This project in the Organic and Macromolecular Chemistry Program is a continuation of studies on the design and development of fundamentally new reactions, reagents, and strategies for organic synthesis, with an emphasis on how three dimensional molecular features influence the formation of large rings. The synthesis of a variety of diastereomers of erythronolide A seco acid will be investigated based on the recently developed route to a protected form of the "natural" seco acid. The synthetic seco acid diastereomers will be used to study the relationship between seco acid configuration, conformation and macrolactone efficiency. Relevant to macrolactone biosynthesis, a new preparation of the putative biosynthetic precursor of all erythromycins, 6-deoxyerythronolide B, will be prepared. This will entail an investigation into stereoselectivities of acyclic beta-hydroxy radical reactions, an area of acyclic stereochemical control that has not been investigated. Finally, the preparation of an artificial macrolactonization enzyme will be initiated.
