12
L.Q. Fu et al. / Chinese Chemical Letters 23 (2012) 9–12
In conclusion, a series of pleuromutilin derivatives with novel C(14) side chain were synthesized and evaluated.
The results of antibacterial acticities indicated that most of the pleuromutilin derivatives retained appreciable
antibacterial activities and the length of the linker played an important role. In particular, the compound 10d exhibited
the most potent inhibitory compared with linezoid, which emerged as potential molecule for further investigation.
Acknowledgments
We are grateful to National Science and Technology Major Project for the support of this research. The project
described was supported by Key New Drug Creation and Manufacturing Program, China (No: 2009ZX09301-001).
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[20] Selected data of title compounds: 10a: White solid, yield 59%, mp: 145–146 8C; 1H NMR (300 MHz, CDCl3): d 9.02 (d, 1H, J = 2.0 Hz), 8.50
(dd, 1H, J = 3.1 Hz, 1.5 Hz), 8.31 (d, 1H, J = 8.0 Hz), 7.85 (s, 1H), 7.40–7.55 (3m, H), 7.06 (d, 1H, J = 8.1 Hz), 6.87 (m, 1H), 6.58 (dd, 1H,
J = 17.3, 11.1 Hz), 5.90 (d, 1H, J = 8.8 Hz), 5.39 (d, 1H, J = 11.0 Hz), 5.22 (d, 1H, J = 17.3 Hz), 4.62 (s, 2H), 4.50 (m, 2H), 4.41 (m, 2H), 3.40
(br, 1H), 2.38 (t, 1H, J = 6.6 Hz), 2.10–2.30 (m, 4H), 1.10–1.80 (m, 8H), 1.28 (s, 3H), 1.19 (s, 3H), 0.92 (d, 3H, J = 6.7 Hz), 0.75 (d, 3H,
J = 6.6 Hz); MS (ESI) m/z (689.1 [M+Na]+); Anal. Calcd. for C39H46N4O6: C, 70.25; H, 6.95; N, 8.40. Found: C, 70.22; H, 7.00; N, 8.37. 10d:
White solid, yield 63%, mp: 166 8C; 1H NMR (300 MHz, CDCl3): d 8.58 (s, 1H), 8.46 (d, 1H, J = 4.5 Hz), 8.20 (d, 1H, J = 8.1 Hz), 7.46 (d, 1H,
J = 6.7 Hz), 7.30–7.42 (m, 2H), 6.95 (d, 1H, J = 7.6 Hz), 6.60 (dd, 1H, J = 17.3, 11.1 Hz), 5.92 (d, 1H, J = 8.8 Hz), 5.40 (d, 1H, J = 11.3 Hz),
5.21 (d, 1H, J = 17.5 Hz), 4.82 (m, 2H), 4.60 (s, 2H), 4.50 (m, 2H), 3.40 (br, 1H), 2.38 (t, 1H, J = 6.6 Hz), 2.10–2.30 (m, 4H), 1.10–1.80 (m,
8H), 1.28 (s, 3H), 1.20 (s, 3H), 0.91 (d, 3H, J = 7.1 Hz), 0.76 (d, 3H, J = 6.2 Hz); MS (ESI) m/z (663.1 [M+Na]+); Anal. Calcd. for C37H44N4O6:
C, 69.35; H, 6.92; N, 8.74. Found: C, 69.28; H, 7.11; N, 8.78.