Scott Miller

Searching for Selective Reactions on Complex Molecular Scaffolds

Complexity is a relative term that is often used to describe features of molecules that contain multiple functional groups or which exhibit difficult-to-control dynamics. As such, the discovery of catalysts that perform selective reactions on complex substrates presents a myriad of challenges. Certain natural products may be archetypical of complex scaffolds that present challenges for the development of selective reactions. More generally, natural products have provided perennial inspiration for the development of synthetic methods. In parallel, enzymes have provided an analogous platform for the study of catalysis and the conception of new catalysts. This lecture will recount an interplay of experiments stimulated by these two major classes of naturally occurring substances – natural products and enzymes – as we have endeavored to discover catalysts that mediate selective bond-forming reactions on complex molecules. Specifically, the discovery and use of peptides as catalysts for a variety of asymmetric bond formations will be presented. Likewise, applications of these catalysts to the selective modification of complex molecules, including biologically active natural products, will be described. A particular emphasis will be placed on reactions that present unusual stereochemical challenges. An analysis of catalyst types that may be brought to bear on complex molecular environments will also be included.