The biosynthesis of natural products has been perfected over millions of years of evolution, resulting in the huge diversity of complex small organic molecules found in nature. The laboratory synthesis of these compounds continues to be at the forefront of organic synthesis, both in terms of driving forward the development of new reaction methodology, and in supplying biologically active substances for applications in medicinal chemistry and chemical biology. However, the total synthesis of natural products is often a laborious and inefficient process, requiring multiple chemical reactions and purification steps. In contrast, nature can assemble complex molecules with apparent ease from a relatively limited set of simple starting materials. My research program is founded on the belief that consideration of the biosynthetic origin of a complex natural product within the context of a total synthesis project can inspire new synthetic strategies, which will be of broad utility within the wider organic chemistry community. In particular, this approach seeks to understand and exploit the predisposed reactivity of natural products and biosynthetic intermediates. I will also give examples of how our synthetic results in the lab can provoke new biosynthetic hypotheses.
This presentation will focus mainly on our work on oxidative dearomatization reactions used in synthetic approaches to three families of Streptomyces metabolites: the merochlorins, the napyradiomycins and the naphterpins.