Innocenti Riccardo, Lenci Elena, Menchi Gloria, Trabocchi Andrea
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy.
Interdepartmental Center for Preclinical Development of Molecular Imaging (CISPIM), University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Beilstein J Org Chem. 2020 Feb 12;16:200-211. doi: 10.3762/bjoc.16.23. eCollection 2020.
The Cu-catalyzed multicomponent ketone-amine-alkyne (KA) reaction was combined with a Pauson-Khand cycloaddition to give access of unprecedented constrained spirocyclic pyrrolocyclopentenone derivatives following a DOS couple-pair approach. The polyfunctional molecular scaffolds were tested on the cyclopentenone reactivity to further expand the skeletal diversity, demonstrating the utility of this combined approach in generating novel spiro compounds as starting material for the generation of chemical libraries. The chemoinformatics characterization of the newly-synthesized molecules gave evidence about structural and physicochemical properties with respect to a set of blockbuster drugs, and showed that such scaffolds are drug-like but more spherical and three-dimensional in character than the drugs.
铜催化的多组分酮-胺-炔（KA）反应与Pauson-Khand环加成反应相结合，采用双环氧化合物偶联对方法，得到了前所未有的具有受限结构的螺环吡咯环戊烯酮衍生物。对这些多官能团分子骨架的环戊烯酮反应性进行了测试，以进一步扩大骨架多样性，证明了这种组合方法在生成新型螺环化合物作为化学文库生成起始原料方面的实用性。对新合成分子的化学信息学表征提供了有关其相对于一组畅销药物的结构和物理化学性质的证据，并表明此类骨架具有类药物性质，但比药物更呈球形且具有三维特征。
