A. K. Pathak et al. / Tetrahedron Letters 42 (2001) 979–982
981
4. Brennan, P. J.; Nikaido, H. Ann. Rev. Biochem. 1995, 64,
29–61.
dd, J=1.3, 3.1 Hz, H-2), 4.05–3.99 (2H, m, H-3, H-4),
3.89 (1H, m, OCH2), 3.83 (1H, ddd, J=2.3, 4.6, 11.9 Hz,
H-5a), 3.66 (1H, ddd, J=3.4, 7.4, 11.9 Hz, H-5b), 3.57
(1H, m, OCH2), 3.45 (1H, m, CH2), 3.34 (1H, m, CH2),
0.90, 0.89, 0.88, 0.11, 0.09, 0.08 (CH3). 13C NMR
(CDCl3): l 108.54 (C-1), 84.49 (C-4), 83.72 (C-2), 78.23
(C-3), 66.30 (OCH2), 61.63 (C-5), 50.69 (CH2), 25.71,
25.62 (CH3), 17.81, 17.75 (C), −4.42, −4.76, −4.80, −4.98
(CH3). Compound 9: FABMS (LiCl): 898.5 [M+Li]+.
C45H61N3O12Si2·1.7H2O (found: C, 58.45; H, 6.66; N,
4.57; requires: C, 58.57; H, 6.85; N, 4.55). 1H NMR
(CDCl3): l 8.09–7.98, 7.62–7.24 (m, aromatic), 5.59 (1H,
d, J=1.1 Hz, H-2%), 5.56 (1H, d, J=4.8 Hz, H-3%), 5.38
(1H, s, H-1%), 4.84 (1H, dd, J=3.2, 11.8 Hz, H-5%a), 4.83
(1H, d, J=1.4 Hz, H-1), 4.69 (1H, dd, J=4.7, 11.8 Hz,
H-5b% ), 4.62 (1H, ddd, J=3.2, 4.7, 4.7 Hz, H-4%), 4.08 (1H,
m, H-4), 4.06 (1H, dd, J=1.4, 3.7 Hz, H-2), 3.99 (1H, dd,
J=3.7, 6.5 Hz, H-3), 3.89 (1H, dd, J=5.2, 11.2 Hz,
H-5a), 3.82 (1H, m, OCH2), 3.75 (1H, dd, J=3.7, 11.2
Hz, H-5b), 3.51 (1H, m, OCH2), 3.39 (1H, m, CH2), 3.26
(1H, m, CH2), 0.89, 0.87, 0.10, 0.09, 0.08, 0.07 (CH3). 13C
NMR (CDCl3): l 166.18, 165.79, 165.27 (CꢀO), 133.48,
133.44, 133.00, 129.94, 129.85, 129.74, 129.14, 129.10,
128.49, 128.44, 128.27 (aromatic), 108.50 (C-1), 105.95
(C-1%), 84.12 (C-4), 82.09 (C-2, C-2%), 81.25 (C-4%), 79.07
(C-3), 78.05 (C-3%), 66.55 (C-5), 66.36 (OCH2), 63.74
(C-5%), 50.75 (CH2), 25.82, 25.69 (CH3), 17.87, 17.81
(C), −4.27, −4.64, −4.67, −4.90 (CH3). Compound 10:
FABMS (LiCl): 872.7 [M+Li]+. C45H63NO12Si2 (found:
C, 62.14; H, 7.03; N, 1.52; requires: C, 62.40; H, 7.33; N,
1.62). 1H NMR (CDCl3): l 8.09–7.98, 7.71–7.39 (m,
aromatic), 5.58 (1H, s, H-2%), 5.57 (1H, d, J=7.0 Hz,
H-3%), 5.37 (1H, s, H-1%), 4.84 (1H, dd, J=3.1, 11.8 Hz,
H-5a%), 4.83 (1H, d, J=1.5 Hz, H-1), 4.69 (1H, dd, J=4.7,
11.8 Hz, H-5b% ), 4.62 (1H, ddd, J=3.1, 4.7, 7.0 Hz, H-4%),
4.07 (1H, m, H-4), 4.04 (1H, dd, J=1.5, 3.4 Hz, H-2),
