Jean-Luc MONTCHAMP

Professor (Organic and Bioorganic Chemistry)

J.MONTCHAMP@TCU.EDU

Phone: (817) 257 6201 / Fax: (817) 257 5851

Ph.D., Purdue University
Postdoctoral: Michigan State University, The Scripps Research Institute, Purdue University

FUNDING: we gratefully acknowledge the following for the current financial support of our research:

The Robert A. Welch Foundation

The National Science Foundation

CONGRATULATIONS TO PROFESSOR Ei-ichi NEGISHI, 2010 WINNER OF THE CHEMISTRY NOBEL PRIZE!

Our group's research interests are in the areas of organophosphorus chemistry, and bioorganic/medicinal chemistry.
Current methodology aims at alleviating the use of phosphorus trichloride in the synthesis of organophosphorus compounds. While the majority of phosphorus compounds are prepared from PCl3, the chlorine atoms are generally not incorporated in the final products. Thus methodology based on hypophosphorous compounds provides an environmentally friendly ("green") approach to organophosphorus compounds containing a P-C bond. reactions we have developed, such as hydrophosphinylation, cross-coupling (including allylic and benzylic alcohols) and the catalytic oxidation of H-phosphinates, are providing new and efficient approaches to a variety of compounds.

The core of our program in chemical biology focuses on the mechanism-based design, synthesis and evaluation of biologically active molecules such as enzyme inhibitors, and the development of novel antisense oligonucleotides with emphasis on the application of automated synthesis and combinatorial techniques whenever possible. Unnatural compounds are synthesized to probe various biological processes. Applications of this research range from the elucidation of enzyme mechanisms to the preparation of molecules with potential medicinal use (anticancer, antiparasite, immuno suppressant, antisense, GABA analogues). One such medicinally oriented goal is the preparation and evaluation of new hydrolytically stable antisense oligonucleotides for sequence specific complexation to RNA and DNA targets. Finally, current investigations aiming at the modulation of GABA receptors with phosphinic analogues are relevant to the treatment of various central nervous system (CNS) disorders. A collaborative project with Professor Coffer has also been initiated to prepare the recognition component of biocompatible calcified nanoporous silicon sensor arrays. Another collaborative project with Professor Anne F. Richards deals with the synthesis of phosphorus-containing building blocks for the preparation of metal-organic frameworks (MOFs).

Our second research interest concerns organophosphorus chemistry and is driven by two main objectives: firstly, the development of P-chiral ligands to be ultimately used in catalytic asymmetric transformations, including transition metal-catalyzed reactions, and secondly, the building of a methodology based on phosphorus compounds for organic synthesis as well as for the preparation of compounds possessing potential biological activity.
Our program toward the development of new methodology for the synthesis of phosphinic acids has led to several novel reactions, including the palladium-catalyzed cross-coupling of hypophosphite derivatives with aryl, benzylic, and alkenyl electrophiles, and the room temperature radical addition of hypophosphites to olefins. These reactions are applied to the synthesis of biologically active compounds, and to the preparation of P-chiral building blocks.
Combining the above research directions in the same program provides valuable advantages. Because phosphorus is ubiquitous in nature, a variety of molecules can be designed to achieve some specific biological effect. To achieve the efficient synthesis of such compounds, new synthetic routes will be required, which could borrow from independently developed methodologies. In general, a combination of organic synthesis, methodology, and chemical biology, will be used to pursue our objectives.

Methodological Summary

PUBLICATIONS

“Mixed 1,1-Bis-Phosphorus Compounds: Synthesis, Alkylation, and Horner-Wadsworth-Emmons Olefination Reactions” Ortial, S.; Thompson, D. A.; Montchamp, J.-L. J. Org. Chem 2010, x, submitted

“Strategies for the asymmetric synthesis of H-phosphinate esters” Bravo-Altamirano, K.; Coudray, L.; Montchamp, J.-L. Org. Biomol. Chem 2010, x, in press

“Regiocontrol in the Palladium-Catalyzed Hydrophosphinylation of Terminal Alkynes” Belabassi, Y.; Bravo-Altamirano, K.; Montchamp, J.-L. J. Organomet. Chem 2010, x, in press

“Synthesis and Reactivity Studies of a,a-Difluoromethylphosphinates” Abrunhosa-Thomas, I.; Coudray, L.; Montchamp, J.-L. Tetrahedron 2010, 66, 4434

“Facile P,N-heterocycles synthesis via tandem aminomethylation-cyclization of H-phosphinates building blocks” Queffelec, C.; Montchamp, J.-L. Org. Biomol. Chem 2010, 8, 267

“Synthesis and In Vitro Evaluation of Aspartate Transcarbamoylase Inhibitors” Coudray, L.; Pennebaker, A. F.; Montchamp, J.-L. Bioorg. Med. Chem. 2009, 17, 7680

“Temporary Protection of H-Phosphinic Acids as a Synthetic Strategy” Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem 2009, 4646

