FUNDING: we gratefully acknowledge the following for the current financial support of our research:
The National Science Foundation
Our group's research interests are in the areas of organophosphorus chemistry, and bioorganic/medicinal chemistry. The element phosphorus is the common thread throughout our research projects. The core of our program in phosphorus-based 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 (such as peptide nucleic acids (PNAs)/phosphinate hybrids). We are also interested in 1,1-bisphosphorus compounds as pyrophosphate analogs, since pyrophosphate has a rich biochemical role. Finally, other investigations aiming at the modulation of GABA receptors with phosphinic analogues are relevant to the treatment of various central nervous system (CNS) disorders. With TCU’s Professor Coffer, we have also been preparing and evaluating components for biocompatible calcified nanoporous. In general, because phosphorus compounds are ubiquitous in living systems, the synthesis of phosphorus-containing mimics can have important medicinal benefits. Our second research interest concerns organophosphorus chemistry and is driven by several main objectives: firstly, the development of P-chiral ligands to be ultimately used in catalytic asymmetric transformations, including transition metal-catalyzed reactions; secondly, the building of a methodology to produce phosphorus compounds in general; and thirdly, the preparation of compounds possessing potential biological activity. Our expertise lies in the area of hypophosphorous compounds and their derivatives (H-phosphinates and phosphinates, and to a lesser extent phosphonates). One area of significant current interest in the laboratory, is the development of sustainable synthetic methodologies to avoid phosphorus trichloride (PCl3). Our program toward the development of new methodology for the synthesis of phosphinic acids has led to many 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 also applied to the synthesis of biologically active compounds, to the preparation of intermediates with industrial value, and to the preparation of P-chiral building blocks. Combining the above research directions into 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 are required, which borrow from independently developed methodologies. In general, a combination of organic synthesis, methodology, and chemical biology, is used to pursue our objectives.
General Synthesis of P-Stereogenic Compounds: The Menthyl Phosphinate Approach Berger, O.; Montchamp, J.-L. Org. Biomol. Chem. 2016, 14, 7552-7562.
P(=O)H to P-OH Tautomerism: A Theoretical and Experimental Study Janesko, B. J.; Fisher, H. C.; Bridle, M. J.; Montchamp, J.-L. J. Org. Chem. 2015, 80, 10025-10032.
Development of a New Family of Chiral Auxiliary Gelat, F.; Richard, V.; Berger, O; Montchamp, J.-L. Org. Lett. 2015, 17, 1819-1821.
Manganese-Mediated Alkene Chloro-Phosphinoylation Richard, V.; Fisher, H. C.; Montchamp, J.-L. Tetrahedron Lett. 2015, , online.
Carbon-Hydrogen to Carbon-Phosphorus Transformations Montchamp, J.-L. Top. Curr. Chem. 2015, 361, 217-252.
Synthesis of (phosphonomethyl)phosphinate pyrophosphate analogues via the phospha-Claisen condensation Gelat, F.; Lacomme, C.; Berger, O; Gavara, L.; Montchamp, J.-L. Org. Biomol. Chem. 2015, 13, 825-833.
"Radical Arylation of H-Phosphinates and Related Compounds Berger, O.; Montchamp, J.-L. Chem. Eur. J. 2014, 20 , 12385.
Phosphinate-Containing Heterocycles: a Mini-Review Berger, O.; Montchamp, J.-L. Beilstein J. Org. Chem. 2014, 10 , 732.
Manganese-Catalyzed and Promoted Reactions of H-Phosphinate Esters Fisher, H. C.; Berger, O.; Gelat, F. Montchamp, J.-L. Adv. Synth. Catal. 2014, 356 , 1199.
Phosphinate Chemistry in the 21st Century: A Viable Alternative to the Use of Phosphorus Trichloride in Organophosphorus Synthesis Montchamp, J.-L. Acc. Chem. Res. 2014, 47, 77
Organophosphorus Chemistry Without PCl3: A Bridge From Hypophosphorous Acid to H-Phosphonate Diesters Fisher, H. C.; Prost, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2013, ,7973.