3.99 (1H, dd, J=3.4, 5.8 Hz, H-3), 3.89 (1H, dd, J=5.4,
11.0 Hz, H-5a), 3.72 (1H, dd, J=4.3, 11.0 Hz, H-5b), 3.68
(1H, m, OCH2), 3.40 (1H, m, OCH2), 2.82 (2H, m, CH2),
1.95 (2H, br s, NH2), 0.88, 0.87, 0.10, 0.09, 0.08, 0.07
(CH3). 13C NMR (CDCl3): l 166.20, 165.81, 165.30
(CꢀO), 133.49, 133.45, 133.00, 132.14, 132.02, 131.93,
131.90, 129.14, 129.08, 128.56, 128.40 (aromatic), 108.27
(C-1), 105.92 (C-1%), 83.84 (C-4), 82.41 (C-2), 82.12 (C-2%),
81.18 (C-4%), 79.18 (C-3), 78.02 (C-3%), 69.53 (OCH2),
66.85 (C-5), 63.73 (C-5%), 41.96 (CH2), 25.80, 25.70 (CH3),
17.88, 17.82 (C), −4.33, −4.54, −4.66, −4.78 (CH3).
Compound 11: FABMS (LiCl): 1104.7 [M+Li]+.
C57H74N2O14SSi2·2H2O (found: C, 60.01; H, 6.80; N,
2.29; requires: C, 60.29; H, 6.92; N, 2.47). 1H NMR
(CDCl3): l 8.51 (1H, d, J=8.6 Hz, aromatic), 8.30 (1H,
d, J=8.7 Hz, aromatic), 8.22 (1H, dd, J=1.2, 7.3 Hz,
aromatic), 8.06–7.96, 7.60–7.24 (m, aromatic), 7.14 (1H,
d, J=7.6 Hz, aromatic), 5.57 (1H, s, H-2%), 5.56 (1H, d,
J=4.0 Hz, H-3%), 5.32 (1H, s, H-1%), 5.30 (1H, m, NH),
4.83 (1H, dd, J=3.1, 11.6 Hz, H-5%a), 4.69 (1H, d, J=1.8
Hz, H-1), 4.68 (1H, dd, J=4.8, 11.6 Hz, H-5%b), 4.62 (1H,
ddd, J=3.1, 4.0, 4.8 Hz, H-4%), 3.98 (2H, m, H-3, H-4),
4.04 (1H, dd, J=1.8, 3.3 Hz, H-2), 3.84 (1H, dd, J=4.6,
10.9 Hz, H-5a), 3.61 (1H, dd, J=3.5, 10.9 Hz, H-5b), 3.56
(1H, m, OCH2), 3.40 (1H, m, OCH2), 3.05 (2H, m, CH2),
2.86 (2H, s, 2×N-CH3), 0.86, 0.85, 0.08, 0.07, 0.06, 0.05
(CH3). 13C NMR (CDCl3): l 166.14, 165.78, 165.26
5. (a) Young, D. B. Nature 1998, 393, 515–516; (b) Cole, S.
T.; Brosch, R.; Parkhill, J.; Garnier, T.; Churcher, C.;
Harris, D.; Gordon, S. V.; Eiglmeier, K.; Gas, S.; Barry,
III, C. E.; Tekaia, F.; Badcock, K.; Basham, D.; Brown,
D.; Chillingworth, T.; Connor, R.; Davies, R.; Devlin,
K.; Feltwell, T.; Gentles, S.; Hamlin, N.; Holroyd, S.;
Hornsby, T.; Jagels, K.; Barrell, B. G. Nature 1998, 393,
537–544; (c) Duncan, K. Novartis Found. Symp. 1998,
217, 228–238.
6. (a) Winder, F. G. In The Biology of the Mycobacteria;
Ratledge, C.; Standford, J., Eds.; Academic: London,
1982; Vol. 1, pp. 417–521; (b) Mikusova, K.; Slayden, R.
