Total syntheses of spirocyclic PKS-NRPS-based fungal metabolites

Since the first isolation of pseurotin A in 1976, over twenty five spirocyclic PKS-NRPS-based (polyketide synthase-nonribosomal peptide synthetase-based) fungal natural products have been discovered to date. The common 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione core of this family of natural products has served as a platform for the development of novel chemistry and resulted in the development of numerous new reactivities and synthetic strategies. Herein, we delineate all reported syntheses of spirocyclic PKS-NRPS-based fungal metabolites including our own recent contributions on this subject. We showcase how a biosynthetic consideration could lead to concise synthetic routes to this family of natural products.