Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Center for Supramolecular Chemistry & Catalysis and Department of Chemistry, College of Science, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China.
J Am Chem Soc. 2021 Feb 10;143(5):2190-2193. doi: 10.1021/jacs.0c12302. Epub 2021 Jan 28.
The traditional end-to-end cyclization of long-chain linear precursors is difficult and often unpredictable because the unfavorable entropy of macrocyclic closure allows undesired intermolecular reactions to compete. Here, we apply cavitands to the selective intramolecular aldol/dehydration reaction of long-chain α,ω-dialdehydes in aqueous solution. Hydrophobic forces drive the dialdehydes into the cavitands in folded conformations and favor macrocyclization reactions over intermolecular reactions observed in bulk solution. The macrocyclic aldol reaction products are isolated in good yields (30-85%) over a wide range (11 to 17-membered rings). Unlike conventional templates that become guests inside their assembled hosts, cavitands reverse the roles and resemble the situation in biological catalysis-the templates are hosts for guests undergoing the assisted reaction processes.
长链线性前体的传统末端到末端的环化反应是困难的，而且往往是不可预测的，因为大环闭合的不利熵允许不希望的分子间反应竞争。在这里，我们在水溶液中应用主体分子来选择性地进行长链α,ω-二醛的分子内羟醛缩合/脱水反应。疏水作用力将二醛驱动进入主体分子的折叠构象中，并有利于环化反应而不是在本体溶液中观察到的分子间反应。在很宽的范围（11 到 17 元环）内，大环羟醛缩合反应产物以良好的收率（30-85%）分离。与在组装的主体中成为客体的常规模板不同，主体分子颠倒了角色，类似于生物催化中的情况-模板是经历辅助反应过程的客体的主体。