A.; Besra, G. S.; Brennan, P. J. Antimicrob. Agents
Chemother. 1995, 39, 2484–2489.
7. (a) Pathak, A. K.; Besra, G. S.; Crick, D.; Maddry, J. A.;
Morehouse, C. B.; Suling, W. J.; Reynolds, R. C. Bioorg.
Med. Chem. 1999, 7, 2407–2413; (b) Ayers, J. D.;
Lowary, T. L.; Morehouse, C. B.; Besra, G. S. Biorg.
Med. Chem. Lett. 1998, 8, 437–442.
8. (a) Besra, G. S.; Morehouse, C. B.; Rittner, C. M.;
Waechter, C. J.; Brennan, P. J. J. Biol. Chem. 1997, 272,
18460–18466; (b) Xin, Y.; Lee, R. E.; Scherman, M. S.;
Khoo, K.-H.; Brennan, P. J.; Besra, G. S.; McNeil, M.
Biochem. Biophys. Acta 1997, 1335, 231–234.
9. (a) D’Souza, F. W.; Cheshev, P. E.; Ayers, J. D.; Lowary,
T. L. J. Org. Chem. 1998, 63, 9037–9044; (b) D’Souza, F.
D.; Ayers, J. D.; McCarren, P. R.; Lowary, T. L. J. Am.
Chem. Soc. 2000, 122, 1251–1260; (c) D’Souza, F. W.;
Lowary, T. L. Org. Lett. 2000, 2, 1493–1495; (d) Sanchez,
S.; Bamhaoud, T.; Prandi, J. Tetrahedron Lett. 2000, 41,
7447–7452.
10. Pathak, A. K.; El-Kattan, Y. A.; Bansal, N.; Maddry, J.
A.; Reynolds, R. C. Tetrahedron Lett. 1998, 39, 1497–
1500.
11. (a) Maddry, J. A.; Bansal, N.; Bermudez, L. E.; Comber,
R. N.; Orme, I. A.; Suiling, W. J.; Wilson, L. N.;
Reynolds, R. C. Bioorg. Med. Chem. Lett. 1998, 8, 237–
242; (b) Reynolds, R. C.; Bansal, N.; Rose, J.; Friedrich,
J.; Suiling, W. J.; Maddry, J. A. Carbohydr. Res. 1999,
317, 164–179.
12. (a) Lee, R. E.; Mikusova, K.; Brennan, P. J.; Besra, G. S.
J. Am. Chem. Soc. 1995, 117, 11829–11832; (b) Lee, R.
E.; Brennan, P. J.; Besra, G. S. Glycobiology 1997, 7,
1121–1128; (c) Lee, R. E.; Brennan, P. J.; Besra, G. S.
Bioorg. Med. Chem. Lett. 1998, 8, 951–954.
13. Bergmann, F.; Pfleiderer, W. Helv. Chim. Acta 1994, 77,
203–215 and 988–998.
14. Nasir, M. S.; Jolley, M. E. Comb. Chem. High Through-
put Screen. 1999, 2, 177–190.
15. (a) Guthrie, R. D.; Smith, S. C. Chem. Ind. (London)
1968, 547–548; (b) Kam, B. L.; Barascut, J.-L.; Imbach,
J.-L. Carbohydr. Res. 1979, 69, 135–142.
16. (a) For preparation of the
D-sugar, see: Pathak, A. K.;
Pathak, V.; Khare, N. K.; Maddry, J. A.; Reynolds, R.
C. Carbohydr. Lett., submitted for publication; (b) For
preparation of the L-sugar, see: Du, Y.; Pan, Q.; Kong,
F. Carbohydr. Res. 2000, 329, 17–24.
17. Analytical data of selected targets. Compound 7: FABMS
(LiCl): 454.2 [M+Li]+. C19H41N3O5Si2 (found: C, 50.92;
1
H, 9.00; N, 9.58; requires: C, 50.97; H, 9.23; N, 9.39). H
NMR (CDCl3): l 4.85 (1H, d, J=1.3 Hz, H-1), 4.07 (1H,