“Reactions of a-Boranophosphorus Compounds with Electrophiles: Alkylation, Acylation, and other Reactions” Antczak, M. I.; Montchamp, J.-L. J. Org. Chem 2009, 74, 3758

“Prodrug Surface Modification of Silicon Nanowires: Impact on Calcification and Stromal Cell Proliferation” Jiang, K.; Fan, D.; Belabassi, Y.; Akkaraju, G.; Montchamp, J.-L.; Coffer, J. L. ACS Appl. Mat. Interfaces 2009, 1, 266

“Submicromolar Phosphinic Inhibitors of E. coli Aspartate Transcarbamoylase” Coudray, L.; Kantrowitz, E. R.; Montchamp, J.-L. Bioorg. Med. Chem. Lett. 2009, 19, 900

“A Facile Synthesis and Crystallographic Analysis of Seven Trityl Phosphorus Compounds and Two Nickel(II) Phosphine Side-Products” Gushwa, A. F.; Belabassi, Y.; Montchamp, J.-L., Richards, A. F. J. Chem. Cryst. 2009, 39, 337

“Synthesis of P,N-Heterocycles from w-Amino-H-Phosphinates: Conformationally Restricted a-Aminoacid Analogs” Queffelec, C.; Ribière, P.; Montchamp, J.-L. J. Org. Chem. 2008, 73, 8987

“Synthesis of 1,1-Bis-Phosphorus Compounds from Organoboranes” Antczak, M. I.; Montchamp, J.-L. Tetrahedron Lett. 2008, 49, 5909

“Revisiting the Hirao Cross-Coupling: Improved Synthesis of Aryl & Heteroaryl Phosphonates” Belabassi, Y.; Alzghari, S.; Montchamp, J.-L. J. Organomet. Chem. 2008, 693, 3171

“5-Pyrimidyl Phosphonic Acid as a Building Block for the Synthesis of Coordination Polymers” Samanamu, C. R.; Zamora, E. N.; Lesikar, L. A.; Montchamp, J.-L.; Richards, A. F. Cryst. Eng. Comm. 2008, 10, 1372

“Borane Complexes of the H3PO2 P(III) Tautomer: Useful Phosphinate Equivalents” Belabassi, Y.; Antczak, M. I.; Tellez, J.; Montchamp, J.-L. Tetrahedron 2008, 64, 9181

“Green, Palladium-Catalyzed Synthesis of Benzylic H-Phosphinates from Hypophosphorous Acid and Benzylic Alcohols” Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2008, 4101

“Recent Developments in the Addition of Phosphinylidene-Containing Compounds to Unactivated Unsaturated Hydrocarbons: Phosphorus-Carbon Bond-Formation via Hydrophosphinylation and Related Processes” Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2008, 3601

“Structural Analogues of Bioactive Phosphonic Acids: First Crystal Structure Characterization of Phosphonothioic and Boranophosphonic Acids” Belabassi, Y.; Gushwa, A. F.; Richards, A. F.; Montchamp, J.-L. Phosphorus, Sulfur and Silicon and the Related Elements 2008, 183, 2214

“Synthesis of Homo and Hetero Metal-Phosphonate Frameworks from Bi-Functional Aminomethylphosphonic acid” Samanamu, C. R.; Zamora, E. N.; Montchamp, J.-L.; Richards, A. F. J. Solid State Chem. 2008, 181, 1462

“Allylic Phosphinates via Palladium-Catalyzed Allylation of H-Phosphinic Acids with Allylic Alcohols”Coudray, L.; Bravo-Altamirano, K.; Montchamp, J.-L.. Org. Lett. 2008, 10, 1123

“Mild Synthesis of Organophosphorus Compounds: Reaction of Phosphorus-Containing Carbenoids with Organoboranes” Antczak, M. I.; Montchamp, J.-L. Org. Lett. 2008, 10, 977.

“Palladium-Catalyzed Reactions of Hypophosphorous Compounds with Allenes, Dienes and Allylic Electrophiles: Methodology for the Synthesis of Allylic-H-Phosphinates” Bravo-Altamirano, K.; Abrunhosa-Thomas, I.; Montchamp, J.-L. J. Org. Chem. 2008, 73, 2292

“ Convenient Synthesis of Aluminum and Gallium Phosphonate Cages” Samanamu, C. R.; Olmstead, M. M.; Montchamp, J.-L.; Richards, A. F. Inorg. Chem. 2008, 47, 3879

“Palladium-Catalyzed Dehydrative Allylation of Hypophosphorous Acid with Allylic Alcohols. Preparation of Cinnamyl-H-Phosphinic Acid” Bravo-Altamirano, K.; Montchamp, J.-L. Org. Synth. 2008, 85, 96

“A Mild Synthetic Route to Zinc, Cadmium, and Silver Polymers with 2-Pyridyl Phosphonic Acid: Synthesis and Analysis ” Fry, J. A.; Samanamu, C. R.; Montchamp, J.-L.; Richards, A. F. Eur. J. Inorg. Chem. 2008, 463

“New Access to H-Phosphonates via Metal-Catalyzed Phosphorus-Oxygen Bond Formation” Coudray, L.; Abrunhosa-Thomas, I.; Montchamp, J.-L. Tetrahedron Lett. 2007, 48, 6505

“A Novel Approach to Phosphonic Acids from Hypophosphorous acid” Bravo-Altamirano, K., Montchamp, J.-L. Tetrahedron Lett. 2007, 48, 5755.

