Researchers
Richard E. Taylor, Ph.D.
Professor, Department of Chemistry and Biochemistry
Contact Information
Biography
Professor Taylor obtained his B.S. degree in chemistry in 1987 from the State University of New York, Oswego. He received his Ph.D. degree in 1992 in chemistry from Rensselaer Polytechnic Institute where he developed synthetic methodology for the enantioselective preparation of chiral cyclohexanes and dioxadiaza-crown ethers and used molecular modeling to understand crown ether conformational preferences. Subsequently, as a Merck postdoctoral research associate at Stanford University, he developed a total synthesis of the anticancer agent, taxol. In 1995, Professor Taylor joined the faculty of the University of Notre Dame. Professor Taylor was the recipient of the National Science Foundation Early Career Award, an Eli Lilly Grantee award, and the University of Notre Dame Kaneb Teaching Award. He is a co-author of over 40 papers and has presented over 80 invited lectures.
Research Interests
Professor Taylor's group has investigated a number of complex polyketide natural products, with unique or unknown modes of action. His expertise in the area of synthesis, conformational analysis and polyketide biosynthesis has placed his lab in a unique position to fully exploit these lead structures potential as therapeutic agents. In the last four years his group has completed the total synthesis of the epothilones A, B, C and D, myriaporones 1, 3 and 4, and most recently, the marine polyketide, peloruside A. In addition, his lab has prepared modified versions of these compounds, analogues, to learn more about the importance of key structural features with unique perspective focused on the determination of the bound conformation. Through their detailed study of several designed epothilones they proposed a bound conformation that was later independently supported by NMR studies of the protein-bound ligand. Moreover, his group identified unique analogues that were patented and licensed to the pharmaceutical industry for further development. Prof. Taylor's group has demonstrated that the information gained from what they 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. Another unique aspect of his analogue design strategy is the exploitation of biosynthetic enzymes called polyketide synthases. Prof. Taylor's group has 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. In addition to their successful total syntheses and medicinal chemistry efforts, his 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. In the past several years, his group has published new approaches to the synthesis of cyclopropane structural units (ambruticin), hydroxypropionate functionality (myriaporones and tedanolide), trisubstituted olefins (apoptolidin and epothilones) and 1,3-diol monoethers (peloruside A).
Publications
Jin M, Taylor RE. The total synthesis of (+)-peloruside A. Org Lett 2005; 7: 1303-1305. link
Fleming KN, Taylor RE. Total synthesis and stereochemical assignment of myriaporones 1, 3, and 4. Angew Chem Int Ed 2004; 43: 1728-1730. link
Suckow MA, Gutierres LS, Risatti CA, Wolter WR, Taylor RE, Pollard M, Navari RM, Castellino FJ, Paoni NF. The anti-ischemia agent ranolazine promotes the development of intestinal tumors in APC(Min/+) mice. Cancer Lett 2004; 209: 165-169. link
Taylor RE, Chen Y, Galvin GM, Pabba P. Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone. Org Biomol Chem 2004; 2: 127-132. link
Yoshimura F, Rivkin A, Gabarda AE, Chou TC, Dong H, Sukenick G, Morel FF, Taylor RE, Danishefsky SJ. Synthesis and conformational analysis of (E)-9,10-dehydro epothilone B: A suggestive link between the chemistry and biology of epothilones. Angew Chem Int Ed 2003; 42: 2518-2521. link
Hines J, Roy M, Cheng H, Agapakis CM, Taylor RE, Crews CM. Myriaporone 3/4 SAR Studies Reveal a Novel Pharmacophore Targeting Eukaryotic Protein Synthesis. Mol. Biosystems 2006, 2, 371-379. [Highlighted on the cover.] link
Liu K, Taylor RE, Kartika R. Electrophile-Induced Ether Transfer: A New Approach to Polyketide Structural Units. Org. Lett. 2006, 8, in press.
