%0 Journal Article
%T Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization
%A Hiroki Oguri
%A Haruki Mizoguchi
%A Hideaki Oikawa
%A Aki Ishiyama
%J Beilstein Journal of Organic Chemistry
%D 2012
%I 
%R 10.3762/bjoc.8.105
%X 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¨Cactivity relationship (SAR) studies were also undertaken.
%K chemical diversity
%K divergent cyclization
%K indole alkaloids
%K modular assembly
%K rhodium-catalyzed cyclization¨Ccycloaddition
%K skeletal and stereochemical diversity
%U http://dx.doi.org/10.3762/bjoc.8.105