“Alkylation of H-Phosphinate Esters under Basic Conditions” Abrunhosa-Thomas, I.; Sellers, C. E., Montchamp, J.-L. J. Org. Chem. 2007, 72, 2851.

“AIBN-initiated Radical Reactions of Ethyl Phosphinate” Antczak, M. I.; Montchamp, J.-L. Synthesis 2006, 3080.

“Palladium-Catalyzed Dehydrative Allylation of Hypophosphorous Acid with Allylic Alcohols” Bravo-Altamirano, K.; Montchamp, J.-L. Org. Lett. 2006, 8, 4169.

“Advances in the Synthesis of H-Phosphinic Acids and Esters” Montchamp, J.-L. Specialty Chemicals Magazine 2006, 26, 44.

"Direct Monoalkylation of Alkyl Phosphinates to Access H-Phosphinic Acid Esters”
Abrunhosa-Thomas, I.; Ribière, P.; Adcock, A. C.; Montchamp, J.-L. Synthesis 2006, 325.

“Radical Reaction of Sodium Hypophosphite with Terminal Alkynes: Synthesis of 1,1-bis-H-Phosphinates”
Gouault-Bironneau, S.; Deprèle, S.; Sutor, A.; Montchamp, J.-L. Org. Lett. 2005, 7, 5909.

“Palladium-Catalyzed Phosphorus-Carbon Bond Formation: Cross-Coupling Reactions of Alkyl Phosphinates with Aryl, Heteroaryl, Alkenyl, Benzylic, and Allylic Halides and Triflates”
Bravo-Altamirano, K.; Huang, Z.; Montchamp, J.-L. Tetrahedron 2005,61, 6315.

"NiCl2-Catalyzed Hydrophosphinylation", Ribiere, P.; Bravo-Altamirano, K.; Antczak, M. I.; Hawkins, J. D.; Montchamp, J.-L. J. Org. Chem. 2005, 70, 4064.

"Recent Advances in Phosphorus-Carbon Bond Formation: Synthesis of H-Phosphinic Acid Derivatives from Hypophosphorous Compounds", Montchamp, J.-L. J. Organomet. Chem., 2005, 690, 2388

"Environmentally Benign Synthesis of H-Phosphinic Acids Using a Water-Tolerant, Recyclable Polymer-Supported Catalyst", Deprèle, S.; Montchamp, J.-L. Org. Lett. 2004, 6, 3805.

"Direct Synthesis of H-Aryl and H-Heteroarylphosphinic Esters via Palladium-Catalyzed Cross-Coupling of Alkylphosphinates", Huang, Z.; Bravo-Altamirano, K.; Montchamp, J.-L. Comptes Rendus Chimie 2004, 7/8-9, 763.

"Routes to Calcified Porous Silicon: Implications for Drug Delivery and Biosensing", Coffer, J. L.; Montchamp, J.-L.; Aimone, J. B.; Weis, R. P. Physica Status Solidi (a) 2003, 197, 336.

"Calcified Nanostructured Silicon Wafer Surfaces for Biosensing: Effects of Surface Modification on Bioactivity", Weis, R. P.; Montchamp, J.-L.; Coffer, J. L.; Desai, T. A.; Atthia, D. G. Disease Markers 2002, 18, 159.

"Palladium-Catalyzed Hydrophosphinylation of Alkenes and Alkynes", Deprèle, S.; Montchamp, J.-L. J. Am. Chem. Soc. 2002, 124, 9386.

"Palladium-Catalyzed Cross-Coupling Reaction of Anilinium Hypophosphite With Alkenyl Bromides and Triflates: Application to the Synthesis of GABA Analogs", Dumond, Y. R.; Montchamp, J.-L. J. Organomet. Chem. 2002, 653, 252.

"A Novel and Convenient Preparation of Hypophosphite Esters", Deprèle, S.; Montchamp, J.-L. J. Organomet. Chem. 2002, 643-644, 154.

"Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins: Synthesis of Monosubstituted Phosphinic Acids and Esters", Deprèle, S.; Montchamp, J.-L. J. Org. Chem. 2001, 66, 6745.

"Synthesis of Monosubstituted Phosphinic Acids: Palladium-Catalyzed Cross-Coupling Reactions of Anilinium Hypophosphite", Montchamp, J.-L.; Dumond, Y. R. J. Am. Chem. Soc. 2001, 123, 510.

"Orthosilicate-Mediated Esterification of Monosubstituted Phosphinic Acids", Dumond, Y. R.; Baker, R. L.; Montchamp, J.-L. Org. Lett. 2000, 2, 3341.