The Synthesis of L-Aminosugar and the Studies of L-Pyranoses on the Ring III of Pyranmycins Jinhua Wang, † Jie Li, † David Tuttle, † Jon Y. Takemoto, ‡ and Cheng-Wei Tom Chang* ,† Department of Chemistry and Biochemistry and Department of Biology, Utah State UniVersity, 0300 Old Main Hill, Logan, Utah 84322-0300 chang@cc.usu.edu Received July 23, 2002 ABSTRACT The synthesis of a novel class of aminoglycoside, pyranmycin, and a convenient method for the preparation of 6-amino-L-idopyranosides were reported. One of the members in the reported pyranmycin families, TC010, has prominent activity against Escherichia coli, Staphylococcus aureus, and Bacillus megaterium. We also discovered that the 4 C 1 chair conformation on ring III of pyranmycin is essential for the antibacterial activity. Neomycin belongs to a group of aminoglycoside antibiotics containing a 4,5-disubstituted 2-deoxystreptamine core and has been used against both gram-positive and gram-negative bacteria for more than fifty years. 1,2 The neomycin class of antibiotics (Figure 1) exert its antibacterial activity by binding selectively to the A-site 16S ribosomal RNA of bacteria, and thereby inhibit the protein synthesis of these microorganisms. Although neomycin is still widely used for the treatment of serious infections, its usefulness is significantly hampered by the rapid emergence of drug resistance 3,4 and its relatively high cytotoxicity. 1 Many neomycin analogues containing a ring III furanose, aiming to increase the antibacterial activity, compensate resistance from aminoglycoside-modifying enzymes, and reduce the cytotoxicity, have been reported. 5-11 However, † Department of Chemistry and Biochemistry. ‡ Department of Biology. (1) Hooper, I. R. Aminoglycoside Antibiotics; Springer-Verlag: New York, 1982. (2) Haddad, J.; Kotra, L. P.; Mobashery, S. In Glycochemistry Principles, Synthesis, and Applications; Wang, P. G., Bertozzi, C. R., Eds.; Marcel Dekker: New York, 2001; pp 307. (3) Cohen, M. L. Science 2002, 257, 1050-1055. (4) Neu, H. C. Science 2002, 257, 1064-1072. (5) Alper, P. B.; Hendrix, M.; Sears, P.; Wong, C.-H. J. Am. Chem. Soc. 1998, 120, 1965-1978. (6) Greenberg, W. A.; Priestley, E. S.; Sears, P. S.; Alper, P. B.; Rosenbohm, C.; Hendrix, M.; Hung, S.-C.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 6527-6541. (7) Yoshikawa, M.; Ikeda, Y.; Takenaka, K. Chem. Lett. 1984, 2097- 2100. (8) Girodeau, J.-M.; Pineau, R.; Masson, M.; Le Goffic, F. J. Antibiot. 1984, 37, 150-158. (9) Woo, P. W. K.; Haskell, T. H. J. Antibiot. 1982, 35, 692-702. (10) Kumar, V.; Jones, G. S., Jr.; Blacksberg, I.; Remers, W. A. J. Med. Chem. 1980, 23, 42-49. Figure 1. Structures of neomycin class antibiotics. ORGANIC LETTERS 2002 Vol. 4, No. 23 3997-4000 10.1021/ol026588r CCC: $22.00 © 2002 American Chemical Society Published on Web 10/15/2002