GSA Lecture Presentation by Dr. Andrew G. Myers, Harvard University

Graduate Student Association lecture presentation by Dr. Andrew G. Myers, Professor and Chair, Harvard University.

Title: "Evolution of a fully synthetic route to the tetracyclines and its implementation in the discovery of new antibiotics"

Abstract: The emergence of resistance in bacteria to virtually all known antibiotics, including the tetracyclines, and the diminishing number of new antibiotics in line for clinical approval presents a serious public-health problem.  With a few important exceptions (the quinolone and oxazolidinone antibiotics, to name two), the development of new antibiotics has largely been the province of semi-synthesis, or the chemical modification of complex fermentation products. For example, for more than five decades the development of new macrolide and tetracycline antibiotics has followed a slow human-directed evolutionary path using natural product starting materials.  This is largely a consequence of the fact that scalable laboratory synthetic routes in both series have been lacking.  In this lecture I will describe our efforts to develop a practical synthetic route to the tetracyclines, widely diversifiable at key positions, and the use of the route to identify new antibiotics that are active in strains of Gram-positive and Gram-negative bacteria with multiple resistance mechanisms to conventional tetracyclines.

Key References:

 A Convergent Enantioselective Route to Structurally Diverse 6-Deoxytetracycline Antibiotics.
Mark G. Charest, Christian D. Lerner, Jason D. Brubaker, Dionicio R. Siegel and Andrew G. Myers
Science 2005, 308, 395

- A Robust Platform for the Synthesis of New Tetracycline Antibiotics.
Cuixiang Sun, Qui Wang, Jason D. Brubaker, Peter M. Wright, Christian D. Lerner, Kevin Noson, Mark Charest, Dionicio R. Siegel, Yi-Ming Wang and Andrew G. Myers
J. Am. Chem. Soc. 2008, 130, 17913