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Faculty Research

Knapp, Spencer

SK cvpictureProfessor

Research Synopsis: Total synthesis of natural products and the development of new synthetic methods

Phone: (848) 445-2627




Research Summary

My research interests are in synthetic organic chemistry, including the development of new synthetic methods and the synthesis of natural products. Over the last 36 years we have developed methods for the stereoselective functionalization of alkenes, the construction of a variety of nitrogen and sulfur containing heterocycles, and the selective synthesis and transformation of carbohydrates and nucleosides. Methods for the oxido-accelerated retro-Diels-Alder reaction, "iodolactamization", carboxylate selenonation, and the N-benzoylcarbamate and carbonimidothioate cyclizations were developed in these labs. We have applied this chemistry to the synthesis of approximately 20 natural products, including slaframine, tetrahydropseudodistomin, capuramycin, trehazolin, conduritol A, rosmariquinone, the shimofuridin nucleoside disaccharide, the protein kinase C inhibitor penazetadine, the ezomycin nucleoside disaccharide, the sialidase inhibitor siastatin B, the adenosine phosphodiesterase inhibitor griseolic acid B, the liposidomycin diazepanone nucleoside, and the M. tuberculosis detoxifier mycothiol. In other recent work, we have built and characterized porphyrin and chlorin dimers to help understand the structure and photophysics of the bacterial and plant photosystems, have investigated new syntheses, transformations, mechanisms, and applications of thioglycosides and seleninates, and have designed novel glycosidase inhibitors as a means to elucidate enzyme function and mechanism.

Current Work

SKnapp current workPresent synthetic targets include the nucleoside antibiotics griseolic acid A and liposidomycin B. We are also pursuing the discovery, optimization, and efficient synthesis of new antimalarial agents, as well as new methods for drug delivery and controlled release.



Recent Publications

Spencer Knapp. "The Tethered Nitrogen in Natural Products Synthesis" Chem. Soc. Rev. 1999, 28, 61.

Robert T. Stibrany, Spencer Knapp, Joseph A. Potenza, and Harvey J. Schugar. "The Product of a Novel Aminalization, Bis[bis(3,5-dimethylpyrazol-1-yl)(dimethylamino)methane]copper(II) perchlorate · Bis(dichloromethane)" Inorg. Chem. 1999, 38, 132.

Spencer Knapp and Krishnan Malolanarasimhan. "Oligomeric Thioglycosides with alpha-D-manno-(1'->2) Linkages from a Glycal-1,2-Episulfide" Org. Lett . 1999, 1, 611.

Spencer Knapp, Buwen Huang, Thomas J. Emge, Suzie Sheng, Karsten Krogh-Jespersen, Joseph A. Potenza, and Harvey J. Schugar. "A Pyropheophorbide Dimer with Single Pyrrole pi Overlap and a Low-Energy Q Absorption" J. Am. Chem. Soc. 1999, 121, 7977.

Spencer Knapp and Vijay K. Gore. "Synthesis of the Ezomycin Nucleoside Disaccharide" Org. Lett. 2000, 2, 1391.

Stephen Fox, Robert T. Stibrany, Joseph A. Potenza, Spencer Knapp, and Harvey J. Schugar. "Copper (II) and Nickel (II) Complexes of Binucleating Macrocyclic Bis(disulfide)tetramine Ligands" Inorg. Chem. 2000, 39, 4950.

Joseph A. Potenza, Thomas J. Emge, Jennifer Albaneze, Spencer Knapp, and Harvey J. Schugar. "A Spiro-linked Pyrene-naphthoquinone" Acta Cryst. 2000, C56, 1494.

Spencer Knapp and Dalian Zhao. "Synthesis of the Sialidase Inhibitor Siastatin B" Org. Lett. 2000, 2, 4037.

J. B. Lu, Z. P. Chen, Y. P. Yan, Spencer Knapp, Harvey Schugar, and Kuang-Yu Chen. "Aminohexanoic Hydroxamate is a Potent Inducer of the Differentiation of Mouse Neuroblastoma Cells" Cancer Lett. 2000, 160, 59.

Brian Mark, David J. Vocadlo, Spencer Knapp, Barbara L. Triggs-Raine, Stephen G. Withers, and Michael N. G. James. "Crystallographic Evidence for Substrate-assisted Catalysis in a Bacterial beta-Hexosaminidase" J. Biol. Chem. 2001, 276, 10330.

Spencer Knapp and David S. Myers. "alpha-GlcNAc Thioconjugates" J. Org. Chem. 2001, 66, 3636.

Spencer Knapp, Gregori J. Morriello, Santosh R. Nandan, Thomas J. Emge, George A. Doss, and Lijian Chen. "Assignment of the Liposidomycin Diazepanone Stereochemistry" J. Org. Chem. 2001, 66, 5822.

