Organic & Biomolecular Chemistry 2011-04-07

Rapid synthesis and zebrafish evaluation of a phenanthridine-based small molecule library.

Lauren R Donaldson, Stephen Wallace, David Haigh, E Elizabeth Patton, Alison N Hulme

Index: Org. Biomol. Chem. 9(7) , 2233-9, (2011)

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Abstract

A Heck cyclisation approach is described for the rapid synthesis of a library of natural product-like small molecules, based on the phenanthridine core. The synthesis of a range of substituted benzylamine building blocks and their incorporation into the library is reported, together with a highly selective cis-dihydroxylation protocol that enables access to the target compounds in an efficient manner. Biological evaluation of the library using zebrafish phenotyping has led to the discovery of compound 20c, a novel inhibitor of early-stage zebrafish embryo development.