Martin J. O'Donnell, Ph.D.Chancellor's Professor Emeritus, Department of Chemistry & Chemical Biology
- B.S., University of Iowa, 1968
- Ph.D., Yale University, 1973
- Postdoctoral Fellow, Universite Catholique de Louvian, Belgium, 1973-75
We have developed methods for the solution-phase preparation of optically active unnatural a-amino acids by carbon-carbon bond-forming reactions. An early program in our lab led to the first catalytic enantioselective synthesis of amino acids by alkylation (alkyl group in red) reactions using "green catalysts" (those without a metal) derived from the Cinchona alkaloids. This chemistry utilizes the benzophenone imines of glycine esters, known as "O'Donnell Schiff bases." It has been used extensively by both academic and industrial scientists for the preparation of new and unusual amino acids and peptidomimetics on both small and industrial scale (see following example; 89 - 99.5% ee, 9 structurally diverse alkyl halides and Michael acceptors).
Since 1995 we have collaborated with Professor Bill Scott of our department for the preparation of unnatural a-amino acids by solid-phase synthesis. We have developed methodology for the synthesis of more than 40 different amino acid-based scaffolds, which allow "decoration" using common starting materials such as alkyl halides (grey or red), carboxylic acid derivatives (blue) and amines (green). The major steps involve allylation of a resin-bound monosubstituted amino acid derivative, acylation with an acid chloride and ozonolysis to the key on-resin aldehyde intermediate. Subsequent reaction with cysteine ethyl ester to the thiazolidine followed by heating results in a cyclitive cleavage to give the bicyclic product shown.
A second area of the Scott/O'Donnell collaboration has been the development and implementation of a research-based experience for the classroom called "Distributed Drug Discovery (D3). D3 is currently used in the second-semester organic chemistry laboratory (C344) and for IUPUI's undergraduate research students (C409). To date, more than 1,000 IUPUI undergraduates have participated in this program, which allows them to prepare and analyze amino acid-based potential drug candidates using solid-phase combinatorial synthesis. Examples of the scaffolds used are shown below:
Publications & Professional Activities
P. Zajdel, J. Krol, K. Grychowska, M. Pawlowski, G. Subra, G. Nomezine, J. Martinez, G. Satala, A. J. Bojarski, Z. Zhou, M. J. O'Donnell and W. L. Scott "Solid-phase synthesis of arylpiperazine derivatives and implementation of the Distributed Drug Discovery (D3) project in the search for CNS agents" Molecules 2011, 16, 4104-4121.
W. L. Scott, Z. Zhou, P. Zajdel, M. Pawlowski and M. J. O'Donnell "Solid-phase synthetic route to multiple derivatives of a fundamental peptide unit" Molecules 2010, 15, 4961-4983.
W. L. Scott, Z. Zhou, J. G. Martynow and M. J. O'Donnell "Solid-phase synthesis of amino- and carboxyl-functionalized unnatural a-amino amides" Org. Lett. 2009, 11, 3558-3561.
J. E. Green, D. M. Bender, S. Jackson, M. J. O'Donnell and J. R. McCarthy "Mitsunobu approach to the synthesis of optically active a,a-disubstituted amino acids" Org. Lett. 2009, 11, 807-810.
W. L. Scott and M. J. O'Donnell "Distributed Drug Discovery, part 1: Linking academia and combinatorial chemistry to find drugs for developing world diseases" J. Comb. Chem. 2009, 11, 3-13.
W. L. Scott, J. Alsina, C. O. Audu, E. Babaev, L. Cook, J. L. Dage, L. A. Goodwin, J. G. Martynow, D. Matosiuk, M. Royo, J. G. Smith, A. T. Strong, K. Wickizer, E. M. Woerly, Z. Zhou and M. J. O'Donnell "Distributed Drug Discovery, part 2: Global rehearsal of alkylating agents for the synthesis of resin-bound unnatural amino acids and virtual D3 catalog construction" J. Comb. Chem. 2009, 11, 14-33.
W. L. Scott, C. O. Audu, J. L. Dage, L. A. Goodwin, J. G. Martynow, L. K. Platt, J. G. Smith, A. T. Strong, K. Wickizer, E. M. Woerly and M. J. O'Donnell "Distributed Drug Discovery, part 3: Using D3 methodology to synthesize analogs of an anti-melanoma compound" J. Comb. Chem. 2009, 11, 34-43.
W. L. Scott, J. G. Martynow, J. C. Huffman and M. J. O'Donnell "The solid-phase synthesis of multiple classes of peptidomimetics from versatile resin-bound aldehyde intermediates" J. Am. Chem. Soc.2007, 129, 7077-7088.
