Abstract
<jats:p>The synthesis of pseudo-natural products (PNPs) by combining biosynthetically unrelated fragments provides a powerful strategy for exploring uncharted biological and chemical spaces. Herein, we report the first intermolecular [2+2] cycloaddition between alkenes and benzothiazoles to form an azetidine ring via visible–lightmediated triplet energy transfer delivering a library of diverse PNPs belonging to three frameworks sharing a central penem core. The current method and the resultant PNPs feature chemical potential for further structural diversification. This method with exceptional regio- and diastereoselectivity is practical and scalable. Biological evaluation on this PNP library (85 compounds) led to the identification of a big number of non-cytotoxic inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) that over express associated with many fatal diseases, and delineated their structure–activity relationships (SAR). Mechanism study on the representative compound 40 (IC50 = 3.58 μM) indicated that it acts as a competitive apo-IDO1 inhibitor by occupying the hemebinding pocket.</jats:p>