个人简介
2013-present Associate Vice President for Research, University of Notre Dame
2008-2013 Associate Dean, College of Science, University of Notre Dame
2004-present Professor, University of Notre Dame
2001-2004 Associate Professor, University of Notre Dame
1995-2001 Assistant Professor, University of Notre Dame
1992-1995 Merck Postdoctoral Associate, Stanford University
1992 Ph.D. in Chemistry, Rensselaer Polytechnic Institute
1987 B.S. in Chemistry, State University of New York, Oswego
Selected Awards
2009 Elected Fellow, American Association for the Advancement of Science
2007 Rev. Edmund P. Joyce Award for Excellence in Undergraduate Teaching
2007 Silveira Distinguished Lecturer, SUNY, Oswego
2002 Kaneb Teaching Award
2000 Eli Lilly Grantee Award
1998 NSF Early Career Award
研究领域
Organic Chemistry
Our group is interested in the exploring the potential of polyketide natural products as chemotherapeutic agents particularly directed against cancer. Towards this end our group's expertise includes synthetic chemistry, molecular modeling, and molecular biology/biochemistry. In recent years the we have completed the total synthesis of the complex natural products, epothilones A, B, C and D, myriaporones 1, 3 and 4, peloruside A, neopeltolide, tolypothrix polyethers, and gephyronic acid.
Our analogue design strategy is focused towards the determination of the structural and conformational constraints of binding. Our group has demonstrated that the information gained from what we have termed conformation-activity relationships complements classic SAR with the goal of providing a detailed pharmacophore model and assist in the design of future chemotherapeutic agents. In addition to our successful total syntheses and medicinal chemistry efforts, our group has already contributed significantly to the field of organic synthesis through the development of a number of new synthetic methodologies that solved key problems in our targeted efforts.
Another unique aspect of our analogue design strategy is the exploitation of biosynthetic enzymes called polyketide synthases. We are actively pursuing the isolation and characterization of polyketide synthase gene clusters responsible for the production of biologically active natural products. We have demonstrated the semi-synthetic production of epothilone natural products and analogues through the use of genetically engineered organisms thus alleviating any concerns about the high cost of total synthesis of compounds of this complexity.
近期论文
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Stefan, E.; Taylor, R. E. "1,5-Hydride Transfer Protocol for the Synthesis of beta-Branched Polyketide Structural Units" Tetrahedron Lett. 2015, 56, published online January 10, 2015.
Stevens, D. C.; Young, J.; Carmichael, R.; Tan, J.; R. E. "Draft Genome Sequence of Gephyronic Acid Producer Cystobacter violaceus Strain Cb vi76″ Genome A 2014, 2, e01299-14.
Young, J.; Stevens, D. C; Carmichael, R.; Tan, J.; Rachid, S.; Boddy, C. N.; Müller, R.; Taylor, R. E. "Elucidation of Gephyronic Acid Biosynthetic Pathway Revealed Unexpected SAM Dependent Methylations" J. Nat. Prod. 2013, 76, 2269-2276.
Larsen, E.; Wilson, M. R.; Zajicek, J.; Taylor, R. E. "Conformational Preferences of Zampanolide and Dactylolide" Org. Lett. 2013, 15, 5246-5249.
Stefan, E.; Nalin, A. P.; Taylor, R. E. "Concise Enantioselective Synthesis of Diospongins A and B" Tetrahedron 2013, 69, 7706-7712.
Wilson, M. R.; Taylor, R. E. " Strained Alkenes in Natural Product Synthesis" Angew. Chem. Int. Ed. 2013, 52, 4078-4087.
Muthukumar Y.; Roy, M.; Raja, A.; Taylor, R. E.; Sasse, F. "The Marine Polyketide Myriaporone 3/4 Stalls Translation by Targeting the Elongation Phase" ChemBioChem 2013, 14, 260-264.
Stefan, E.; Taylor, R. E. "Stereoselective Synthesis of the C9–C19 Fragment of Lyngbyaloside B and C via Ether Transfer" Org. Lett. 2012, 14, 3490-3493.
Wilson, M. R.; Taylor, R. E. "Toward an Enantioselective Synthesis of (−)-Zampanolide: Preparation of the C9–C20 Region" Org. Lett. 2012, 14, 3408-3411.
Zhao, Z.; Taylor, R. E. "Rapid Access to Conformational Analogues of Peloruside A" Org. Lett. 2012, 14, 669-671.
Anderl, T.; Nicolas, L.; Münkemer, J.; Muthukumar, Y.; Baro, A.; Frey, W.; Sasse, F.; Taylor, R. E. Laschat, S.; "Synthesis and Biological Evaluation of Gephyronic Acid Derivatives – Initial Steps Toward Identification of the Biological Target of Polyketide Inhibitors of Eukaryotic Protein Synthesis" Eur. J. Org. Chem. 2011, , 3387-3396.
Begaye, A.; Trostel, S.; Zhao, Z.; Taylor, R. E.; Schriemer, D. C.; Sackett, D. L. "Mutations in the beta-tubulin binding site for peloruside A confer riesistance by targeting a cleft significant in sidechain binding" Cell Cycle 2011, 10:19, 3387-3396.
Anderl, T.; Nicolas, L; Mükemer, J.; Baro, A.; Sasse, F.; Steinmetz, H.; Jansen, R.; Höfle, G.; Taylor, R. E.; Laschat, S. "Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid" Angew. Chem. Int. Ed. 2011, 50, 942-945.
Nicolas, L; Anderl, T.; Sasse, F.; Steinmetz, H.; Jansen, R.; Höfle, G.; Laschat, S.; Taylor, R. E. "Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part I): Structural Revision and Stereochemical Assignment of Gephyronic Acid" Angew. Chem. Int. Ed. 2011, 50, 938-941.
Anderl, T.; Nicolas, L; Mükemer, J.; Baro, A.; Sasse, F.; Steinmetz, H.; Jansen, R.; Höfle, G.; Taylor, R. E.; Laschat, S. "Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid" Angew. Chem. Int. Ed. 2011, 50, 942-945.
Liu, K.; Arico, J. W.; Taylor, R. E. "Application of Stereoselective Ether Transfer to the Synthesis of Isotactic Polyethers" J. Org. Chem. 2010, 75, 3953-3957.
Frein, J.D.; Taylor, R. E.; Sackett, D.L. "New Sources of Chemical Diversity Inspired by Biosynthesis: Rational Design of a Potent Epothilone Analogue" Org. Lett. 2009, 11, 3186-3189.
Daly, E., Taylor, R. E ""Entropy and Enthalpy in the Activity of Tubulin-based Antimitotic Agents" Curr. Chem. Biol. 2009, 3, 367-379.
Taylor, R. E.; Diene, C. R.; Daly, E. M. "46.11 Synthesis of 1,3-Dienes by Isomerization of Unconjugated Dienes, Allenes, and Alkynes" in Houben-Weyl Science of Synthesis; V. H. Rawal and S. A. Kozmin, Eds.; G. Thieme Verlag, Stuttgart, 2009, Vol. 46, 549-584.
Kartika, R.; Gruffi, T. R.; Taylor, R. E. "Efficient Total Synthesis of Neopeltolide Macrolactone Highlighted by Ether Transfer" Org. Lett. 2008, 10, 5047-5050.