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Scientific Report 2008


Chemistry




Total Synthesis, New Synthetic Technologies, and Chemical Biology


K.C. Nicolaou, A. Agua, R. Aversa, W. Brenzovich, A. Burtoloso, J. Chen, K. Cole, S. Dalby, R. Denton, D. Edmonds, S. Ellery, A. Estrada, B. Fraga, M. Frederick, M. Freestone, C. Gelin, J. Goodwin-Tindall, M. Hesse, P. Huang, V. Jeso, M. Kar, A. Krasovskiy, A. Lemire, A. Li, H. Li, Y. Lim, T. Lister, N. Mainolfi, U. Majumder, C. Mathison, A. Morgan, A. Nold, A. Ortiz, N. Patil, B. Pratt, R. Reingruber, F. Rivas, A. Sanchez Ruiz, D. Sarlah, D. Shaw, A. Stepan, A. Talbot, Y. Tang, V. Trepanier, G. Tria, T. Umezawa, J. Wang, T. Wu, W. Zhan, H. Zhang

We focus on the total synthesis of natural products, the discovery and development of new synthetic technologies, and chemical biology. Naturally occurring substances are selected as synthetic targets for their novel molecular architectures, important biological properties, and interesting mechanisms of action. The projects are designed to optimize the opportunities for discovery and invention in the areas of chemistry, biology, and medicine. The natural products thiostrepton, azaspiracid-1—azaspiracid-3, abyssomycin C, the bisanthraquinones and the marinomycins exemplify this philosophy. Current projects include studies on the antibiotics nocathiacin I, platensimycin, and platencin; the antitumor agents lomaiviticins A and B and uncialamycin; the anti-HIV agent biyouyanagin A; and the marine biotoxin maitotoxin (Fig. 1).


Fig. 1. Selected target molecules.

In addition, we are developing synthetic technologies and strategies for chemical synthesis and chemical biology studies. Our overall aims are to advance the art and science of chemical synthesis and to develop enabling technologies for biology and medicine while maximizing educational opportunities and training of young men and women in chemistry.

Publications

Nicolaou, K.C., Chen, J.S., Zhang, H., Montero, A. Asymmetric synthesis and biological properties of uncialamycin and 26-epi-unicialamycin. Angew. Chem. Int. Ed. 47:185, 2008.

Nicolaou, K.C., Cole, K.P., Frederick, M.O., Aversa, R.J., Denton, R.M. Chemical synthesis of the GHIJK ring system and further experimental support for the originally assigned structure of maitotoxin. Angew. Chem. Int. Ed. 46:8875, 2007.

Nicolaou, K.C., Dethe, D.H., Chen, D.Y.-K. Total syntheses of amythiamicins A, B and C. Chem. Commun. (Camb.) Issue 23:2632, 2008.

Nicolaou, K.C., Dethe, D.H., Leung, G.Y.C., Zou, B., Chen, D.Y.-K. Total synthesis of thiopeptide antibiotics GE2270A, GE2270T, and GE2270C1. Chem. Asian J. 3:413, 2008.

Nicolaou, K.C., Frederick, M.O., Burtoloso, A.C.B., Denton, R.M., Rivas, F., Cole, K.P., Aversa, R.J., Gibe, R., Umezawa, T., Suzuki, T. Chemical synthesis of the GHIJKLMNO ring system of maitotoxin. J. Am. Chem. Soc. 130:7466, 2008.

Nicolaou, K.C., Guduru, R., Sun, Y.-P., Banerji, B., Chen, D.Y.-K. Total synthesis of the originally proposed and revised structures of palmerolide A. Angew. Chem. Int. Ed. 46:5896, 2007.

Nicolaou, K.C., Krasovskiy, A., Trépanier, V.É., Chen, D.Y.-K. An expedient strategy for the synthesis of tryptamines and other heterocycles. Angew. Chem. Int. Ed. 47:4217, 2008.

Nicolaou, K.C., Li, H., Nold, A.L., Pappo, D., Lenzen, A. Total synthesis of kinamycins C, F, and J. J. Am. Chem. Soc. 129:10356, 2007.

Nicolaou, K.C., Lister, T., Denton, R.M., Gelin, C.F. Cascade reactions involving formal [2+2] thermal cycloadditions: total synthesis of artochamins F, H, I, and J. Angew. Chem. Int. Ed. 46:7501, 2007.

Nicolaou, K.C., Lister, T., Denton, R.M., Gelin, C.F. Total synthesis of artochamins F, H, I, and J through cascade reactions. Tetrahedron 64:4736, 2008.

Nicolaou, K.C., Majumder, U., Philippe Roche, S., Chen, D.Y.-K. Construction of the "left-domain" of haplophytine. Angew. Chem. Int. Ed. 46:4715, 2007.

Nicolaou, K.C., Ortiz, A., Denton, R.M. Metathesis reactions in the synthesis of complex molecules. Chem. Today 25:70, 2007.

Nicolaou, K.C., Pappo, D., Tsang, K.Y., Gibe, R., Chen, D.Y.-K. A chiral pool based synthesis of platensimycin. Angew. Chem. Int. Ed. 47:944, 2008.

Nicolaou, K.C., Sun, Y.-P., Guduru, R., Banerji, B., Chen, D.Y.-K. Total synthesis of the originally proposed and revised structures of palmerolide A and isomers thereof. J. Am. Chem. Soc. 130:3633, 2008.

Nicolaou, K.C., Tang, Y., Wang, J., Stepan, A.F., Li, A., Montero, A. Total synthesis and antibacterial properties of carbaplatensimycin. J. Am. Chem. Soc. 129:14850, 2007.

Nicolaou, K.C., Tria, G.S., Edmonds, D.J. Total synthesis of platencin. Angew. Chem. Int. Ed. 47:1780, 2008.

Nicolaou, K.C., Wang, J., Tang, Y. Synthesis of the sporolide ring framework through a cascade sequence involving an intramolecular [4+2] cycloaddition reaction of an o-quinone. Angew. Chem. Int. Ed. 47:1432, 2008.

Vale, C., Gómez-Limia, B., Nicolaou, K.C., Frederick, M.O., Vieytes, M.R., Botana, L.M. The c-Jun-N-terminal kinase is involved in the neurotoxic effect of azaspiracid-1. Cell. Physiol. Biochem. 20:957, 2007.

Vilariño, N., Nicolaou, K.C., Frederick, M.O., Vieytes, M.R., Botana, L.M. Irreversible cytoskeletal disarrangement is independent of caspase activation during in vitro azaspiracid toxicity in human neuroblastoma cells. Biochem. Pharmacol. 74:327, 2007.

 

K.C. Nicolaou, Ph.D.
Chairman and Professor



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