenzyme A asymmetric disulfides or aryl-alkyl disulfides), compositions containing such compounds, and method of their use as anti-bacterial agents.

  本发明提供了N-烷基硫代β-内酰胺和二硫化合物（例如，烷基辅酶A不对称二硫化合物或芳基-烷基二硫化合物），含有这些化合物的组合物，以及将它们用作抗菌剂的方法。
• Unsymmetric aryl–alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis
  作者：Edward Turos、Kevin D. Revell、Praveen Ramaraju、Danielle A. Gergeres、Kerriann Greenhalgh、Ashley Young、Nalini Sathyanarayan、Sonja Dickey、Daniel Lim、Mamoun M. Alhamadsheh

  DOI：10.1016/j.bmc.2008.05.032

  日期：2008.7.1

  attack on the disulfide bond. Small alkyl residues on the other sulfur provide the best activity as well, which for different bacteria appears to be somewhat dependent on the nature of the alkyl moiety. The mechanism of action of these lipophilic disulfides is likely similar to that of previously reported N-thiolated beta-lactams, which have been shown to produce alkyl-CoA disulfides through a thiol-disulfide

  本研究描述了合成生产的混合芳烷基二硫化物化合物的抗菌特性，作为控制金黄色葡萄球菌和炭疽芽孢杆菌生长的一种手段。其中一些化合物具有很强的体外生物活性。我们的结果表明，在检查的 12 种不同的芳基取代基中，硝基苯基衍生物提供最强的抗生素活性。这可能是芳硫基部分作为离去基团对二硫键进行亲核攻击的电子活化的结果。其他硫上的小烷基残基也提供最佳活性，对于不同的细菌，这似乎在某种程度上取决于烷基部分的性质。这些亲脂性二硫化物的作用机制可能与之前报道的 N-硫醇化 β-内酰胺相似，已显示通过细胞质内的硫醇-二硫化物交换产生烷基-CoA 二硫化物，最终抑制 II 型脂肪酸合成。然而，混合的烷基辅酶 A 二硫化物本身没有抗菌活性，可能是由于高极性化合物不能穿过细菌细胞膜。已发现这些结构简单的二硫化物可抑制 β-酮酰基-酰基载体蛋白合酶 III 或 FabH（II 型脂肪酸生物合成中的关键酶），因此可作为开发针对
• N-thiolated β-lactams: Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus
  作者：Kevin D. Revell、Bart Heldreth、Timothy E. Long、Seyoung Jang、Edward Turos

  DOI：10.1016/j.bmc.2006.12.027

  日期：2007.3

  This study focuses on the mechanism of action of N-alkylthio beta-lactains, a new family of antibacterial compounds that show promising activity against Staphylococcus and Bacillus microbes. Previous investigations have determined that these compounds are highly selective towards these bacteria, and possess completely unprecedented structure-activity profiles for a beta-lactam antibiotic. Unlike penicillin, which inhibits cell wall crosslinking proteins and affords a broad spectrum of bacteriocidal activity, these N-thiolated lactams are bacteriostatic in their behavior and act through a different mechanistic mode. Our current findings indicate that the compounds react rapidly within the bacterial cell with coenzyme A (CoA) through in vivo transfer of the N-thio group to produce an alkyl-CoA mixed disulfide species, which then interferes with fatty acid biosynthesis. Our studies on coenzyme A disulfide reductase show that the CoA thiol-redox buffer is not perturbed by these compounds; however, the lactams appear to act as prodrugs. The experimental evidence that these beta-lactams inhibit fatty acid biosynthesis in bacteria, and the elucidation of coenzyme A as a primary cellular target, offers opportunities for the discovery of other small organic compounds that can be developed as therapeutics for MRSA and anthrax infections. (c) 2006 Elsevier Ltd. All rights reserved.