基拉酸脱酶抑制剂的单合成和抗真菌活性研究
Donghua Du1, Yu Chen2, Chengbing Yang1
1College of Chemistry, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
概括
新型性酸脱酶抑制剂 (SDHI) 通过Rh催化方法合成. 这些化合物表现出强烈的抗真菌活性,在异构体之间存在显著差异,特别是在Botrytis cinerea.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 酸脱酶抑制剂 (SDHI) 在农业和医学中至关重要.
- 开发具有高疗效和立体选择性的新型性SDHI是一个持续的挑战.
- 了解生物活性中的等离子体差异是有针对性的应用的关键.
研究的目的:
- 开发一种高效和立体选择性的新型合性SDHI的合成.
- 研究这些SDHI及其反体的抗真菌活性.
- 为了阐明分子层面的抑制机制.
主要方法:
- 一Rh催化不对称化-凝结用于SDHI合成.
- 广泛的基质范围评估 (68个例子).
- 在体外和体外抗真菌试验,分子对接,分子动力学和酶活性试验.
主要成果:
- 实现了高效率 (高达1000,产量94%) 和立体选择性 (高达99% ee).
- 对于合成的SDHI,已证明具有广泛的和强大的抗真菌活性.
- (S) 解体表现出比 (R) 解体显著更高的抗真菌活性,例如对Botrytis cinerea (EC50 = 0.48μm对比36.7μm).
- (S) - 5f 显示了比其R enantiomer更有效地抑制了糖酸脱酶.
结论:
- 开发的Rh催化策略为合成性SDHI提供了一条优越的途径.
- SDHIs 的反体表现出不同的生物活动和作用机制.
- 这些发现为开发更有效和选择性的抗真菌剂铺平了道路.
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