Synthesis of complex and diverse compounds through ring distortion of abietic acid

Many compound screening collections are populated by members that possess a low degree of structural complexity. In an effort to generate compounds that are both complex and diverse, we have developed a strategy that uses natural products as a starting point for complex molecule synthesis. Herein we apply this complexity-to-diversity approach to abietic acid, an abundant natural product used commercially in paints, varnishes, and lacquers. From abietic acid we synthesize a collection of complex (as assessed by fraction of sp ³-hybridized carbons and number of stereogenic centers) and diverse (as assessed by Tanimoto analysis) small molecules. The 84 compounds constructed herein, and those created through similar efforts, should find utility in a variety of biological screens. Abietic acid was used as the starting point for the synthesis of 84 complex and diverse small molecules. Their complexity was assessed by the fraction of sp³-hybridized carbon atoms and the number of stereogenic centers, and their diversity was evaluated by Tanimoto analysis. The 84 compounds constructed herein, and those created through similar efforts, should find utility in a variety of biological screens.