化学酶总合成-氧化:第二,第三和第四代策略
Mariia Makarova1, Mary Ann A Endoma-Arias1, Helen E Dela Paz1
1Department of Chemistry and Centre for Biotechnology , Brock University , 1812 Sir Isaac Brock Way , St. Catharines , Ontario L2S 3A1 , Canada.
Journal of the American Chemical Society
|June 12, 2019
概括
使用生物衍生原料开发了四种新合成途径. 这些策略展示了阿片类类似物化学合成的进步.
科学领域:
- 有机化学
- 合成化学
- 生物技术
背景情况:
- 片合成面临着复杂的挑战.
- 开发有效的阿片类同类药物对研究至关重要.
- 有机原料提供了可持续的途径.
研究的目的:
- 设计并完成四种不同的氧合成.
- 探索和比较不同的合成策略来构建氧核.
- 使用由工程化大肠杆菌制造的生物衍生中间产物.
主要方法:
- 使用大肠杆菌JM109 (pDTG601A) 进行全细胞发酵,产生关键的二烯二醇中间体.
- 应用SmI2介导的循环化,亨利反应,亚酸-乳酸盐形成,以及酸-酸降解合用于C-9/C-14键构造.
- 在早期合成中利用帕克的循环形成.
主要成果:
- 通过四种不同的世代方法成功合成了氧.
- 第四代合成是最有效的,完成了11个操作 (18个步骤).
- 每一代人表现出关键的结合形式和环形结构的独特策略.
结论:
- 该研究介绍了合成策略向氧的进展,强调了效率的提高.
- 生物发酵原料的使用证明了可持续的方法.
- 提供了所有新化合物的详细实验和光谱数据,以促进进一步的研究.
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