Organic

Donald A. Tomalia

Photo: 
First Name: 
Donald A.
Last Name: 
Tomalia
Official Title: 
Adjunct Professor of Chemistry

Dr. Tomalia received his B.A. in chemistry from the University of Michigan and while at The Dow Chemical Company completed his Ph.D.

Education: 
  • B.A. University of Michigan
  • Ph.D. Michigan State University
Other Affiliations: 

National Dendrimer Center at Central Michigan University

Inaugural Aldrich Distinguished Lecture

Mon, 2012-10-15 16:00
Speaker: 

Stephen L. Buchwald
Camille Dreyfus Professor of Chemistry
Massachusetts Institute of Technology

Location: 

Carolyn Lynch Lecture Hall

Palladium-Catalyzed Carbon-Nitrogen and Carbon-Carbon Bond-Forming Reactions: Progress, Applications and Mechanistic Studies

Michael Rubinstein, University of North Carolina, Chapel Hill; Polymer Seminar

Thu, 2012-10-18 09:00 - 10:30

Location: Carolyn Hoff Lynch Room

Geraldine Masson; Organic Seminar

Mon, 2012-10-08 08:00 - 09:30

Location: Carolyn Hoff Lynch Room

Reinhard Brueckner, Institute for Organic Chemistry and Biochemistry; Organic Seminar

Mon, 2012-10-01 08:00 - 09:30

Location: Carolyn Hoff Lynch Room

Hien Nguyen, U of Iowa; Organic Seminar

Mon, 2012-09-17 08:00 - 09:30

location: Carolyn Hoff Lynch Room

hosted by: Gary Molander

 

Jeffrey D. Winkler

Photo: 
First Name: 
Jeffrey D.
Last Name: 
Winkler
Official Title: 
Merriam Professor of Chemistry

Organic Chemistry 

Contact Information
Office Location: 
449 Chemistry Bldg.
Email: 
winkler@sas.upenn.edu
Phone: 
(215) 898-0052
Fax: 
(215) 573- 6329
Admin Support: 
Education: 
  • A.B. Harvard College (1977)
  • M.A., M.Phil., Ph.D. Columbia University (1981-83)
Research Interests: 

New Synthetic Pathways Based on the Intramolecular Dioxenone and Vinylogous Amide Photocycloaddition Reactions

We have developed these methods and have applied them to the first total syntheses of several molecules of biological importance, including manzamine A, 1, saudin, 2 , and ingenol, 3.

 

Total Synthesis of Manzamine-Related Structures

Current efforts in our laboratory are focused toward the synthesis of nakadomarin, 4, a structurally complex hexacyclic alkaloid that displays a range of promising biological activities including cytotoxic activity against murine lymphoma L1210 cells, inhibitory activity against cyclin dependent kinase 4, and anti-microbial activity against a fungus and a Gram-positive bacterium. We have also demonstrated that manipulation of the structure of 1 via Grubbs metathesis leads to the formation of novel structures, i.e., 5, with antibacterial properties comparable to those of ciprofloxacin. Finally, we have embarked on a program directed toward the synthesis of neokauluamine, 6, a dimeric manzamine with highly potent immunosuppressive properties. 

 

Transformations Using Organic Photochemistry

We have recently discovered a novel approach to the synthesis of substituted thiophenes 8 from arylsulfide enone precursors 7. The study of the mechanism of this unusual transformation (9 is a byproduct) as well as its application to the synthesis of more complex structures is currently underway in our laboratory.

 

Development of Novel Inhibitors of Hedgehog Signaling Based on Cyclopamine

Aberrant activation of the Sonic Hedgehog (Hh) signaling pathway has been associated with numerous malignancies in the brain, breast, pancreas and other organs. In vivo evidence suggests the antagonism of excessive Hh signaling may provide a route to unique mechanism-based therapies for the treatment of cancer. The steroidal alkaloid cyclopamine 10 suppresses the Hh signaling pathway, and has recently been been shown to be effective in the treatment of cancer using a variety of mouse models. Human cells are also sensitive, supporting the promising use of this natural product. However, the metabolic instability of cyclopamine precludes its clinical use. A significant demand exists for more stable cyclopamine-like structures. This project is directed toward the synthesis of cyclopamine-like structures, i.e., 11, from readily available metabolically-stable steroidal precursors, i.e., estrone.

 

Total Synthesis of Cortistatin A

The development of specific anti-angiogenic agents that could serve as anticancer chemotherapeutic agents is an important goal. In 2006, Kobayashi isolated the cortistatins from the marine sponge Corticium simplex. Cortistatin A 12 is the most active member of this family. It exhibits antiproliferative activity against human umbilical vein endothelial cells at nM concentrations. The total synthesis of the cortistatins and designed materials with cortistatin-like properties is one of the goals of our laboratory.

