Stereoselective Total Synthesis of Bisorbicillinoid Natural Products by Enzymatic Oxidative Dearomatization/Dimerization

Natural products are a virtually inexhaustible source of small molecules with spectacular molecular architectures and biomedical potential. Their structural complexity generates formidable challenges to total synthesis but often also precludes time- and resource-efficient, stereoselective synthetic access. Biosynthetically, nature frequently uses dimerization and oligomerization reactions to produce highly challenging frameworks from simple starting materials. Impressive examples are the bisorbicillinoids, a family of fungal natural products thought to originate from the polyketide precursor sorbicillin. Utilizing the recombinant oxidoreductase SorbC from the sorbicillin biosynthetic gene cluster, a robust, fully stereoselective synthesis of bisorbicillinoid natural products and unnatural side-chain analogues was developed.