Department of Chemistry
Martin E. Kuehne
Synthetic Organic Chemistry
Research-Active Emeritus Professor
|Dr. Kuehne received his Ph. D. from Columbia University in 1955 after working with Gilbert Stork. He held a research position at CIBA Pharmaceutical Co. before coming to Vermont in 1961. He has been an Alfred P. Sloan Research Fellow and served as a member of the Medicinal Chemistry Studies Section of the National Institutes of Health. Dr. Kuehne was the 1986-87 University Scholar in the Physical Sciences.|
Based on our previous total syntheses of alkaloids, we are now synthesizing new structures that are designed to increase potential therapeutic activity and to reveal mechanisms of biological activity in the parent compounds. Three current projects illustrate some of our synthetic targets:
Atropisomerism in vinblastine congeners (with variations of n, m, and ring D') can lead to non-cytotoxic pro-drugs for site-activation cancer chemotherapy.
While not cytotoxic, the pauciflorines, with a unique aspidosperma alkaloid derived skeleton, interfere with functioning of melanoma cells and turn off their key formation of melanin. Structural requirements for this activity are unknown and to be determined.
We have found that 18-methoxycoronaridine (18-MC) is a potentially useful anti-addiction agent in that it inhibits demand for morphine, cocaine, alcohol, and nicotine in respectively conditioned rats. 18-MC lacks the toxicities of related iboga alkaloids and its enantiomers show unusual variations in specific drug inhibitions. Drug receptors and structure/activity parameters are to be found.
Kuehne, M. E.; Bornmann, W. G.; Marko, I.; Quin, Y.; LeBoulluec, K. L.; Frasier, D. A.; Feng, X.; Mulamba, T.; Ensinger, C. L.; Borman, L. S.; Huot, A. E.; Exon, C.; Bizzarro, F. T.; Cheung, J. B.; Bane, S. L. "Syntheses and Biological Evaluation of Vinblastine Congener," Organic and Biomolecular Chemistry, 2003, 1, 2120.
Kuehne, M. E.; He, L.; Jokiel, P. A.; Pace, C. J.; Fleck, M. W.; Maisonneuve, I. M.; Glick, S. D.; Bidlack, J. M. "Synthesis and Biological Evaluation of 18-Methoxycoronaridine Congeners. Potential Antiaddiction Agents," J. Med. Chem. 2003, 46, 2716.
Kuehne, M. E.; Cowen, S. D.; Xu, F.; Borman, L. S. "Syntheses of 5a'-homo-Vinblastine and Congeners Designed to Establish Structural Determinants for Isolation of Atopisomers," J. Org. Chem. 2001, 66, 5303.
Kuehne, M. E.; Qin, Y.; Huot, A. E.; Bane, S. L. "The Syntheses of 16a'-homo-Leurosidine and 16a'-homo-Vinblastine. Generation of Atropisomers," J. Org. Chem. 2001, 66, 5317.
Kuehne, M. E.; Wilson, T. E.; Bandarage, U. K.; Dai, W.; Yu, Q. "Enantioselective Syntheses of Coronaridine and 18-Methoxycoronaridine," Tetrahedron 2001, 57, 2085.
Bandarage, U.; Glick, S.; Kuehne, M. E. "Total Syntheses of Racemic Albifloranine and its Anti-Addictive Congeners, Including 18-Methoxycoronaridine," Tetrahedron 1999, 55, 9405.
Xu, F.; Kuehne, M. E. "Syntheses of Strychnan and Aspidospermatan-Type Alkaloids. 9. Enantioselective Generation of Tetracyclic ABCE Intermediates by a Tandem Condensation, [3,3]-Sigmatropic Rearrangement and Cyclization Sequence," J. Org. Chem. 1997, 62, 7950.
Xu, F.; Kuehne, M. E. "Total Syntheses of Strychnan and Aspidospermatan Alkaloids. 3. The Total Synthesis of (±)-Strychnine," J. Org. Chem. 1993, 58, 7490.
Matson, P.; Bornmann, W.; Kuehne, M. E. "Enantioselective Syntheses of Vinblastine, Leurosidine, Vincovaline and 20'-epi-Vincovaline," J. Org. Chem. 1991, 56, 513.
Last modified March 31 2008 09:36 PM