Patrick J. Walsh

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First Name: 
Patrick J.
Last Name: 
Walsh
Official Title: 
Professor of Chemistry

Inorganic Chemistry, Organic Chemistry, Chemical Catalysis

Contact Information
Office Location: 
3001 IAST
Email: 
pwalsh@sas.upenn.edu
Phone: 
(215) 573-2875
Fax: 
(215) 573-6743
Admin Support: 
Education: 
  • Advisor Prof. K. Barry Sharpless
  • 1986 B.A. in Chemistry, University of California, San Diego
  • 1991 Ph.D in Chemistry, University of California, Berkeley
  • 1991-1994 NSF Postdoctoral Fellow Postdoctoral, The Scripps Research Institute
Research Interests: 

Research in the Walsh group merges the fields of catalysis and organic and inorganic synthesis with the goal of achieving new catalytic asymmetric transformations for the synthesis of chiral building blocks. The transformations we have chosen to study are asymmetric C-C and C-O bond forming reactions, because construction of these bonds lies at the very heart of organic synthesis. We are also interested in the development of tandem reactions that combine several steps in a single reaction vessel. By introducing tandem reactions, we can increase synthetic efficiency while reducing the number of purification steps necessary. 

 

Shown below are examples of tandem reactions developed in the Walsh group:

 

We are also interested in reaction mechanisms, which gives us the opportunity to synthesize some interesting catalysts. Shibasaki's M3(THF)n(BINOLate)3Ln (Ln = lanthanide, M = Li, Na, K) catalyst are among the most efficient known in asymmetric catalysis. We have studied the structure and reactivity of these amazing catalysts, one of which is shown below.4-6 

We are also interested in structural organozinc chemistry. The first example of zinc coordinated to C-C double bond was recently reported from our group.7 

In 2006 the Walsh group crystallographically characterized about 40 compounds, most of which contained metals.

Edward R. Thornton

Photo: 
First Name: 
Edward R.
Last Name: 
Thornton
Official Title: 
Emeritus Professor of Chemistry

Organic and Bioorganic Chemistry 

Contact Information
Office Location: 
Senior Faculty Suite
Email: 
ert@sas.upenn.edu
Phone: 
(215) 898-8309
Education: 
  • B.A. Syracuse University (1957)
  • Ph.D. Massachusetts Institute of Technology (1959)
  • N. I. H. Postdoctoral Fellow, M.I.T. (1959-1960)
  • N.I.H. Postdoctoral Fellow, Harvard University (1960-1961)
Research Interests: 

Research has recently focused on computational studies involving molecular interactions and selectivity, molecular architecture, and molecular recognition. Some of our most recent research has involved collaborations with Professors Ralph Hirschmann and Amos B. Smith, III (University of Pennsylvania) on electrostatic potentials as a means of understanding somatostatin receptor interactions, and with Professor Nobuo Tanaka (Kyoto Institute of Technology) on isotope effects in HPLC as a means of studying hydrophobic effects and interactions.

 

We have found substantial differences in electrostatic potential surfaces (shown in 1 and 2) between different aromatic systems such as benzene (1) vs. pyridine (2). These differences correlate nicely with binding properties of glucose-based peptidomimetics containing different aromatic substituents, and they appear to explain observed differences in binding to the somatostatin receptor.

 

We have studied the separation of hydrogen/deuterium isotopologue pairs by means of reversed-phase chromatographic separation in order to examine deuterium isotope effects on hydrophobic binding. The results (see Figure, where tr is the HPLC retention time) demonstrate that dispersion interactions in the hydrophobic phase are an important component of hydrophobic interactions.

 

We are also interested in design of extended three-dimensional structures with specific architectures and novel properties. Large molecules with architecturally complex structures and shapes, having properties designed for specific purposes, are of increasing importance in all areas of organic and bioorganic chemistry.

 

A major area of interest in our lab has been study of interactions, transition structures, and mechanisms, for example, mechanistic studies on deuterium and sulfur isotope effects, solvolysis reactions, E2 eliminations, mass spectra, electrical discharge reactions, acid-base catalysis, the Diels-Alder reaction, theory of transition state structural effects, and reactions of carbenes.

 

Previous bioorganic studies in our lab involved structures and interactions of saccharides and glycolipids utilizing 13C NMR relaxation times, hydrophobic interactions, carbene photochemical labeling of model membranes, and proteins of synaptic vesicles.

Amos B. Smith III

Photo: 
First Name: 
Amos B.
Last Name: 
Smith III
Official Title: 
Rhodes-Thompson Professor of Chemistry

Organic Chemistry

Contact Information
Office Location: 
440N
Email: 
smithab@sas.upenn.edu
Phone: 
(215) 898-4860
Fax: 
(215) 898-5129
Admin Support: 
Education: 
  • B.S.- M.S. Bucknell University (1966)
  • Ph.D. Rockefeller University (1972)
  • Associate, Rockefeller University (1972-73)
Research Interests: 

Smith's research interests encompass three diverse areas: natural product synthesis, bioorganic chemistry and materials science. To date, more than 90 architecturally complex natural products having significant bioregulatory properties have been prepared in his Laboratory. In addition, Smith, in collaboration with Ralph Hirschmann, has achieved the design and synthesis of non-peptide peptidomimetics of neuropeptideic hormone/transmitters and protease enzyme inhibitors and, also with Stephen Benkovic (Penn State), haptens for the production of catalytic antibodies capable of peptide bond formation. At Monell, in collaboration with Peter Jurs (Penn State), he pioneered the use of computerized pattern recognition techniques for the analysis of primate chemical communication. Collaborative programs at the LRSM include the chemistry and physics of novel liquid crystals and the fullerenes. To date Smith research achievements have been reported in more than 500 peer reviewed publications.

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

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