Andrew Myers

Amory Houghton Professor of Chemistry and Chemical Biology

12 Oxford St.
Cambridge, MA 02138
Tel: 617-495-5679
Email: myers@chemistry.harvard.edu

Website:
http://www.chem.harvard.edu/groups/myers/index.html
Lab Size: Greater than 15

Summary
Professor Myers' research program involves the synthesis and study of complex molecules of importance in biology and human medicine. His group has developed laboratory synthetic routes to a broad array of complex natural products, including the ene-diyne antibiotics neocarzinostatin chromophore, dynemicin A, N1999A2, and kedarcidin chromophore, undertakings greatly complicated by the chemical instability of all members of the class. His laboratory developed the first practical synthetic route to the tetracycline antibiotics, allowing for the synthesis of more than three thousand fully synthetic analogs (compounds inaccessible by semi-synthesis: chemical modification of natural products) by a scalable process. A portfolio of clinical candidates for the treatment of infectious diseases, all fully synthetic tetracycline analogs, are currently in development at Tetraphase Pharmaceuticals, a company founded by Myers. In addition, the Myers' laboratory has developed short, practical and scalable synthetic routes to the saframycin, cytochalasin, stephacidin B-avrainvillamide, and trioxacarin classes of natural antiproliferative agents, in each case by the modular assembly of simple components of similar synthetic complexity.

Myers and his students have also developed numerous reagents and procedures of general utility in the construction of complex molecules. These include the development of methodology for the preparation of highly enantiomerically enriched ketones, aldehydes, alcohols, carboxylic acids, organofluorine compounds, α-amino acids, and molecules containing quaternary carbon centers using pseudoephenamine and pseudoephedrine as chiral auxiliaries, a method for the reductive deoxygenation of alcohols that does not involve metal hydride reagents, methods for the stereoselective synthesis of alkenes from sulfonyl hydrazones, a stereospecific synthesis of allenes from propargylic alcohols, a 1,3-reductive transposition of allylic alcohols, a silicon-directed aldol addition reaction, a method for the reductive coupling of aldehydes and allylic alcohols, the discovery of the powerful reductant lithium amidotrihydroborate, the use α-amino aldehydes in synthesis, methods for the synthesis and transformation of diazo compounds, a highly diversifiable method for the synthesis of isoquinolines, as well as others.

Publications

Synthesis of Cortistatins A, K, J, and L. Alec Flyer, Chong Si, and Andrew G. Myers. Nature Chemistry. 2010, 2, 886.

A Multiply Convergent Platform for the Synthesis of Trioxacarcins. Jakub Svenda, Nick Hill, and Andrew G. Myers.  PNAS. 2011, 17, 6709.

A Practical, Convergent Route to the Key Precursor to the Tetracycline Antibiotics.     David Kummer, Derun Li, Amelie Dion, and Andrew G. Myers. Chemical Science.     2011, 2 (9), 1710 – 1718.

Pseudoephenamine: A Practical Chiral Auxiliary for Asymmetric Synthesis.  Marvin R. Morales, Kevin T. Mellem, and Andrew G. Myers. Angewandte Chemie, International Edition. 2012, 51 (19), 4568.

Component-Based Syntheses of Trioxacarcin A, DC-45-A1, and Structural Analogs. Daniel J. Smaltz, Jakub Švenda, and Andrew G. Myers. Nature Chemistry, 2013, In Press.