马克萨米辛的不同总合成和特征
Journal of the American Chemical Society
|June 6, 2023
概括
一种名为maxamycins的新型合成万科米辛类药物提供了有效的抗菌剂,对抗性细菌有效. 这些新药在体内显示出对MRSA和VRSA等具有挑战性的菌株的有效性.
科学领域:
- 医学化学
- 有机合成
- 发现抗菌药物
背景情况:
- 但抗药性是一个日益增长的威胁.
- 开发新的万科米辛类似物对于对抗抗性格拉姆阳性感染至关重要.
- 目前存在的合成途径往往很长,产量也很低.
研究的目的:
- 开发一种简化和可扩展的口袋修饰的万科米辛类似物.
- 创建一个共同的中间体,用于各种范素模拟的修饰.
- 合成和评估具有增强抗菌性能的新型maxamycins.
主要方法:
- 一种不同的总合成方法,产生一种常见的后期中间体,[Ψ[C(S) NH]Tpg4]vancomycin.
- 亚格利康的选择性合成和一个的酶糖化.
- 胺基转化为胺基/氨基甲基的后期转化,并结合了外围的修改.
主要成果:
- 一个可扩展的合成 (18个步骤,12%的产量,>5g) 的关键中间体,使其能够获得多种类型的类似物.
- 成功合成具有强大,持久和有效的抗菌活性的新型胺基最大菌素.
- 具有三种协同作用机制,对温素敏感和耐药的格拉姆阳性生物具有均效作用.
结论:
- 开发的合成策略为新型万科米辛和马克萨米辛类似物提供了广泛的获取机会.
- 新型基于阿米丁的maxamycins显示出作为下一代抗生素的巨大潜力.
- 一种maxamycin类似物 (MX- 4) 在体内对具有挑战性的MRSA和VRSA菌株显示出有希望的疗效.
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