基质选择性催化启用了阿扎菲隆天然产品的合成
Ye Wang1, Katherine J Torma1, Joshua B Pyser1
1Life Sciences Institute, Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS central science
|April 1, 2024
概括
这项研究使用酶基质选择性来控制化学反应,合成了五种新的阿扎菲龙天然产品和衍生物. 这种仿生方法可以精确合成复杂分子.
科学领域:
- 有机化学 有机化学
- 生物催化剂是一种生物催化剂.
- 自然产品的合成自然产品的合成
背景情况:
- 大自然在合成中使用催化剂来控制反应,实现了高基质选择性.
- 在实验室环境中模仿大自然的催化选择性存在重大挑战.
- 阿扎菲隆天然产品具有线性和角三环核,其子集在自然中发现.
研究的目的:
- 利用基质选择性催化来控制阿扎菲隆天然产品的合成.
- 以指导中间体的循环向特定的线性或角三循环核心.
- 开发一种简化合成策略,使用序列酶反应来合成阿扎菲隆.
主要方法:
- 使用了一种依赖于黄素的单氧化酶 (FDMO) 与一种转移酶 (AT) 序列.
- 采用基质选择性催化,以在平衡状态下区分中间体.
- 进行了机理学研究,以了解基质平衡和酶选择性的作用.
主要成果:
- 首次成功合成了五种阿扎菲龙天然产品.
- 产生了几种非自然的阿扎菲龙衍生物.
- 在一个中,证明了甲基底的直接转化为线性三环亚扎菲隆.
结论:
- 酶基质选择性对于控制线性与角三循环阿扎菲隆的形成至关重要.
- 一个顺序的酶策略使复杂的天然产品能够有效合成.
- 这种方法为访问阿扎菲龙支架及其类型提供了一种强大的方法.
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