Spencer Knapp, Machender R. Madduru, Zhijian Lu, Gregori J. Morriello, Thomas J. Emge, and George A. Doss. "Synthesis of Griseolic Acid B by pi-Face-Dependent Radical Cyclization" Org. Lett. 2001, 3, 3583-3585.

Brian L. Mark, David J. Vocadlo, Dalian Zhao, Spencer Knapp, Stephen G. Withers, and Michael N. G. James. "Biochemical and Structural Assessment of the 1-N-Azasugar GalNAc-isofagomine as a Potent Family 20 beta-N-acetylhexosaminidase Inhibitor" J. Biol. Chem. 2001, 276, 42131-42137.

Spencer Knapp, Gregori J. Morriello, and George A. Doss. "Synthesis of the Liposidomycin Diazepanone Nucleoside" Org. Lett. 2002, 4, 603.

Spencer Knapp and David S. Myers. "Synthesis of alpha-GalNAc Thioconjugates from an alpha-GalNAc Mercaptan" J. Org. Chem. 2002, 67, 2995.

Spencer Knapp, Gregori J. Morriello, and George A. Doss. "A Stevens Rearrangement Thwarts Glycosylation with Liposidomycin Diazepanone Ribofuranosyl Donors" Tetrahedron Lett. 2002, 43, 5797.

Spencer Knapp and Etzer Darout. "The Surprise Synthesis of alpha-GlcNAc 1-C-Sulfonates" Tetrahedron Lett. 2002, 43, 6075.

Spencer Knapp, Chunhua Yang, and Thomas Haimowitz. "Addition of Trialkylaluminium Reagents to Glyconolactones. Synthesis of 1-C-Methyl GlcNAc Oxazoline and Thiazoline" Tetrahedron Lett. 2002, 43, 7101.

Spencer Knapp, Silvia Gonzales, David S. Myers, Lisa L. Eckman, and Carole A. Bewley. "A Shortcut to Mycothiol Analogues" Org. Lett. 2002, 4, 4337.

Spencer Knapp, Gregori J. Morriello, and George A. Doss. "Stereoselective Ring Contraction Diverts the Mitsunobu Reaction of a 6-Hydroxy-1,4-diazepan-2-one" Tetrahedron Lett. 2003,44, 2645.

Thomas J. Emge, Matthew J. Clements, David S. Myers, and Spencer Knapp. "(5-Bromopyrrol-3-yl) cyclohexylmethanone" Acta Cryst, 2003, E59, 1.

Brian L. Mark, Don J. Mahuran, Maia M. Cherney, Dalian Zhao, Spencer Knapp, and Michael N. G. James. "Crystal Structure of Human Hexosaminidase B: Understanding the Molecular Basis of Sandhoff and Tay-Sachs Disease" J. Mol. Biol. 2003, 327, 1093.

Zhang, X.; Fried, A.; Knapp, S.; Goldman, A. S. "Novel Synthesis of Enamines by Iridium-Catalyzed Dehydrogenation of Tertiary Amines" Chem. Commun. 2003,2060.

Spencer Knapp and Brian A. Kirk. "Glycosylation with 2'-Thio-S-acetyl Participation" Tetrahedron Lett. 2003, 44, 7601.

Spencer Knapp, Benjamin Amorelli, and George A. Doss. "A Fused GalNAc-thiazole from a Singular and Unanticipated Fragmentation" Tetrahedron Lett. 2004, 45, 8507.

Spencer Knapp and Etzer Darout. "New Reactions of Selenocarboxylates" Org. Lett. 2005, 7, 203.

Spencer Knapp, Benjamin Amorelli, Etzer Darout, Christian C. Ventocilla, Lawrence M. Goldman, Richard A. Huhn, and Ellen C. Minnihan. "A Family of Mycothiol Analogues" J. Carbohydr. Chem. 2005, 24, 103.

Spencer Knapp, Chunhua Yang, Srihari Pabbaraja, Brian Rempel, Steven Reid, and Stephen G. Withers. "Synthesis and Kinetic Analysis of the N-Acetylhexosaminidase Inhibitor XylNAc-Isofagomine" J. Org. Chem. 2005, 70, 7715.

Spencer Knapp, Richard C. Huhn, and Benjamin Amorelli. "Thionation: GlcNAc-Thiazoline Triacetate {(3aR,5R,6S,7R,7aR)-5-Acetoxymethyl-6,7-diacetoxy-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole}" Org. Synth. 2007, 84, 68.

Spencer Knapp, Etzer Darout, and Benjamin Amorelli. "New Glycomimetics: Anomeric Sulfonates, Sulfenamides, and Sulfonamides" J. Org. Chem. 2006, 71, 1380.

Spencer Knapp, Vinay V. Thakur, Machender R. Madduru, Krishnan Malolanarasimhan, Gregori J. Morriello, and George A. Doss. "Short Synthesis of Octosyl Nucleosides" Org. Lett. 2006, 7, 1335.

