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.

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 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.

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 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 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 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.

1. "Synthesis at the Molecular Frontier,"Nature, 460, 197-201 (2009).

2. "Function Oriented Synthesis, Step Economy, and Drug Design," Accts. Chem. Res, 40-49 (2008).

3. "Practical Synthesis of Prostratin, DPP, and Their Analogs, Adjuvant Leads Against Latent HIV," Science, 649-652 (2008).

4. "Efficient Synthetic Access to a New Family of Highly Potent Bryostatin Analogues via a Prins-Driven Macrocyclization Strategy," J. Am. Chem. Soc., 6658-6659 (2008).

5. "Oligocarbonate Molecular Transporters: Oligomerization Based Syntheses & Cell Penetrating Studies," J. Am. Chem. Soc., ASAP (2009).

6. "Prolonging Microtubule Dysruption Enhances the Immunogenicity of Chronic Lymphocytic Leukemia Cells," Clinical & Experimental Immunology, 158, 186-198 (2009).

7. "The Synthesis of Highly-Substituted Cyclooctatetraene Scaffolds by Metal-Catalyzed [2 2 2 2] Cycloadditions: Studies on Regioselectivity, Dynamic Properties and Metal Chelation," Angewandte Chemie Int. Ed., 7823-7826 (2009).

8. "Cyclocarboamination of Alkynes with Aziridines: Ķ a Catalyzed Formal [3 2] Cycloaddition," J. Am. Chem. Soc., 7528-7529 (2009).

9. "A Cellular Model of Alzheimer's Disease Therapeutic Efficacy: PKC Activation Reverses A-beta induced biomarker Abnormality on Cultured Fibroblasts," Neurobiology of Disease, 332-339 (2009).

10. "A Pro-apoptotic Signaling Pathway involving RasGRP, Erk and Bim in B Cells," Experimental Hematology, 122-134 (2009).

11. "Overcoming Multidrug Resistance of Small Molecule Therapeutics through Conjugation with Releasable Octaarginine Transporters," Proc. Natl. Acad. Sci. USA, 12128-12133 (2008).

12. "Origins of Differences in Reactivities of Alkenes, Alkynes, and Allenes in [Rh(CO)2Cl]2-Catalyzed (5 2) Cycloaddition Reactions with Vinylcyclopropanes," J. Am. Chem. Soc., 2378-2379 (2008).