A significant part of our work has been influenced by explorations of the synthetic, mechanistic, structural, and biological consequences of ring strain. Bond angle and bond length distortions, torsional interactions, and transannular and nonbonding steric clashes notably alter the chemical and physical properties of organic molecules. Early on, we explored the conformational effects of five-membered heterocycles embedded in the macrocyclic ring system of Lissoclinum peptides. We have also taken advantage of the reactivity of a fused tricyclic substructure in furanosteroids toward aza-Michael additions, leading ultimately to a Phase II clinical PI-3K inhibitor. Furthermore, several of our natural product target molecules have inspired us to develop new synthetic strategies and tactics in order to overcome the substantial ring strain present in their polycyclic frameworks. Finally, the exquisite ring strain in bicyclo[1.1.0]butanes and methylenecyclopropanes has been a rich source of a serendipity-driven discovery of novel reaction pathways and unique heterocyclic scaffolds. This presentation will focus on diverse aspects of strain-release in the development of new synthetic methods in our laboratory.

<b>Award Address </b>(ACS Award for Creative Work in Synthetic Organic Chemistry sponsored by MilliporeSigma). Strain-release as a driving force in the synthesis of novel heterocyclic scaffolds

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Award Address (ACS Award for Creative Work in Synthetic Organic Chemistry sponsored by MilliporeSigma). Strain-release as a driving force in the synthesis of novel heterocyclic scaffolds