压力释放异原子功能化:发展,范围和立体特异性
Justin M Lopchuk1, Kasper Fjelbye1, Yu Kawamata1
1Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|February 1, 2017
概括
药物化学家现在可以很容易地在药物发现中安装像bicyclo[1.1.1]pentane这样的应变环,使用一种新的应变释放策略. 这种方法允许"任何阶段"的功能化,简化复杂分子的合成.
科学领域:
- 有机化学
- 医学化学
- 药物发现
背景情况:
- 药物发现越来越多地利用压力生物异构剂 (例如,双环[1.1.1],亚丁,循环) 来探索新的化学空间.
- 合并这些压缩碎片的合成挑战往往阻碍了它们在化合物修饰中的应用.
研究的目的:
- 开发一个简单的"任何阶段"安装小,紧张的环系统的总体策略.
- 引入一种新型立体特异性应变释放反应,以功能化带有应变环的异质原子.
主要方法:
- 使用与核友反应的弹载荷C-C和C-N键的一般策略的开发.
- 该方法应用于小型构建块,后期中间体,生物结合和标签.
- 合成和表征四种新的性"cyclopentylation"试剂.
主要成果:
- 证明了"任何阶段"的紧张环的安装,克服了以前的合成障碍.
- 首次实现了氨基,醇,硫醇和碳酸的立体特异性应变释放功能.
- 成功地将该方法应用于生物结合和标签.
结论:
- 开发的应变释放策略为药物化学中纳入应变环提供了一种多功能且有效的方法.
- 这种方法显著扩大了用于药物发现和化学生物学应用的合成异构体的可用性.
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