|Office:||Flanner Hall 215 1068 W. Sheridan Road Chicago, IL 60660|
Ph.D. in Chemistry, Indiana University, Bloomington, IN
B.A. in Chemistry, Kalamazoo College, Kalamazoo, MI
Supramolecular chemistry involves the formation of complex molecular entities that have the capacity to participate in specific molecular recognition of guest molecules. Cyclophanes are supramolecular structures comprised of aromatic units with bridging chains forming cage-like structures and have found applications in molecular recognition as synthetic receptors, as models for intercalation, as building blocks for organic catalysts, and in the design of new pharmaceuticals. We are interested in the preparation and host-guest properties of apex-modified derivatives of cyclotriveratrylene (CTV). The crown-shaped cyclophane CTV (hexamethoxytribenzocyclononene), has been employed extensively as a scaffold in supramolecular chemistry.
We have found that the Beckmann rearrangement performed on pure CTV oxime crown conformer proceeds in high yield depending upon conditions chosen either to the expected 10-membered ring amide, or to a helical pentacyclic molecule derived from electrophilic aromatic addition to the cationic nitrilium intermediate. The ring-expanded amide exists at room temperature exclusively as the crown conformation based on the geminal coupling observed in the proton NMR [4.67 (1H, d, J = 15.0 Hz), 4.44 (1H, d, J = 15.3 Hz), 3.70 (1H, d, J =15.0 Hz), 3.56 (1H, d, J = 15.3 Hz)].
Curiously, the N-actylated Beckmann lactam
We followed the equilibration of the saddle conformer of CTV oxime to the corresponding crown conformer by 1H NMR in five separate solvents and determined the kinetic and thermodynamic parameters of the interconversion. The oxime saddle conformers of 3 are favored in CDCl3 (Keq = [saddle]/[crown] = 1.4), whereas the CTV oxime crown conformer 3a is favored in three more polar solvents studied (DMSO-d6, acetonitrile-d3, acetone-d6). Surprisingly, the CTV oxime crown conformer is also slightly favored in the non-polar solvent 1,4-dioxane-d8.
Recently, we have synthesized the dimethyl derivative of 5,10-dimethyl-10,15-dihydro-5H-tribenzo[b,e,h][1,4,7]triazonine ("N3-CTV") which is a new supramolecular scaffold related to cyclotriveratrylene (CTV).
dimethyl-N3-CTV dimethyl-N3-CTV X-ray Crystal Structure
We are also interested in the preparation of new cyclobutanone amino acid derivatives. that will be useful as peptidomimetics and modular protease inhibitors that can be tuned for inhibition of specific protease targets through elaboration of the core cyclobutanone with substituents to mimic a targeted endogenous peptide protease substrate for the treatment of various protease-dependent diseases including malaria, AIDS, cancer, and Alzheimer's disease. As novel conformationally constrained amino acid derivatives, these targets have broad general utility as peptidomimetics and beta-strand mimetics.
We have recently synthesized 2,4-disubstituted cyclobutanone deratives which are of interest as P-P' spanning serine protease inhibitors.
Marlon R. Lutz Jr., Matthias Zeller, Samuel Sarsah, Artur Filipowicz, Hailey Wouters, and Daniel P. Becker, “Synthesis, Crystal Structure, and Rearrangements of ortho-Cyclophane Cyclotetraveratrylene (CTTV) Tetraketone”, Supramolecular Chemistry, 2012, in press.
Othman A. Hamed, Arab El-Qisairi, Hanan Qaseer, Emad M. Hamed, Patrick M. Henry, and Daniel P. Becker, Asymmetric a-Hydroxy Ketone Synthesis by Direct Ketone Oxidation Using a Bimetallic Palladium(II) Complex”, Tetrahedron Lett., 2012, 53, 10.1016/j.tetlet.2012.03.066.
Osner, Zachary; Nyamjav, Dorjderem; Holz, Richard; Becker, Daniel P. “Direct Patterning of a Cyclotriveratrylene (CTV) Derivative for Directed Self-Assembly of C60“. Nanotechnology, 2011, 22, 275611.
Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Easton, Alan M.; Hockerman, Susan L.; Kiefer, James; Munie, Grace E.; Mathis, Karl J.; Li, Madeleine H.; Rico, Joseph G.; Villamil, Clara I.; Williams, Jennifer M. “MMP-13 Selective a-Sulfone Hydroxamates: A Survey of P1’ Heterocyclic Amide Isosteres” Bioorganic & Medicinal Chemistry Letters, 2011, 21 2820-2822.
Fobian, Yvette; Freskos, John N.; Barta, Thomas E.; Heintz, Robert; Kiefer, James R.; Mischke, Brent V.; Mullins, Patrick; Munie, Grace E.; Becker, Daniel P. “MMP-13 Selective a-Sulfone Hydroxamates Identification of selective P1’ Amides” Bioorganic & Medicinal Chemistry Letters, 2011, 21 2823-2825.
Hamed, Othman; Henry, Patrick; Becker, Daniel P. “Palladium(II)-Catalyzed Dicarboxymethylation of Chiral Allylic Alcohols: Chirality Transfer Affording Optically Active Diesters Containing Three Contiguous Chiral Centers“ Tetrahedron Lett., 2010, 51, 3514-3517.
Stephen A. Kolodziej, Susan L. Hockerman, Gary A. DeCrescenzo, Joseph J. McDonald, Debbie A. Mischke, Grace E. Munie, Theresa R. Fletcher, Nathan W. Stehle, Craig Swearingen and Daniel P. Becker “MMP-13 Selective Isonipecotamide alpha-Sulfone Hydroxamates” Bioorganic & Medicinal Chemistry Letters, 2010, 20 3561-3564.
Stephen A. Kolodziej, Susan L. Hockerman, Terri L. Boehm,, Joseph G. Rico, Jeffery N. Carroll, Gary A. De Crescenzo, Joseph J. McDonald, Debbie A. Mischke, Grace E. Munie, Theresa R. Fletcher, Nathan W. Stehle, Craig Swearingen and Daniel P. Becker, “Orally Bioavailable Dual MMP-1/MMP-14 Sparing MMP-13 Selective alpha-Sulfone Hydroxamates” Bioorganic & Medicinal Chemistry Letters, 2010, 20 3557-3560.
French, David; Lutz, Marlon R.; Lu, Chichi; Zeller, Matthias; Becker, Daniel P. “A Thermodynamic and Kinetic Characterization of the Solvent Dependence of the Saddle-Crown Equilibrium of Cyclotriveratrylene (CTV) Oxime, J. Phys. Chem A., 2009, 113, 8258-8267.
Zeller, Matthias; Lutz Jr., Marlon R.; Becker, Daniel P. “An aza-cyclophane stacked in racemic columnar assemblies: Whole molecular disorder in a 2D solid solution“ Acta Cryst B: Structural Science 2009, 65(2), 223-229. PMID: 19299878
Lutz Jr., Marlon R.; Zeller, Matthias; Becker, Daniel P. "Beckmann Rearrangement of Cyclotriveratrylene (CTV) Oxime: Tandem Beckmann-Electrophilic AromaticAddition", Tetrahedron Letters 2008, 49, 5003-5005.
Armoush, Nicola; Kataria, Preeti; Becker, Daniel P. "Synthesis of Substituted 2-Amino-Cyclobutanones", Synthetic Communications 2008, 38 (11), 1679-1687.
Lutz Jr., Marlon R., Zeller, Matthias; Becker, Daniel P. "2,3,5',6,6',7-hexamethoxy-3'H,10H-spiro[anthracene-9,1'-isobenzofuran]-3',10-dione", Acta Cryst. 2007, 63o4390-o4391.
Lutz Jr., Marlon R., Zeller, Matthias; Becker, Daniel P. "2,3,8,12,13-Pentamethoxy-5H-dibenzo[c,n]acridin-7(6H)-one", Acta Cryst. 2007, E63, o3857-o3858.
Lutz Jr., Marlon R., French, David C., Rehage, Peter, & Becker, Daniel P. "Isolation of the saddle and crown conformers of cyclotriveratrylene (CTV) oxime", Tetrahedron Lett. 2007, 48, 6368-6371.
Department of Chemistry
Flanner Hall 215
1032 W. Sheridan Road
Chicago, IL 60660
Phone: (773)508-3089 or (773)508-3100
Courier shipments (UPS, FEDEX etc) to:
1068 W. Sheridan Road
Chicago IL 60660