P. V. Ramachandran, S. Madhi, L. Bland-Berry, M. V. R. Reddy and M. J. O'Donnell "Catalytic enantioselective synthesis of glutamic acid derivatives via tandem conjugate addition-elimination of activated allylic acetates under chiral PTC conditions" J. Am. Chem. Soc. 2005, 127, 13450-13451.
M. J. O'Donnell "The enantioselective synthesis of a-amino acids by phase-transfer catalysis with achiral Schiff base esters" Acc. Chem. Res. 2004, 37, 506-517.
M. J. O'Donnell, J. T. Cooper and M. M. Mader "Acyclic stereoselective boron alkylation reactions for the asymmetric synthesis of v-substituted a-amino acid derivatives" J. Am. Chem. Soc. 2003, 125, 2370-2371.
M. J. O'Donnell, M. D. Drew, J. T. Cooper, F. Delgado and C. Zhou "The enantioselective synthesis of a-amino acid derivatives via organoboranes" J. Am. Chem. Soc. 2002, 124, 9348-9349.
M. J. O'Donnell and F. Delgado "Enantiomeric enrichment of a-amino acid derivatives: Recrystallization of N-Fmoc a-amino acid t-butyl esters" Tetrahedron 2001, 57, 6641-6650.
M. J. O'Donnell, F. Delgado, E. Dominguez, J. de Blas and W. L. Scott "Enantioselective solution- and solid-phase synthesis of glutamic acid derivatives via Michael addition reactions" Tetrahedron: Asymmetry 2001, 12, 821-828.
M. J. O'Donnell "The preparation of optically active a-amino acids from the benzophenone imines of glycine derivatives" Aldrichimica Acta 2001, 34, 3-15.
M. J. O'Donnell "Asymmetric phase-transfer reactions" in: Catalytic Asymmetric Synthesis, Second Edition, I. Ojima, Ed., Wiley-VCH: New York, 2000, Chap. 10, pp 727-755.
M. J. O'Donnell, F. Delgado and R. S. Pottorf "Enantioselective solid-phase synthesis of a-amino acid Derivatives" Tetrahedron 1999, 55, 6347-6362.
M. J. O'Donnell, F. Delgado, C. Hostettler and R. Schwesinger "An efficient homogeneous catalytic enantioselective synthesis of a-amino acid derivatives" Tetrahedron Lett. 1998, 39, 8775-8778.
M. J. O'Donnell, N. Chen, C. Zhou, A. Murray, C. P. Kubiak, F. Yang and G. G. Stanley "Efficient catalytic enantioselective reaction of a glycine cation equivalent with malonate anions via palladium catalysis" J. Org. Chem. 1997, 62, 3962-3975.
M. J. O'Donnell, C. Zhou and W. L. Scott "Solid-phase Unnatural Peptide Synthesis (UPS)" J. Am. Chem. Soc. 1996, 118, 6070-6071.
M. J. O'Donnell, S. Wu and J. C. Huffman "A new active catalyst species for enantioselective alkylation by phase-transfer catalysis" Tetrahedron 1994, 50, 4507-4518.
M. J. O'Donnell, T. P. Burkholder, V. V. Khau, R. W. Roeske and Z. Tian "Selective alkylation of protected peptide derivatives by phase-transfer catalysis" Pol. J. Chem. 1994, 68, 2477-2488.
M. J. O'Donnell, W. D. Bennett and S. Wu "The stereoselective synthesis of xx a-amino acids by phase-transfer catalysis" J. Am. Chem. Soc. 1989, 111, 2353-2355.
M. J. O'Donnell, W. D. Bennett, W. A. Bruder, W. N. Jacobsen, K. Knuth, B. LeClef, R. L. Polt, F. G. Bordwell, S. R. Mrozack and T. R. Cripe "Acidities of glycine Schiff bases and alkylation of their conjugate bases" J. Am. Chem. Soc. 1988, 110, 8520-8525.
M. J. O'Donnell and R. L. Polt "A mild and efficient route to Schiff base derivatives of amino acids" J. Org. Chem. 1982, 47, 2663-2666.
M. J. O'Donnell and T. M. Eckrich "The synthesis of amino acid derivatives by catalytic phase-transfer alkylations" Tetrahedron Lett. 1978, 4625-4649.
Honors, Awards and Grants
- Plenary Lecturer, Wageningen Symposium on Diversity in Organic Chemistry, Netherlands, 2002
- Closing Plenary Lecture, European Peptide Symposium, France, 2000
- Election of FACET (Faculty Colloquium on Excellence in Teaching), 1998
- President's Award for Distinguished Teaching, 1996
- Chancellor's Award for Excellence in Teaching, 1995
- NCU Fellowship for Research in Japan, 1992
- Purdue School of Science Research Award, 1983
- Loren T. Jones Award, 1981