A unified “top-down” approach for the synthesis of diverse lead-like molecular scaffolds

Abstract

A “top-down” synthetic approach enabled the step-efficient synthesis of 21 diverse novel molecular scaffolds. The scaffolds were derived from four complex intermediates that had been prepared using cycloaddition chemistry. Scaffold-hopping of these intermediates was achieved through attachment of an additional ring, ring cleavage, ring expansion and/or ring fusion. It was shown that the resulting scaffolds could be decorated to yield diverse lead-like screening compounds.