Contact

 

Edward C. Taylor
A. Barton Hepburn Professor of Organic Chemistry, Emeritus; Seni
etaylor@princeton.edu
Frick Laboratory, 127
609-258-3914

Faculty Assistant

Denise D'Auria
denised@princeton.edu
Frick Laboratory, 228
609-258-5202

Research Focus

Taylor’s career has involved pioneering studies in organic synthesis methodology, organometallic chemistry, natural products and medicinal chemistry. Early work included new approaches to the synthesis, inter alia, of purines, quinine, tetrahydrocannabinol, the molybdenum cofactor, biopterin, xanthopterin, urothione and Asperopterin B. Continuing features of his syntheses were exploitations of molecular rearrangements devised to simplify synthetic transformations. Together with a former postdoctoral associate, Alexander McKillop, and using new thallium-based reagents, they discovered some 130 new organic synthetic transformations. He was one of the first to recognize and highlight the remarkable versatility of heterocyclic N-oxides for synthetic transformations.



Taylor’s fascination with heterocyclic chemistry included pteridine chemistry. The pteridine ring system was first identified in a study of the constituents of butterfly wing pigments, and pteridines thus were initially viewed as occupying an esoteric, insignificant corner of natural product chemistry. We now know, however, that two pteridine derivatives, the molybdenum cofactor and folic acid, are critical components of all living cells, and are required for all forms of life. Cofactors derived from folic acid play key roles in a host of diverse metabolic reactions essential for the formation of DNA, RNA, ATP, amino acids and proteins. Taylor’s involvement in heterocyclic and folate chemistry included a search for inhibitors of folate-dependent enzymes, and led in the late 1970s to his discovery that (6R)-5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF) blocked de novo purine biosynthesis, and exhibited unprecedented activity against a variety of solid tumors. To further explore and develop this promising new area, Princeton and Eli Lilly & Co. set up a collaborative research effort to search for further inhibitors of folate-dependent processes.

This effort, that involved synthesis and evaluation of many hundreds of new potential agents, culminated in Taylor’s synthesis of a remarkable new oncolytic agent (N-{4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid) that became known as Alimta™ (pemetrexed disodium), licensed to, developed and marketed by Eli Lilly & Company. Alimta™ exhibits a remarkable breadth of antitumor activity that results from inhibition of three of the major folate-dependent enzymes in cellular metabolism. Alimta™, in combination with cis-platin, was approved by the FDA in 2004 for the treatment of malignant pleural mesothelioma, later in 2004 as a single agent for second-line non-small cell lung cancer (NSCLC), and several years later for first-line and maintenance therapy for NSCLC. It is now in use in more than 100 countries, and is in multiple further clinical trials, both in combination with other oncolytics and as a single agent, for a wide range of other solid tumors. Royalties to Princeton University from Lilly are responsible for the construction of the new chemistry building that opened in 2010.

Research Areas
Catalysis / Synthesis
Selected Recent Publications

Taylor, E. C.; Bhatia, B., "Synthesis and bridgehead reactions of 9-substituted 5,6,7,8,9,10-hexahydro-5,9-methanopyrimido 4,5-b azocin-4(3H)-ones." Heterocycles 2003, 61, 113-+.

Taylor, E. C.; Liu, B., "A new and efficient synthesis of pyrrolo 2,3-d pyrimidine anticancer agents: Alimta (LY231514, MTA), homo-alimta, TNP-351, and some aryl 5-substituted pyrrolo 2,3-d pyrimidines." Journal of Organic Chemistry 2003, 68 (26), 9938-9947.

Taylor, E. C.; Liu, B., "A new route to 7-substituted derivatives of N-{4- 2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo 2,3-d pyrimidin-5-yl)ethyl benzoyl}-L-glutamic acid ALIMTA (LY231514, MTA)." Journal of Organic Chemistry 2001, 66 (11), 3726-3738.

aylor, E. C.; Chaudhuri, R. P.; Watson, S. E., "Potential silicon-containing antifolates." Tetrahedron 1999, 55 (6), 1631-1638.

Taylor, E. C.; Dowling, J. E.; Bhatia, B., "Synthesis of 2,4-diamino-5,6,7,8,9,10-hexahydro-5,9-methanopyrimido 4,5-b azocine." Journal of Organic Chemistry 1999, 64 (2), 441-446.

Taylor, E. C.; Liu, B., "A novel synthetic route to 7-substituted derivatives of the antitumor agent LY231514 (MTA)." Tetrahedron Letters 1999, 40 (29), 5291-5294.

Taylor, E. C.; Liu, B., "A simple and concise synthesis of LY231514 (MTA)." Tetrahedron Letters 1999, 40 (21), 4023-4026.

Taylor, E. C.; Liu, B., "Exploitation of a new route to fused pyrroles: Synthesis of TNP-351, homo-MTA and 5-arylpyrrolo 2,3-d pyrimidines." Tetrahedron Letters 1999, 40 (21), 4027-4030.

Taylor, E. C.; Wang, Y., "Synthesis of 7-methyl derivatives of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), 5,10-dideaza-5,6,7,8-tetrahydrohomofolic acid (HDDATHF), and LY254155." Heterocycles 1998, 48 (8), 1537-1554.

