title: Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization.
abstract: 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 generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure-activity relationship (SAR) studies were also undertaken.
authors.affiliation: Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo, Kita-ku, Hokkaido 060-0810, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oguri
authors.forename: Haruki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oikawa
authors.forename: Aki
authors.initials: A
authors.lastname: Ishiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Otoguro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura