Research programs in our group aim at the understanding of the mechanism of action of small organic molecules that elicit significant biological responses upon their interactions with biological macromolecules. These organic molecules include active forms of carcinogenic polycyclic aromatic hydrocarbons (PAHs), DNA-cleaving natural products, and glycoconjugate molecules. Chemical synthesis of these compounds, stable isotope-labeled derivatives, and their analogs/inhibitors is an integral part of our overall studies of these biologically intriguing organic molecules. Within each class of compounds, an emphasis is placed on the general applicability, efficiency, and stereo- and regioselectivity of the method to be developed.
The specific projects we are currently involved in include: 1) synthesis of active metabolites of carcinogenic PAHs in optically active form; synthesis of oligonucleotides specifically adducted by these active PAH metabolites and their conformational studies with the use of 2D-NMR techniques; 2) use of the intramolecular cyclization reactions of RZCHR ¥ radicals (Z = O, Si, S, N) in synthesis of biologically important natural products such as the b-lactone lipstatin and the potent immunosuppressant ISP-I and the alkaloid (+)-isonitramine; 3) synthesis of natural 1,2-dithiin (1,2-dithia-3,5-cyclohe-xadiene) and their biological roles including the study on the mode of action on how certain 1,2-dithiin-containing natural products cleave DNA; and 4) synthesis of oligo-saccharides and drug-glycoconjugates (these drugs include antitumor agents such as camptothecin, taxol, and etoposide) for targeted drug delivery.
Chervin, S. M.; Lowe, J. B.; Koreeda, M. "Synthesis and Biological Evaluation of a New Sialyl Lewis X Mimetic derived from Lactose" J. Org. Chem. 2002, 67, 5654-5662.
Houston, T. A.; Chervin, S. M.; Koreeda, M. "Iodine-catalyzed Ferrier N- and C-Glycosylation Reactions" ITE Lett. 2002, 3, 23-25.
Zhang, L.; Koreeda, M. “The Total Synthesis of (+)-Acanthodoral by the Use of a Pd-Catalyzed Metal-ene Reaction and a non-Reductive 5-exo-Acyl Radical Cyclization” Org. Lett. 2004, 6, 537.
Holtsclaw, J.; Koreeda, M. “A Ring-Rearrangement Metathesis Approach toward the Synthesis of Cyclopenta- and Cyclohexa[c]indene Systems” Org. Lett. 2004, 6, 3719.
Zhang, L.; Koreeda, M. “Radical Deoxygenation of Hydroxyl Groups via Phosphites” J. Am. Chem. Soc. 2004, 126, 13190.
Fantegrossi, W. E.; Kugle, K. M.; Valdes, L. J., III; Koreeda, M.; Woods, J. H. “Kappa-Opioid Receptor-mediated Effects of the Plant-derived Hallucinogen, Salvinorin A, on Inverted Screen Performance in the Mouse” Behavioural Pharmacol. 2005, 16, 627.