biostudies-literatureUnknown8Oguri HBy emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the geBeilstein journal of organic chemistry930-40https://www.ebi.ac.uk/biostudies/studies/S-EPMC3388883biostudies-literatureParallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization.PMC3388883Oikawa HIshiyama AOtoguro KMizoguchi HOguri HIwatsuki MOmura SfalseParallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization.By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the ge2012-01-01T00:00:00Z20122025-04-05T13:20:27.064Z2019-03-27T00:55:11ZS-EPMC33888832301584310.3762/bjoc.8.105