Department of Organic Chemistry, Faculty of Science, Palacky University, 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Center, University of Notre Dame, Notre Dame, IN 46556, USA.
Molecules. 2018 May 4;23(5):1090. doi: 10.3390/molecules23051090.
We report two synthetic strategies for traceless solid-phase synthesis of molecular scaffolds comprising 6- to 8-membered rings fused with 5- to 7-membered rings. Traceless synthesis facilitated preparation of target molecules without any trace of polymer-supported linkers. The cyclization proceeded via acid-mediated tandem -acylium ion formation followed by the nucleophilic addition of - and -nucleophiles. The presented synthetic strategy enabled, through the use of simple building blocks without any conformational preferences, the evaluation of the predisposition of different combinations of ring sizes to form fused ring molecular scaffolds. Compounds with any combination of [6,7 + 5,6,7] ring sizes were accessible with excellent crude purity. The 8-membered cyclic iminium was successfully fused only with the 5-membered cycle and larger fused ring systems were not formed, probably due to their instability.
我们报告了两种无痕迹固相合成包含 6 至 8 元环与 5 至 7 元环稠合的分子支架的策略。无痕迹合成有助于制备没有任何聚合物支持连接物痕迹的目标分子。环化通过酸介导的串联 -acylium 离子形成，然后进行 - 和 - 亲核试剂的亲核加成。所提出的合成策略通过使用没有任何构象偏好的简单构建块，评估了不同大小的环组合形成稠合环分子支架的倾向性。具有任何 [6,7 + 5,6,7] 环大小组合的化合物都可以通过使用简单的构建块来获得，并且具有出色的粗纯度。8 元环状亚氨基仅成功地与 5 元环稠合，并且没有形成更大的稠合环系统，这可能是由于它们的不稳定性。
