ORGN 276 |
| Although many natural products contain halogen, those harbouring halogenated amino acids as constituents are much less known. The aeruginosin group of cyanobacterial linear peptides isolated as secondary metabolites from diversely located aquatic origins, are endowed with unique structures and important in vitro activities against serine proteases such as thrombin and trypsin. The structures and absolute configurations of a few members of this family have been reported as a result of total syntheses and X-ray co-crystal complexes with the enzyme thrombin among others. Three total syntheses of Aeruginosin 298A have been published from the Bonjoch, Wipf, and Shibasaki laboratories independently. The total syntheses of Dysinosin A, Oscillarin, and Chlorodysinosin A containing an unprecedented cyclic amidino 3-pyrroline P1 moiety as an arginine mimetic, were reported by our group thereby establishing their definitive structures and absolute configuration. Chlorodysinosin A harbors a novel 2S, 3R-chloroleucine residue found for the first time in a natural product. Efforts toward the total synthesis of chlorodysinosin A and related compounds with a discussion of their activities in the light of X-ray co-crystal structures and molecular modeling will be highlighted. Pertinent literature: Dysinosin A: S. Hanessian, R. Margarita, A. Hall, Johnstone, M. Tremblay, L. Parlanti J. Am. Chem. Soc. 2002, 124, 13342; Oscillarin : S. Hanessian, M. Tremblay, J. F. Petersen J. Am. Chem. Soc. 2004, 126, 6064; Chlorodysinosin A : S. Hanessian, J. R. Del Valle, Y. Xue, N. Blomberg J. Am. Chem. Soc. 2006, 128, 10491. Aeruginosin 298A: N. Valls, M. López-Canet, M. Vallribera, J. Bonjoch J. Am. Chem. Soc. 2000, 122, 11248; P. Wipf, J.-L. Methot Org. Lett. 2000, 2, 4213; T. Ohshima, V. Gnanadesikan, T. Shibuguchi, Y. Fukuta, T. Nemoto, M. Shibasaki J. Am. Chem. Soc. 2003, 125, 11206. |
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Asymmetric Syntheis of α-Amino Acids: Novel Developments and Future Directions
1:00 PM-5:40 PM, Monday, March 26, 2007 McCormick Place Lakeside -- Room E350, Level 3, Oral
Division of Organic Chemistry |