Microwave-Based Reaction Screening: Tandem Retro-Diels–Alder/Diels–Alder Cycloadditions of o-Quinol Dimers

We have accomplished a parallel screen of cycloaddition partners for o-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels–Alder/Diels–Alder cascades of o-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels–Alder cycloadditions of o-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor.本研究依托微孔板微波反应系统，完成了邻喹诺醇（o-quinol）环加成底物的平行筛选。微波辐照可提升邻喹诺醇二聚体的逆狄尔斯-阿尔德/狄尔斯-阿尔德级联反应效率，该类反应通常以非对映选择性路径进行。计算研究显示，邻喹诺醇参与的狄尔斯-阿尔德环加成反应更倾向于采用非同步过渡态。后续对系列环加合物开展生物学评价，成功筛选得到激活蛋白-1（activator protein-1，AP-1）的抑制剂，该蛋白属于致癌转录因子。