生物催化合成的甲素及其类似物
Zhu-Xiang Wang1, Hong-Kang Fu1, Xin-Yu Da1
1Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563006, P. R. China.
Organic letters
|July 5, 2023
概括
一种新的生物催化方法使用氨酸脱酶合成甲素和类似物. 蛋白质工程取得了高和血甲松的产量,使相关化合物的高效合成成为可能.
科学领域:
- 生物催化剂是一种生物催化剂.
- 酶合成酶的合成
- 药用化学 医学化学
背景情况:
- 梅塔克萨隆是一种肌肉松剂.
- 对于药物发现而言,高效合成甲素及其类似物是很重要的.
- 氨酸脱酶 (HHDH) 是一种具有生物催化应用潜力的酶.
研究的目的:
- 开发一种生物催化方法来合成甲素及其类似物.
- 为了改进氨酸脱酶,以提高催化活性和选择性.
- 为了实现基拉和赛米甲萨和类似物的克拉尺度合成.
主要方法:
- 使用环氧化物和酸盐的生物催化合成.
- 由氨酸脱原酶 (HHDH) 进行酶催化.
- 来自Acidimicrobiia细菌*的HHDHamb的蛋白质工程.
主要成果:
- 在克拉尺度上合成甲沙龙,获得了44%的产量 (98% ee) 对于奇拉形式和81%的产量对于赛血形式.
- 合成各种甲素类似物,其合性形式的产量为28-40% (90-99% ee),种族性形式的产量为77-92%.
- 在生物催化合成中证明了工程HHDH的有效性.
结论:
- 建立了一个强大的生物催化方法来合成甲素和类似物.
- HHDH的蛋白质工程显著提高了合成效率和酶选择性.
- 这种方法提供了一种可持续和有效的生产合性和血性metaxalone衍生物的途径.
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