Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université Paris Descartes, PRES Sorbonne Paris Cité, 45 rue des Saints Pères, 75006 Paris, France.
Chemistry. 2013 Jan 7;19(2):642-53. doi: 10.1002/chem.201202391. Epub 2012 Nov 20.
A biomimetic strategy for the monofunctionalization of a calix[6]arene core is described. It is based on host-guest chemistry (mimicking the Michaelis-Menten adduct in enzymes) and allows the finely tuned pre-organization of the substrate (an alkyne) with respect to the reactant (three azido groups introduced at the calixarene large rim). It is shown that the thermal Huisgen reaction implemented in this work proceeds under very mild conditions with total regioselectivity of the cycloaddition process. The scope of the reaction was explored and the results suggest that such a supramolecular strategy is quite versatile and could be applied to the selective functionalization of other cavitands bearing different recognition patterns. A detailed structural, thermodynamic, and kinetic study is also reported, highlighting interesting biomimetic features: The importance of the host-guest adduct strength, the high sensitivity of the reaction to the pre-organization of the reactive partners (alkyne vs. azide), and a significant impact of the embedment on the transition state. The self-coordination of the monofunctionalized products was also studied and an "endo/exo" switch of the internal side-chain could be triggered by adding competitive ligands.
描述了一种杯[6]芳烃核单官能化的仿生策略。它基于主客体化学（模拟酶中的米氏酶加合物），允许对底物（炔烃）相对于反应物（在杯芳烃大边缘引入的三个叠氮基团）进行精细的预组织。结果表明，在这项工作中实施的热 Huisgen 反应在非常温和的条件下进行，环加成过程具有完全的区域选择性。还探索了反应的范围，结果表明这种超分子策略非常通用，可以应用于其他带有不同识别模式的穴状配体的选择性官能化。还报道了详细的结构、热力学和动力学研究，突出了有趣的仿生特征：主客体加合物强度的重要性、反应对反应伙伴（炔烃与叠氮化物）预组织的高度敏感性，以及嵌入对过渡态的显著影响。还研究了单官能化产物的自配位，通过添加竞争配体可以触发内部侧链的“内/外”开关。
