Laboratory of Joseph M. Ready
Department of Biochemistry
University of Texas Southwestern Medical Center
Dallas, Texas

The Ready group is engaged in the discovery and application of new chemical reactions, the total synthesis of complex molecules, and the discovery of biologically active small molecules.

The combined effect of three recent developments has created an enormous challenge and a fantastic opportunity for synthetic chemistry. First, the sequencing of the human genome has revealed a huge number of genes associated with human diseases, and the corresponding proteins represent potential drug targets. Second, the development of high-throughput screening methods has given scientists the ability to evaluate large collections of small molecules quickly and accurately. Finally, solid phase synthesis has been revolutionized by new techniques and equipment such that it is now possible to synthesize large libraries of defined molecules in usable quantities. Taken together, the situation facing pharmaceutical companies and academic researchers alike is that we have a platform to access many molecules, and means to test their effect on specific, relevant cellular targets. The great challenge now facing chemistry and, I believe, all of biomedical science, is the need for chemical reactions and protocols that are reliable, predictable and efficient. It is only through the development of such reactions that we can create the molecular diversity required to combat human diseases. Currently, only a limited number of reactions proceed selectively and quantitatively with a broad range of substrates. Thus the preparation of new compounds continues to be one of the slowest steps in drug discovery.

My research program focuses on three related areas of organic synthesis: development of synthetic methods, natural products synthesis, and drug discovery. We are interested in all areas of reaction development, including discovery, application and mechanistic study. In the context of reaction discovery, we are studying problems in organometallics, asymmetric catalysis and the chemistry of carbenes. Current research is directed toward the discovery of a catalytic system for enolate alkylation and the development of cycloadditions for the enantioselective synthesis of five-membered rings. Simultaneously, synthetic studies on natural products are guided by an interest in novel approaches to polycyclic skeletons. Target selection is influenced equally by issues of molecular complexity and biological activity. Finally, we are involved in collaborative efforts to identify small molecules with relevance to neurodegenerative diseases, cancer and virology. We anticipate that the combination of these efforts will greatly expand the power of organic chemistry and enable the rapid and efficient synthesis of valuable complex molecules.

Examples of research projects from the group are given below.

Publications

pdf Wang, Y.; Wang, C.; Butler, J. R.; Ready, J. M. “Dehydrogenative Coupling to Enable the Enantioselective Total Synthesis of (-)-Simaomicin a.” Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201304812.
pdf Naidoo, J.; Bemben, C. J.; Allwein, S. R.; Liang, J.; Pieper, A. A.; Ready, J. M. “Development of a Scalable Synthesis of P7C3-A20, a Potent Neuroprotective Agent.” Tetrahedron Lett. 2013, 54, 4429.
pdf Kilgore, J. A.; Du, X.; Melito, L.; Wei, S.; Wang, C.; Chin, H. G.; Posner, B.; Pradhan, S.; Ready, J. M.; Williams, N. S.* “Identification of DNMT1 Selective Antagonists Using a Novel Scintillation Proximity Assay.” J. Biol. Chem. 2013, 288, 19673.
pdf Antczak, M.; Ready, J.M. “Two-, Three-, and Four-Component Coupling to form Isoquinolones Based on Directed Metalation.” Chem. Sci. 2012, 3, 1450-1454.
pdf De Jesús-Cortés, H.; Xu, P.; Drawbridge, J.; Estill, S. J.; Huntington, P.; Tran, S.; Britt, J.; Tesla, R.; Morlock, L.; Naidoo, J.; Melito, L. M.; Williams, N. S.; Ready, J. M.; McKnight, S. L.; Pieper, A. A. “Neuroprotective Efficacy of Aminopropyl Carbazoles in a Mouse Model of Parkinson’s Disease.” Proc. Natl. Acad. Sci. USA, 2012, doi: 10.1073/pnas.1213956109.
pdf Tesla, R.; Wolf, H. P.; Xu, P.; Drawbridge, J.; Estill, S. J.; Huntington, P.; McDaniel, L.; Knobbe, W.; Morlock, L.; Naidoo, J.; Williams, N. S.; Ready, J. M.; McKnight, S. L.; Pieper, A. A. “Neuroprotective Efficacy of Aminopropyl Carbazoles in a Mouse Model of Amyotrophic Lateral Sclerosis.” Proc. Natl. Acad. Sci. USA, 2012, doi: 10.1073/pnas.1213960109.
pdf Wang, Y.; Ready, J.M. "Cyclocondensation of Amino-propargyl Silanes" Org. Lett. 2012, 14, 2308-2311.
pdf Cai, F.; Pu, X.; Qi, X.; Lynch, V.; Radha, A.; Ready, J.M. "Chiral Allene-Containing Phosphines in Asymmetric Catalysis" J. Am. Chem. Soc. 2011, 133, 18066-18069.
pdf Butler, J.R.; Wang, C.; Bian, J.; Ready, J.M. "Enantioselective Total Synthesis of (-)-Kibdelone C" J. Am. Chem. Soc. 2011, 133, 9956-9959.
pdf Lee, K.S.; Ready, J.M. “Oxidative Arylation of Homoallylic Alcohols” Angew. Chem. Int. Ed. 2011, 50, 2111-2114.
pdf MacMillan, K.S.; Naidoo, J.; Liang, J.; Melito, L.; Williams, N.S.; Morlock, L.; Huntington, P.J.; Estill, S.J.; Longgood, J.;. McKnight, S.L.; Pieper, A.A.; De Brabander, J.K, Ready, J.M. "Development of Proneurogenic, Neuroprotective Small Molecules" J. Am. Chem. Soc. 2011, 133, 1428-1437
pdf Antczak, M. I.; Cai, F.; Ready, J. M. "Asymmetric Synthesis of Tertiary Benzylic Alcohols" Org. Letters, 2011, 13, 184-187.
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Pieper, A.A.; Xie, S.; Capota, E.; Estill, S.J.; Zhong, J.; Long, J.M.; Becker, G.L.; Huntington.; Goldman, S.E.; Shen, C.H.; Capota, M.; Britt, J.K.; Kotti, T.; Brat, D. J.; Williams, N.S.; MacMillan, K.S.; Naidoo, J.; Melito, L.; Hsieh, J.; De Brabander, J.; Ready, J.M.; McKnight, S.L. “Discovery of a pro-neurogenic, neuroprotective chemical” Cell 2010, 142, 39-51.