Taylor, E. C.; Zhou, P.; Tice, C. M., "6-trifluoromethanesulfonyloxy-4(3H)-pyrimidinones as versatile intermediates for the synthesis of 6-functionalized 4(3H)-pyrimidinones." Tetrahedron Letters 1997, 38 (25), 4343-4346.

Taylor, E. C.; Zhou, P.; Tice, C. M.; Lidert, Z.; Roemmele, R. C., "Synthesis of 2-(2,6-dichloro-4-pyridyl)-3-propargyl-5-ethyl-6-methyl-4(3H)-pyrimidino ne, a promising new herbicide." Tetrahedron Letters 1997, 38 (25), 4339-4342.

Taylor, E. C.; Dowling, J. E., "Replacement of the 1',4'-phenylene region in 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF) by 4,5,6,7-tetrahydrobenzo c thiophene and 4,5,6,7-tetrahydroisobenzofuran nuclei." Journal of Organic Chemistry 1997, 62 (6), 1599-1603.

Taylor, E. C.; Hu, B. H., "Synthesis of some conformationally-constrained glutamate mimics of (N)under-bar-{5- 2-(2-amino-3,4-dihydro-4-oxo-5,6,7,8-tetrahydropyrido 2 ,3-(d)under-bar pyrimidin-6-yl)ethyl thien-2-ylcarbonyl}-L-glutamic acid (LY254155)." Heterocycles 1997, 45 (2), 241-253.

Taylor, E. C.; Jennings, L. D.; Mao, Z. M.; Hu, B. H.; Jun, J. G.; Zhou, P., "Synthesis of conformationally-constrained glutamate analogues of the antitumor agents DDATHF, LY254155, and LY231514." Journal of Organic Chemistry 1997, 62 (16), 5392-5403.

Taylor, E. C.; Hu, B. H., "A Fischer-Indole approach to pyrrolo 2,3-d pyrimidines." Heterocycles 1996, 43 (2), 323-338.

Sakurai, A.; Hashimoto, Y.; Kuboyama, N.; "Takahashi, Y.; Okumura, Y., Studies on urothion. Synthesis of (R)-dephospho form B, a degradation product of the molybdenum cofactor." Heterocyclic Communications 1996, 2 (4), 383-386.

Taylor, E. C.; Young, W. B., "Pyrrolo 3,2-D pyrimidine folate analogs - inverted analogs of the cytotoxic agent ly231514." Journal of Organic Chemistry 1995, 60 (24), 7947-7952.

Taylor, E. C.; Yoon, C.-M., "Synthesis of 10-(hydroxymethyl)-5,10-dideaza-5,6,7,8-tetrahydrofolic acid, a potent new analogue of DDATHF (Lometrexol)." Journal of Organic Chemistry 1994, 59 (23), 7096-7098.

Taylor, E. C.; Yoon, C., "Synthesis of 10-(hydroxymethyl)-5,10-dideaza-5,6,7,8-tetrahydrohomofolic acid, a potent new analog of DDATHF (lometrexol)." Journal of Organic Chemistry 1994, 59 (23), 7096-7098.

Taylor, E. C.; Yoon, C.; Hamby, J. M., "Inhibitors of glycinamide ribonucleotide formyltransferase as potential cytotoxic agents - synthesis of 5-deaza-5,6,7,8-tetrahydrohomofolic acid, 5-deaza-5,6,7,8-tetrahydrohomofolic acid, and 10-formyl-5-deaza-5,6,7,8-tetrahydrohomofolic acid." Journal of Organic Chemistry 1994, 59 (23), 7092-7095.

Taylor, E. C.; Young, W. B.; Ward, C. C., "An expeditious synthesis of 2-amino-4(3H)-oxo-5H-pyrrolo 3,2-D pyrimidine (9-deazaguanine)." Tetrahedron Letters 1993, 34 (29), 4595-4598.

Taylor, E. C.; Kuhnt, D.; Shih, C.; Rinzel, S. M.; Grindey, G. B.; Barredo, J.; Jannatipour, M.; Moran, R. G., "A dideazatetrahydrofolate analog lacking a chiral center at C-6, N- 4- 2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo 2,3-D pyrimidn-5-YL)Ethyl Benzoyl-L-glutamic acid, is an inhibitor of thymidylate synthase." Journal of Medicinal Chemistry 1992, 35 (23), 4450-4454.

Taylor, E. C.; Schrader, T. H.; Walensky, L. D., "Synthesis of 10-substituted open-chain analogs of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF, LOMETREXOL)." Tetrahedron 1992, 48 (1), 19-32.

aylor, E. C.; Reiter, L. A., "Studies on the molybdenum cofactor - an unequivocal total synthesis of (+/-)-Urothione." Journal of the American Chemical Society 1989, 111 (1), 285-291.

Bide, A. E.; Henbest, H. B.; Jones, E. R. H.; Peevers, R. W.; Wilkinson, P. A., "Studies in the sterol group. XLVII. A new route to 7-dehydrocholesterol (provitamin D3) and its derivatives. XLVIII, XLIX, and XL. 7-Substituted cholesterol derivatives and their stereochemistry. I. 7-Halogeno derivatives. II. Esters of the epimeric 7-hydrocholesterols. III. 7-Alkoxycholesterol derivatives." Jour Chem Soc [London] 1948, 1948 ((11)), 1783-1803.