Robert T. Stibrany, Chengmin Zhang, Thomas J. Emge, Harvey J. Schugar, Joseph A. Potenza, and Spencer Knapp. "A Tris(pyrazolyl) Arene Ligand That Selects Cu(I) over Cu(II)" Inorg. Chem. 2006, 45, 9713.

Spencer Knapp and Kehinde Ajayi. "The Anomeric Pudovik Rearrangement" Tetrahedron Lett. 2007, 48, 1945.

Spencer Knapp and Younong Yu. "Synthesis of the Oxygenated Pactamycin Core" Org. Lett. 2007, 8, 1359.

Spencer Knapp, Mohannad Abdo, Kehinde Ajayi, Richard C. Huhn, Thomas J. Emge, Eun Ju Kim, and John A. Hanover. "Tautomeric Modifications of GlcNAc-Thiazoline" Org. Lett. 2007, 9, 2321.

Eun J. Kim, Benjamin Amorelli, Mohannad Abdo,Craig J. Thomas, Dona C. Love, Spencer Knapp, and John A. Hanover. "Distinctive Inhibition of OGA Isoforms by an alpha-GlcNAc Thiolsulfonate" J. Am. Chem. Soc. 2007, 129, 14854.

Alexander Gosslau, Srihari Pabbaraja, Spencer Knapp, and Kuang Yu Chen. "Trans- and Cis-Stilbene Polyphenols Induced Rapid Perinuclear Mitochondrial Clustering and p53-Independent Aptosis in Cancer Cells But Not Normal Cells" Eur. J. Pharmacol. 2008, 587, 25.

Benjamin Amorelli, Chunhua Yang, Brian Rempel, Stephen G. Withers, and Spencer Knapp. "N-Acetylhexosaminidase Inhibitory Properties of C-1 Homologated GlcNAc- and GalNAc-Thiazolines" Bioorg. Med. Chem. Lett. 2008, 18, 2944.

Mohannad Abdo and Spencer Knapp. "Biomimetic Seleninates and Selenonates" J. Am. Chem. Soc. 2008, 130, 9234.

Chad Slawson, T. Lakshmanan, Spencer Knapp, and Gerald W. Hart. "A Mitotic GlcNAcylation/Phosphorylation Signaling Complex Alters the Post-Translational State of the Cytoskeletal Protein Vimentin" Mol. Biol. Cell 2008, 19, 4130.

Mohannad Abdo,Sijiu Liu, Bo Zhou, Chad D. Walls, Spencer Knapp, and Zhong-Yin Zhang. "Seleninate in Place of Phosphate: Irreversible Inhibition of Protein Tyrosine Phosphatases" J. Am. Chem. Soc. 2008, 130, 13196.

Spencer Knapp, David Fash, Mohannad Abdo, Thomas J. Emge, and Paul R. Rablen. "GlcNAc-Thiazoline Conformations" Bioorg. Med. Chem. 2009, 17, 1831.

James M. Macdonald, Chris A. Tarling, Edward J. Taylor, Rebecca J. Dennis, David S. Myers, Spencer Knapp, Gideon J. Davies, and Stephen G. Withers. "Chitinase Inhibition by Chitobiose and Chitotriose Thiazolines" Angewandte Chem. Internat. Ed. Engl. 2010, 49, 2599.

Kehinde Ajayi, Vinay V. Thakur, Robert C. Lapo, and Spencer Knapp. “Intramolecular alpha-Glucosaminidation: Synthesis of Mycothiol” Org. Lett. 2010, 12, 2630.

Mohannad Abdo, Zong Zhang, Vern L. Schramm, and Spencer Knapp. “Electrophilic Aromatic Selenylation: New OPRT Inhibitors” Org. Lett. 2010, 12, 2982.

Eun Ju Kim, Dona C. Love, Etzer Darout, Mohannad Abdo, Brian Rempel, Stephen G. Withers, Paul R. Rablen, John A. Hanover, and Spencer Knapp. “OGA Inhibition by GlcNAc-selenazoline” Bioorg. Med. Chem. 2010, 18, 7058.

Mohannad Abdo and Spencer Knapp. “Mechanism of a Redox Coupling of Seleninic Acid with Thiol” J. Org. Chem., 2012, 77, 3433.

Walter S. Won and Spencer Knapp. “Β-D-Arabinosyl 1-C-Sulfonic Acid” J. Sulfur Chem. 2013, 34, 33. DOI:10.1080/17415993.2012.7068

Mohannad Abdo, Zhexun Sun and Spencer Knapp. “Biohybrid -Se-S- Coupling Reactions of an Amino Acid Derived Seleninate” Molecules 2013, 18, 1963; DOI:10.3390/molecules18021963

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