4051
9. Deacetylation of 9 with sodium methoxide in methanol gave the pseudo-trisaccharide 10 in 56% yield
over two steps. Reduction of azido groups in 10 by Me3P/THF/H2O/NaOH yielded compound 2 in 62%
yield.
Compound 3 was synthesized from the coupling reaction of 4,6-di-O-acetyl-1,3-diazido-2-
deoxystreptamine (12) and 1,2,5,30,40-penta-O-acetyl-20,60-diazidoneobiosamine (14). Treatment
of 1,3-diazido-2-deoxy-streptamine (11)11 with 2 equiv. acetic anhydride in pyridine at −10°C gave
the glycosyl acceptor 12 in 25% yield. NMR and mass spectral data of 12 confirmed that two acetyl
groups were located at the 4 and 6 positions. The neobiosamine derivative 14, in which all the functional
groups are protected, was prepared from neobiosamine 13.12 Treatment of 13 with TfN3, followed by
acetylation with acetic anhydride in pyridine, gave the glycosyl donor 14 in 52% yield. Glycosylation
of 12 with 14 in dichloromethane in the presence of TMSOTf gave the pseudo-trisaccharide 15 in 55%
yield. Deacetylation of 15 with sodium methoxide in methanol gave the partially protected derivative
16. Reduction of the azido groups of 16 by the reaction with Me3P/NaOH/THF/H2O gave compound 3
in 73% yield for two steps.
Compounds 2 and 3 will be used as standards to compare RNA binding activities with ribostamycin
(1), neomycin B and paromomycin, and then to determine the relationship between the structures of
aminoglycosides and RNA binding activities.
Aminoglycosides provide several important lessons in the design of compounds that bind to
RNA.13 The synthesis of aminoglycosides reported here provides efficient access to some interesting
aminoglycoside structures, and this work may be useful for synthesizing unnatural aminoglycoside
derivatives.14
References
1. Stage, T. K.; Hertel, K. J.; Uhlenbeck, O. C. RNA 1995, 1, 95–101.
2. Green, M. R. AIDS Res. Rev. 1993, 3, 41–55.
3. von Ahsen, U.; Davies, J.; Schroeder, R. Nature 1991, 353, 368–370.
4. Koeda, T.; Umemura, M.; Yokota, M. Aminoglycoside Antibiotics; Umezawa, H.; Hooper, I. R., Eds.; Springer: New York,
1982; pp. 293–356.
5. von Ahsen, U.; Noller, H. F. Science 1993, 260, 1500–1503.
6. Kumar, V.; Remers, W. A. J. Org. Chem. 1981, 46, 4298–4300.
7. Hanessian, S.; Takamoto, T.; Masse, R.; Patil, G. Can. J. Chem. 1978, 56, 1482–1491.
8. Hanessian, S.; Masse, R.; Ekborg, G. Can. J. Chem. 1978, 56, 1492–1499.
9. Huchenrauch, R.; Keiner, I. Pharm Zentralhalle Dtschi 1967, 106, 665–668.
10. Vasella, A.; Witzig, C.; Chiara, J.-L; Martin-Lomas, M. Helv. Chim. Acta 1991, 74, 2073–2077.
11. Alper, P. B.; Hung, S. C.; Wong, C. H. Tetrahedron Lett. 1996, 37, 6029-6032.
12. Rinehart Jr., K. L. The Neomycins and Related Antibiotics; John Wiley and Sons: New York, 1964; pp. 93–97.
13. Ecker, D. J.; Griffey, R. H. Drug Discovery Today 1999, 4, 420–429.
14. Spectral data for selected compounds. Compound 6: 1H NMR (CDCl3, 400 MHz) δ 5.42 (1H, t, J=9.2), 5.32 (1H, d, J=3.6,
H-10), 4.98 (1H, t, J=9.2), 4.89 (1H, t, J=9.2), 4.31 (1H, dt, J=2.0, 10.4), 4.23 (1H, dd, J=4.4, 12.4), 4.05 (1H, dd, J=2.4,
12.4), 3.61 (1H, t, J=9.2), 3.56 (1H, dd, J=4, 10.4), 3.48 (1H, ddd, J=4.8, 10.0, 12.4), 3.41 (1H, t, J=9.2), 3.30 (1H, ddd,
J=4.8, 10.0, 12.4), 2.33 (1H, dt, J=4.4, 13.2, H-2α), 2.11 (3H, s), 2.03 (3H, s), 2.02 (3H, s), 1.99 (3H, s), 1.59 (1H, q,
J=12.4, H-2β); 13C NMR (CDCl3, 400 MHz) δ 99.1 (C-10), 83.3, 75.2, 74.6, 71.3, 68.5, 68.4, 62.0, 61.8, 58.5, 58.1, 31.9
1
(C-2). Compound 7: H NMR (CDCl3, 400 MHz) δ 5.36 (1H, t, J=9.2), 5.05 (2H, m), 4.96 (1H, t, J=9.2), 4.82 (1H, t,
J=9.3), 4.36 (1H, d, J=10.2), 4.22 (1H, d, J=10.3), 4.04 (1H, d, J=10.3), 3.46 (2H, m), 3.36 (1H, m), 3.24 (1H, dt), 2.26
(1H, m, H-2α), 1.48 (1H, q, J=12.4, H-2β). Compound 9: 1H NMR (CD3OD, 400 MHz) δ 6.01 (1H, d, J=3.9, H-10), 5.46
(1H, t, J=7.6), 5.45 (1H, d, J=4.0, H-100), 5.22 (1H, t, J=3.0), 5.12 (1H, t, J=3.1), 5.02 (1H, t, J=7.8), 4.97 (1H, t, J=7.9),
4.46 (1H, dt), 4.40 (1H, dd), 4.27 (1H, m), 4.20 (2H, m), 3.99 (1H, t, J=7.8), 3.78 (1H, t, J=7.9), 3.65 (2H, m), 2.36 (1H,
m, H-2α), 1.59 (1H, q, J=12.4, H-2β); 13C NMR (CD3OD, 400 MHz) δ 106.7 (C-10), 96.2 (C-100), 81.6, 79.5, 76.2, 75.0,