在亚提利辛催化下,N-烯二胺胺的分辨率得到了提高
Christopher K Savile1, Vladimir P Magloire, Romas J Kazlauskas
1Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montréal, Québec, H3A 2K6, Canada.
Journal of the American Chemical Society
|February 17, 2005
概括
这项研究引入了第一种生物催化方法,用于生产性硫胺胺,这对于不对称的氨基合成至关重要. 一种特定的酶,subtilisin E,在溶解这些化合物方面表现出高的反选择性,产生了有价值的性辅助剂.
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.
- 酵素工程是什么意思 酵素工程
背景情况:
- 硫胺具有性硫立体中心,使其在不对称合成中成为有价值的性辅助剂.
- 开发高效和enantioselective方法来制备它们对于合成奇拉胺来说至关重要.
研究的目的:
- 建立第一个生物催化路径,用于合成基丰富的硫胺.
- 为了研究硫胺水解中的亚素E的基质范围和酶选择性.
主要方法:
- 使用亚利辛E.E.的各种阿里苏尔菲纳胺的酶性水解.
- 硫胺的格拉姆级分辨率.
- 在 Bacillus subtilis 中过度表达亚素E.
- 分子建模以阐明基质结合和酶选择性决定因素.
主要成果:
- 细素E选择性化N-乙烯和N-二氨基氨基胺,具有高的反选择性 (E > 150).
- 格拉姆尺度的分辨率产生了三个有用的合硫胺辅助剂: (R) -p-toluenesulfinamide (95% ee), (R) -p-chlorobenzenesulfinamide (97% ee) 和 (R) -2,4,6-trimethylbenzenesulfinamide (99% ee). 这三种合硫胺辅助剂的分辨率是: (R) -p-toluenesulfinamide (95% ee), (R) -p-chlorobenzenesulfinamide (97% ee) 和 (R) -2,4,6-trimethylbenzenesulfinamide (99% ee) 的分辨率.
- 分子建模表明,特定的基基模仿氨酸,促进结合,并在S1'口袋驱动器中进行疏水相互作用.
结论:
- 使用亚素E的生物催化剂提供了一种高效且高度选择性的方法,用于获取有价值的性硫胺辅助剂.
- 这些发现为大规模制备这些重要的合成构建块提供了实用途径.
- 分子建模提供了对控制观察到的酶选择活性的酶基质相互作用的见解.
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