硫酸介导的原子插入用于N-异环的后期骨架编辑
Bidhan Ghosh1, Prakash Kafle1, Rishav Mukherjee1
1Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, OK, USA.
研究人员开发了一种新方法,将单个原子插入异环化合物中,为药物发现创造多样化的分子支架. 这种高效的骨编辑技术使用硫酸扩大了化学多样性.
科学领域:
- 有机化学
- 医学化学
- 合成化学
背景情况:
- 在许多商业药物中,含的异环是关键的支架.
- 提高药物发现图书馆的化学多样性对于发现新疗法至关重要.
- 通过结合原子来跳跃脚手架是一个有前途的策略.
研究的目的:
- 开发一种选择性方法,将单个原子纳入易于获得的异环化合物中.
- 分别将pyrroles,indols和imidazoles转化为合成具有挑战性的pyrimidines,quinazolines和triazines.
- 扩大药物发现图书馆的化学多样性.
主要方法:
- 使用硫酸的独特反应性来插入原子.
- 使用没有添加剂的,稳定的硫烯前体.
- 在广泛的温度范围 (-30~150°C) 上应用该方法.
- 进行机械学研究和密度函数理论 (DFT) 计算.
主要成果:
- 已成功地将醇,醇和醇转化为胺,醇和酸.
- 与多种功能组相容,包括对氧化敏感的功能组 (,).
- 这种方法适用于天然产品,氨基酸和药品.
- 通过DFT计算探索区域选择性结果.
结论:
- 硫酸介导的骨架编辑提供了一个有效的途径,以新含有异环.
- 这种无添加剂的方法增强了药物发现库中的化学多样性.
- 这种方法是多功能,强大,适用于复杂的分子.
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