Bergstrom Professor of Chemistry
Research Areas: Organic, Organometallic, Synthesis, Catalysis, Chemical Biology, Imaging, Drug Delivery, Molecular Therapeutics
Education: B.S., 1969, Wilkes College; Ph.D., 1973, Yale University
Awards: N.I.H. Postdoctoral Fellow, 1974, Columbia University; A. P. Sloan Fellow, 1979; Eli Lilly Grantee Award, 1979; Dreyfus Teacher Scholar, 1980; Ernest Guenther Award, 1988; ICI Pharmaceutical Group's Stuart Award for Excellence in Chemistry, 1988; Arthur C. Cope Scholar Award, 1990; Alexander von Humboldt Stiftung Award, 1991; ASSU Teaching Award, 1991; Hoagland Prize for Undergraduate Teaching, Stanford, 1991; Fellow, American Academy of Arts and Sciences, 1992; Bing Teaching Award, Stanford, 1992; National Institutes of Health MERIT Award, 2003; Pfizer Research Award for Synthetic Organic Chemistry, 1995; American Chemical Society Award for Creative work in Synthetic Organic Chemistry, 1998; Dean's Award for Distinguished Teaching, 2000; Fellow, American Association for the Advancement of Science, 2001; American Chemical Society H.C. Brown Award for Creative Research in Synthetic Methods, 2003; Member National Academy of Science, 2003; National Institutes of Health MERIT Award, 2006; The Hamilton Award (U. Nebraska), 2008; Wilbur Lucius Cross Medal (Yale Graduate Alumni), 2010; Tetrahedron Prize for Creativity in Organic Chemistry, 2012; Prelog Medal (ETH, Switzerland), 2013.
Principal Research Interests
Our research involves studies in chemistry, biology, medicine, and materials science. We are affiliated with the Medical School, Imaging Center, Chemical Biology Program and Molecular Therapeutics Program. A special emphasis is placed on training and research in synthesis, inventing new reactions, and the use of synthesis to address problems of significance in biology and medicine including eradication of HIV/AIDS, overcoming resistant cancer, and treating cognitive disorders like Alzheimer’s disease. Our studies include: 1) the design and development of new reactions, methods, reagents, and strategies that introduce novel ways of synthesizing molecules of biological or medicinal significance; 2) synthetic and mechanistic organometallic chemistry with an emphasis on new catalytic reactions; 3) mode of action studies on medicinally important leads; 4) drug delivery and novel mechanisms of transport into cells including the design and development of new transporters of drugs and probes; 6) molecular imaging; 7) new therapeutic strategies to address unsolved medical problems; and 8) computer modeling and molecular recognition.
SYNTHESIS: The key to achieving the “ideal synthesis” and greener chemistry is step economy which in turn relies critically on the discovery or invention of new reactions. New reactions are to synthesis what words are to language. Without expanding our lexicon we are limited in what we can do. Wender group members have discovered or invented over 25 new reactions including metal catalyzed 2-, 3-, and 4-, and component reactions such as 3+2, 4+4, 4+2, 5+2, 6+2, 6+1, 5+2+1, 4+2+2, 2+2+1, 5+1+2+1, 2+2+2+2 cycloadditions. New reactions are being used in the synthesis of new therapeutic leads, ligands for catalysis and materials.
TRANSFORMATIVE THERAPIES: Another area of emphasis is the development of new strategies to treat disease. Current AIDS therapies stop disease progression by targeting the active virus. This is important but requires chronic treatment with associated cost, compliance and resistance problems. We seek to target the latent virus, a strategy which if successful could eradicate this disease. These studies involve design, synthesis, mechanistic biology, and preclinical research.
We are also investigating other medicinal leads selected for unique activity and special clinical promise like bryostatin, currently in clinical trials for the treatment of cancer. We have designed agents that are better than bryostatin in various assays and we can supply these agents through practical syntheses. Remarkably some of these agents facilitate learning in animal models of cognitive dysfunction. These are promising preclinical candidates for cancer and for Alzheimer’s disease. Related opportunities at the interface of synthesis, biology and medicine include studies on daphnanes, gnidimacrin and apoptolidin, formidable synthetic challenges with unique clinical promise.
A grand challenge in science is developing strategies for breaching biological barriers. In our studies, we use designed cell penetrating molecular transporters that enable passage of a wide range of molecules into cells, including small molecules, peptides, proteins, nucleic acids, and nanoparticles. This research opens new opportunities in chemotherapy, imaging, diagnostics, and stem cell research and establishes a new tool of exceptional breadth for studying biochemical pathways and for real time imaging. It is being used in preclinical studies on overcoming resistant cancer.