 In drug discovery programs, Ugi multicomponent reactions have been valuable in generating large numbers of diverse compounds for use in chemical libraries for high throughput screening.  In our high-throughput screening of small molecule libraries for new anti-fibrotic targets, two promising lead structures were discovered, acyclic alpha,beta diamino amide derivative 1 , and cyclization-derived imidazoline 2 . These structures can be accessed traditionally by the Ugi multicomponent reaction, which provides stereoisomeric mixtures of products as a statistical mixture of all 4 stereoisomers. In our hit-to-lead programs, we wished to prepare enantiomerically pure analogs for biological testing.  Here, we describe a new synthesis that provides the stereoisomers selectively in enantiopure form. Our syntheses diverge late-stage from a common precursor 3 , whichisprepared in 7 steps respectively from commercially available compounds. Early in the synthesis, the stereocenters are set in a catalytic enantioselective Mannich reaction and retained throughout the rest of the synthesis. The enantioselective synthesis of these small molecules allows for their evaluation as anti-fibrotic treatments.

Enantioselective synthesis of imidazolines and a,�-diamino amides derived from Ugi multicomponent high throughput screening libraries

248th National Meeting (2014)

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