A Pyrene-Linked Cavity within a beta-Barrel Protein Promotes an Asymmetric Diels-Alder Reaction

摘要

A unique pi-expanded reaction cavity tethering a polycyclic moiety which provides a platform for substrate binding was constructed within the robust beta-barrel structure of nitrobindin (NB). NB variants with cavities of different sizes and shapes are coupled with N-(1-pyrenyl)maleimide (Pyr) to prepare a series of NB-Pyr conjugates. The orientation of the pyrene moiety is fixed within the cavity by the coupling reaction. The fluorescent quenching analysis of NB-Pyr indicates that azachalcone (aza), which is a dienophile for a Diels-Alder (DA) reaction, is efficiently incorporated within the pyrene-linked reaction cavity by the aromatic interaction. The DA reaction between aza and cyclopentadiene proceeds within the reaction cavity of NB-Pyr in the presence of Cu-II ion in high yield and high enantio-and regioselectivity.