Jimmy Wu

Associate Professor of Chemistry

Research in the Wu group focuses on the development of new reactions for  synthesizing compounds that have potential therapeutic value.  These include (4+3) and (3+2) cycloadditions with indole, redox chain reactions, etc.  In particular, we have identified molecules that can up-regulate the secretion of GLP-1 (glucagon-like peptide-1), inhibit the growth of MRSA, and induce apoptosis in leukemia cells.  For each of these projects, we have teamed up with biological collaborators to study mechanisms of action and identify more potent analogues.

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Our group has also recently completed the first total syntheses of several members of the hydroxylated dimeric nuphar alkaloids.  These compounds, found in the yellow water lily (i.e. Nuphar japonicum, Nuphar lutea, and Nuphar pumilum), are able to induce apoptosis in model leukemia cell lines faster than any small molecule.  We have also reported on the synthesis of the 1st apoptotically-active monomeric analogues.  Insufficient apoptosis is strongly linked to cancer and autoimmune disorders.  There are also numerous diseases associated with excessive cell death such as AIDS, Alzheimer’s, Huntington’s, Parkinson’s disease, and amyotrophic lateral sclerosis (i.e. ALS / Lou Gehrig’s disease).  A better understanding of the biological basis of how the nuphar alkaloids can so rapidly induce cell death, may lead to novel points of intervention for the design of prospective therapeutics and other diseases attributed to abnormal apoptosis.

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Department:
Chemistry
Education:
A.B. Princeton University 1994-1998
Ph.D. Harvard University 2001-2005
NIH Postdoctoral Fellow Stanford University 2005-2007
Associate Chemist Merck Process Research 1999-2001

Selected Publications

“A Quinolinol-Based Small Molecule with Anti-MRSA Activity that Targets Bacterial Membrane and Promotes Fermentative Metabolism” Nair, D. R.; Chen, J.; Monteiro, J. M.; Josten, M.; Pinho, M.; Sahl, H.-G.; Wu, J.; Cheung, A. J. Antibiot. (Tokyo), 2017 July 12.

"Transition Metal-Free C3 Arylation of Indoles with Aryl Halides" Chen, J.; Wu, J. Angew. Chem. Int. Ed. 201756, 3951-3955.

“Stereoselective Synthesis and Biological Evaluation of C1-Epimeric and Desmethyl Monomeric Nuphar Analogues” Li, H.; Cooke, T. J.; Korotkov, A.; Chapman, C. W.; Eastman, A.; Wu, J. J. Org. Chem. 201782, 2648-2655.

“Synthetic Small Molecule GLP-1 Secretagogues Prepared by Means of a Three-Component Indole Annulation Strategy” Chepurny, O. G.; Leech, C. A.; Tomanik, M.; DiPoto, M. C.; Li, H.; Han, X.; Meng, Q.; Cooney, R. N.; Wu, J.; Holz, G. G. Sci. Rep. 2016, 28934.

“Enantioselective Formal Syntheses of 11 Nuphar Alkaloids and Discovery of Potent Apoptotic Monomeric Analogues” Li, H.; Korotkov, A.; Chapman, C. W.; Eastman, A.; Wu, J. Angew. Chem. Int. Ed. 2016, 55, 3509−3513.

“Dearomative Indole (3+2) Reactions with Azaoxyallyl Cations − New Method for the Synthesis of Pyrroloindolines” DiPoto, M. C.; Hughes, R. P.; Wu, J. J. Am. Chem. Soc. 2015, 137, 14861-14864.

“Vinylogous Mukaiyama−Michael Reactions of Dihydropyridinones” Li, H.; Wu, J. Org. Lett. 2015, 17, 54245427.

“Total Syntheses and Biological Evaluation of Both Enantiomers of Several Hydroxylated Dimeric Nuphar Alkaloids” Korotkov, A.; Li, H.; Chapman, C. W.; Xue, H.; MacMillan, J. B.; Eastman, A.; Wu, J. Angew. Chem. Int. Ed. 2015, 54, 10604-10607.

"Regioselective Formal Hydroamination of Styrenes with 1-Phenyl-1H-tetrazole-5-thiol" Savolainen, M. A.; Han, X.; Wu, J. Org. Lett. 201416, 4349−4351.

“Dearomative Indole (3+2) Cycloaddition Reactions” Li, H.; Hughes, R. P.; Wu, J. J. Am. Chem. Soc. 2014136, 62886296

"Markovnikov-Selective Hydrothiolation of Styrenes: Application to the Synthesis of Stereodefined Trisubstituted Olefins" Savolainen, M. A.; Wu, J. Org. Lett. 201315, 38023804.

"Redox Chain Reaction - Indole and Pyrrole Alkylation with Unactivated Secondary Alcohols" Han, X.; Wu, J. Angew. Chem. Int. Ed. 2013, 52, 4637−4640.

"Ga(III)-Catalyzed Three-Component (4+3) Cycloaddition Reactions" Han, X.; Li, H.; Hughes, R. P.; Wu, J. Angew. Chem. Int. Ed. 2012, 51, 10390−10393.

"Palladium-Catalyzed Allylic Fluorination of Cinnamyl Phosphorothioate Esters" Lauer, A. M.; Wu, J. Org. Lett. 2012, 14, 5138−5141.

"Phosphorothioic Acids as Surrogates for H2S - Synthesis of Chiral Tetrahydrothiophenes" Robertson, F. J.; Wu, J. J. Am. Chem. Soc. 2012, 134, 2775−2780.

"Cu(I)-Catalyzed, alpha-Selective, Allylic Alkylation Reactions between Phosphorothioate Esters and Organomagnesium Reagents" Lauer, A. M.; Mahmud, F.; Wu, J. J. Am. Chem. Soc. 2011, 133, 9119−9112. (This report was highlighted in Synfacts 2011, 9, 1009.)

"Direct Annulation and Alkylation of Indoles with 2-Aminobenzyl Alcohols Catalyzed by TFA” Robertson, F. J.; Kenimer, B. D.; Wu, J. Tetrahedron 2011, 67, 4327−4332. (Invited Contribution - Symposium in Print: Tetrahedron Young Investigators Award for Prof. Dean Toste)

"Ga(OTf)3-Catalyzed Direct Substitution of Alcohols with Sulfur Nucleophiles” Han, X.; Wu, J. Org. Lett. 2010, 12, 5780−5782.

"Convenient Synthesis of Allylic Thioethers from Phosphorothioate Esters and Alcohols” Robertson, F. J.; Wu, J. Org. Lett. 2010, 12, 2668−2671.

"Mild Two-Step Process for the Transition-Metal-Free Synthesis of Carbon−Carbon Bonds from Allylic Alcohols/Ethers and Grignard Reagents” Han, X.; Zhang, Y.; Wu, J. J. Am. Chem. Soc. 2010, 132, 4104−4106. (This report was highlighted in Synfacts 2010, 6, 700.)

"(3+2)-Cycloaddition Reactions of Oxyallyl Cations” Li, H.; Wu, J. Synthesis 2015, 47, 22−33.

"Review of Recent Advances in Nucleophilic C-F Bond-forming Reactions" Wu, J. Tetrahedron Lett. 201455, 4289–4294

"Diethylphosphorothioic Acid" Wu, J. Encyclopedia of Reagents for Organic Synthesis2014, DOI: 10.1002/047084289X.rn01667

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