A General Strategy for the Synthesis of P-Stereogenic Compounds Berger, O.; Montchamp, J.-L. Angew. Chem. Int. Ed. 2013, 52,11377. (HOT PAPER)
Hypophosphorous Acid, Second Update Gelat, F.; Montchamp, J.-L. Encyclopedia of Reagents for Organic Synthesis (eEROS) , ,
Phosphinic acid, P-(hydroxymethyl)- Berger, O..; Montchamp, J.-L. Encyclopedia of Reagents for Organic Synthesis (eEROS) , ,
Hydrophosphinylation of Unactivated Terminal Alkenes Catalyzed by Nickel Chloride Ortial, S.; Fisher, H. C.; Montchamp, J.-L. J. Org. Chem. 2013, 78, 6599
Phosphorus-Carbon Bond Formation: Palladium-Catalyzed Cross-Coupling of H-Phosphinates and Other P(O)H-Containing Compounds Berger, O.; Petit, C.; Deal E. L.; Montchamp, J.-L. Adv. Synth. Catal. 2013, 355, 1361
The Phosphorus-Claisen Condensation Gavara, L.; Gelat, F.; Montchamp, J.-L. Tetrahedron. Lett. 2013, 54, 817
Organophosphorus Synthesis Without Phosphorus Trichloride: The Case For The Hypophosphorous Pathway Montchamp, J.-L. Phosphorus, Sulfur and Silicon and the Related Elements 2013, 188, 66
DBU-Promoted Alkylation of Alkyl Phosphinates and H-Phosphonates Gavara, L.; Petit, C.; Montchamp, J.-L. Tetrahedron Lett. 2012, 53, 5000
Chemistry of the versatile (hydroxymethyl)phosphinyl P(O)CH2OH functional group Berger, O.; Gavara, L.; Montchamp, J.-L. Org. Lett. 2012, 14, 3404
Synthesis of Disubstituted Phosphinates via Palladium-Catalyzed Hydrophosphinylation of H-Phosphinic Acids Petit, C.; Fécourt, F.; Montchamp, J.-L. Adv. Synth. Catal. 2011, 353, 1883
Palladium-Catalyzed Cross-Coupling of H-Phosphinate Esters with Chloroarenes Deal, E. L.; Petit, C.; Montchamp, J.-L. Org. Lett. 2011, 13, 3270
Synthesis of Z-Alkenyl Phosphorus Compounds Through Hydroalumination and Carbocupration of Alkynyl Precursors Ortial, S.; Montchamp, J.-L. Org. Lett. 2011, 13, 3134
Silver-free synthesis of nitrate-containing room-temperature ionic liquids Smith, N. W.; Gourisankar, S. P.; Montchamp, J.-L.; Dzyuba, S. V. New. J. Chem. 2011, 35, 909
Regiocontrol in the Palladium-Catalyzed Hydrophosphinylation of Terminal Alkynes Belabassi, Y.; Bravo-Altamirano, K.; Montchamp, J.-L. J. Organomet. Chem. 2011, 696, 106
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, 75, 8166
Strategies for the asymmetric synthesis of H-phosphinate esters Bravo-Altamirano, K.; Coudray, L.; Montchamp, J.-L. Org. Biomol. Chem. 2010, 8, 5541
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 AlcoholsCoudray, 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.
Monoalkylation of Alkyl Phosphinates to Access H-Phosphinic Acid Esters
Reaction of Sodium Hypophosphite with Terminal Alkynes: Synthesis of 1,1-bis-H-Phosphinates
Phosphorus-Carbon Bond Formation: Cross-Coupling Reactions of Alkyl Phosphinates
with Aryl, Heteroaryl, Alkenyl, Benzylic, and Allylic Halides and Triflates
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,
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.
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