Dale L. Boger
Dr. Dale L. Boger is an internationally recognized leader in organic synthesis, natural products total synthesis, synthetic methodology development and medicinal chemistry. His work encompasses the synthesis of extraordinarily complex molecules followed by systematic structure–function studies that reveal the molecular basis of their biological activity. His contributions to understanding and improving the glycopeptide antibiotics, particularly vancomycin, have produced durable antibiotics capable of overcoming resistance that has developed to one of medicine's most important drugs.
Boger was born on August 22, 1953, in Hutchinson, Kansas. He received his B.S. in chemistry from the University of Kansas in 1975, graduating with highest distinction and honors in chemistry. He earned his Ph.D. from Harvard University in 1980 under the direction of E. J. Corey, supported by an NSF fellowship. He returned to the University of Kansas as a faculty member in the Department of Medicinal Chemistry from 1979 to 1985, then moved to the Department of Chemistry at Purdue University where he was associate professor and professor of chemistry from 1985 to 1991. He joined the faculty in the newly created Department of Chemistry at The Scripps Research Institute in 1991 as the Richard and Alice Cramer Professor of Chemistry. He served as Chairman of the Department of Chemistry from 2012 to 2018 and is a member of the Skaggs Institute for Chemical Biology.
Boger's synthetic methodology contributions include the development and application of hetero Diels–Alder reactions, thermal reactions of cyclopropenone ketals, intermolecular and intramolecular acyl radical–alkene addition reactions, medium and large ring cyclization procedures, iron(III)-mediated hydrogen atom transfer free radical functionalization of unactivated alkenes, and solution-phase combinatorial chemistry. In each case the methodology was developed in the context of a projected key step in the total synthesis of a natural or designed product.
His natural product syntheses are selected based on important biological properties. Major achievements include total syntheses of vinblastine, vincristine and related Vinca alkaloids used in cancer chemotherapy; CC-1065 and the duocarmycins, antitumor antibiotics that exhibit sequence-selective DNA alkylation; bleomycin A2, a clinically employed antitumor agent; and the glycopeptide antibiotics vancomycin, teicoplanin, ristocetin and chloropeptins. His studies of CC-1065 and the duocarmycins established fundamental relationships between structure, reactivity and biological activity for these potent DNA-alkylating agents, defining the molecular basis of their sequence-selective recognition of DNA.
Boger's work on vancomycin exemplifies his approach of combining total synthesis with systematic structure–function investigation. First discovered in 1956, vancomycin remained effective against resistant bacterial strains for decades because of its unusual mechanism of action: binding to cell wall precursors and preventing the cross-linking that provides structural integrity. Researchers had not determined the complete chemical structure until 1982. In 1999 Boger became one of the first to complete a total synthesis of vancomycin, a chemical feat of extraordinary complexity. When vancomycin-resistant bacteria finally emerged through gene transfer from the organisms that naturally produce the antibiotic, Boger's team found that replacing a single oxygen atom in vancomycin restored binding to the altered target. His laboratory went on to develop vancomycin analogs that act through multiple mechanisms of action, providing durable antibiotics effective against both vancomycin-sensitive and vancomycin-resistant organisms including multidrug-resistant and vancomycin-resistant Staphylococcus aureus. These modified glycopeptides, termed maxamycins, represent some of the most promising candidates for overcoming antibiotic resistance.
Boger has also made seminal contributions to understanding fatty acid amide signaling and the discovery of new therapeutic targets. His laboratory developed the first class of selective, exceptionally potent, reversible and competitive inhibitors of fatty acid amide hydrolase, the enzyme responsible for degrading oleamide, an endogenous sleep-inducing lipid, and anandamide, an endogenous ligand for cannabinoid receptors. These inhibitors display efficacious activity in models of chronic and neuropathic pain and inflammation, representing a potential new approach to pain treatment that works through the endocannabinoid system.
Boger served as Founding Editor and Editor-in-Chief of Bioorganic and Medicinal Chemistry Letters from 1990 to 2015 and was an Executive Editorial Board Member of Tetrahedron Publications during the same period.
His achievements have been recognized with numerous awards including the Searle Scholar Award in 1981, an NIH Research Career Development Award from 1983 to 1988, an Alfred P. Sloan Fellowship from 1985 to 1989, the ACS Arthur C. Cope Scholar Award in 1988, the ISHC Katritzky Award in 1997, the ACS Award for Creativity in Organic Synthesis in 1999, the Paul Janssen Prize for Creativity in Organic Synthesis in 2002, the Royal Society of Chemistry Adrien Albert Medal in 2003, the ACS Guenther Award in Chemistry of Natural Products in 2007, the ACS Ralph F. Hirschmann Award in Peptide Chemistry in 2013, and the American Association for Cancer Research Award in Chemistry in 2014. He was elected to the American Academy of Arts and Sciences in 2006 and to the National Academy of Sciences in 2014. He is a Fellow of the American Association for the Advancement of Science, the Royal Society of Chemistry and the American Chemical Society. In 2016 he was elected to the National Academy of Inventors. Additional honors include the RSC Robert Robinson Award in 2017, an NIH MERIT Award in 2018, the ISHC E. C. Taylor Award and the Kitasato Microbial Chemistry Medal in 2019, and the Tetrahedron Prize in 2020. In 2023 he received the Distinguished Alumni Award from the University of Kansas.