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Pu, X.; Qi, X.; Ready, J. M. “Allenes in Asymmetric Catalysis: Asymmetric Ring Opening of meso-Epoxides Catalyzed by Allene-Containing Phosphine Oxides” J. Am. Chem. Soc. 2009, 131, 10364-10365.

pdf Espindola, A.P.D.M.; Crouch, R.; DeBergh, J.R.; Ready, J.M.; MacMillan, J.M. "Deconvolution of Complex NMR Spectra in Small Molecules by Multi-Frequency Homonuclear Decoupling (MDEC)" J. Am. Chem. Soc. 2009, 131, 15994-15995.
pdf Qi, X.; Ready, J. M. “Synthesis of Cyclopentenones from Cyclopropanes and Silyl Ynol Ethers” Angew. Chem. Int. Ed. 2008, 47, 7068-7070. 
pdf Pu, X; Ready, J. M. “Direct and Stereospecific Synthesis of Allenes via Reduction of Propargylic Alcohols with Cp2Zr(H)Cl” J. Am. Chem. Soc. 2008, 130, 10874-10875.
pdf DeBergh, J. R.; Spivey, K. M.; Ready, J. M. “Preparation of Substituted Enol Derivatives from Terminal Alkynes and Their Synthetic Utility” J. Am. Chem. Soc. 2008, 130, 7828-7829.
pdf Liu, X.; Ready, J. M. “Directed Hydrozirconation of Homopropargylic Alcohols” Tetrahedron, 2008, 64, 6955-6960.
pdf Zhang, D. H.; Ready, J. M. "Directed Hydrozirconation of Propargylic Alcohols" J. Am. Chem. Soc. 2007, 129, 10288-10289
pdf Germanas, J. P.; Wang, S.; Miner, A.; Hao, W.; Ready, J. M. "Discovery of Small-Molecule Inhibitors of Tyrosinase" Bioorg. Med. Chem. Lett. 2007, 6871-6875.
pdf Lynch, K. W.; Ready, J. M. "Sceince at the Interface of Chemistry and Biology at UT Southwestern" ACS Chem. Biol. 2007, 512-514.
pdf Qi, X.; Ready, J. M. "Copper-Promoted Cycloaddition of Diazocarbonyl Compounds with Copper Acetylides" Angew. Chem. Int. Ed. 2007, 46, 3242-3244.
pdf Zhang, D. H.; Ready, J. M. "Iron-Catalyzed Carbometalation of Propargylic and Homopropargylic Alcohols" J. Am. Chem. Soc. 2006, 128, 15050-15051.
pdf Bian, J.; Wingerden, M. V.; Ready, J. M. “Enantioselective Total Synthesis of (+)- and (-)-Nigellamine A2” J. Am. Chem. Soc. 2006, 128, 7428-7429.
pdf Reisman, S. E.; Ready, J. M.; Hasuoka, A.; Smith, C. J.; Wood, J. L. “Total Synthesis of Welwitindolinone A Isonitrile” J. Am. Chem. Soc. 2006, 128, 1448-1449.
pdf Zhang, D. H.; Ready, J. M. “Tandem Carbocupration/Oxygenation of Terminal Alkynes” Org. Lett. 2005, 7, 5681-5683.
pdf Malosh, C. F.; Ready. J. M. “Catalytic Cross-Coupling of Alkylzinc Halides with α-Chloroketones” J. Am. Chem. Soc. 2004, 126, 10240-10241.
pdf Ready, J. M.; Reisman, S. E.; Hirata, M.; Weiss, M. M.; Tamaki, K.; Ovaska, T.; Wood, J. L. “A Mild and Efficient Synthesis of Oxindoles: Application to the Synthesis of Welwitindolinone A Isonitrile.” Angew. Chem. Int. Ed., 2004, 43, 1270-1272.
pdf Ready, J. M.; Jacobsen, E. N. “A Practical Oligomeric [(salen)Co] Catalyst for Asymmetric Epoxide Ring-Opening Reactions.” Angew. Chem. Int. Ed., 2002, 41, 1374-1377.
pdf Ready, J. M.; Jacobsen, E. N.  “Highly Active Oligomeric (salen)Co Catalysts for Asymmetric Epoxide Ring Opening Reactions.”  J. Am. Chem. Soc. 2001, 123, 2687-2688.
pdf Ready, J. M.; Jacobsen, E. N. "Asymmetric Catalytic Synthesis of a-Aryloxy Alcohols:  Kinetic Resolution of Terminal Epoxides via Highly Enantioselective Ring Opening with Phenols" J. Am. Chem. Soc. 1999, 121, 6086-6087.

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Page maintained by Joseph Ready
Last updated Sept, 2013