Novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain
Q-L Song et al
579
(m, 1H), 1.55B1.61 (m, 2H), 1.47 (s, 3H), 1.35 (d, J¼6.8 Hz, 3H), 1.22B1.29 Compound 11i
Yield 53.0%. 1H NMR (400MHz, CDCl3): d 8.77 (d, J¼4.8Hz, 1H), 8.35
(d, J¼8.0 Hz, 1H), 7.89 (dt, J¼1.7, 7.8 Hz, 1H), 7.44 (m, 1H), 4.91B4.99 (m,
3H), 4.28 (d, J¼7.3 Hz, 1H), 4.24 (d, J¼8.6Hz, 1H), 3.84 (q, J¼6.7 Hz, 1H),
3.50B3.64 (m, 4H), 3.16B3.20 (m, 1H), 3.05B3.14 (m, 2H), 2.62 (s, 3H),
2.42B2.49 (m, 1H), 2.27 (s, 6H), 1.93B2.00 (m, 3H), 1.82 (dd, J¼14.5, 2.3 Hz,
1H), 1.55B1.69 (m, 5H), 1.46 (s, 3H), 1.24B1.38 (m, 15H), 1.16 (d, J¼7.0 Hz,
3H), 1.00 (d, J¼6.9 Hz, 3H), 0.85 (t, J¼7.3 Hz, 3H). 13C NMR (100MHz,
CDCl3): d 216.0, 203.7, 169.5, 157.1, 151.6, 149.6, 145.0, 137.3, 125.1, 124.5,
103.9, 82.1, 79.5, 78.1, 77.2, 70.3, 69.6, 65.9, 60.5, 51.2, 49.7, 49.6, 47.5, 44.9,
43.3, 40.2, 39.5, 39.0, 29.6, 28.2, 26.5, 23.8, 22.3, 21.2, 19.7, 18.3, 15.7, 14.6,
14.3, 13.9, 10.4. MS (ESI) [M+H]+ m/z 829.1. HRMS (ESI, m/z) calcd for
C42H65N7O10 828.4866, found 828.4859.
(m, 12H), 1.14 (d, J¼6.9 Hz, 3H), 1.01 (d, J¼6.9 Hz, 3H), 0.87 (t, J¼7.4 Hz,
3H); 13C NMR (100MHz, CDCl3): d 216.0, 203.6, 169.7, 163.1, 157.2, 150.5,
135.0, 120.9, 103.9, 82.4, 79.6, 78.2, 77.3, 70.3, 69.5, 65.9, 60.7, 51.2, 51.1, 49.7,
47.6, 44.8, 41.4, 40.2, 39.5, 38.9, 28.2, 27.1, 22.2, 21.1, 19.6, 18.2, 15.8, 14.5,
14.3, 13.8, 10.4. MS (ESI) [M+H]+ m/z 801.0. HRMS (ESI, m/z) calcd for
C40H61N7O10 800.4553, found 800.4568.
Compound 11e
Yield 60.1%. 1H NMR (400 MHz, CDCl3): d 8.78 (d, J¼4.8 Hz, 1H), 8.35
(d, J¼7.5 Hz, 1H), 7.89 (t, J¼7.8 Hz, 1H), 7.44 (m, 1H), 4.96B5.08 (m, 2H),
4.91 (d, J¼10.5Hz, 1H), 4.29 (d, J¼7.3Hz, 1H), 4.24 (d, J¼8.7 Hz, 1H),
3.83B3.88 (m, 1H), 3.64B3.76 (m, 2H), 3.53B3.58 (m, 2H), 3.03B3.21
(m, 3H), 2.61 (s, 3H), 2.43B2.48 (m, 1H), 2.27 (s, 6H), 1.91B2.04 (m, 3H),
1.67B1.84 (m, 4H), 1.52B1.62 (m, 2H), 1.47 (s, 3H), 1.24B1.38 (m, 15H),
1.16 (d, J¼6.8Hz, 3H), 1.01 (d, J¼6.8 Hz, 3H), 0.83 (t, J¼7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): d 215.9, 203.6, 169.5, 157.1, 151.5, 149.6,
144.9, 137.2, 125.1, 124.4, 103.9, 82.1, 79.5, 78.1, 77.1, 70.3, 69.5, 65.9, 60.3,
51.1, 49.6, 49.1, 47.5, 44.8, 42.7, 40.1, 39.4, 38.9, 28.1, 27.4, 24.0, 22.1, 21.1,
19.6, 18.3, 15.7, 14.5, 14.3, 13.8, 10.3. MS (ESI) [M+H]+ m/z 815.0. HRMS
(ESI, m/z) calcd for C41H63N7O10 814.4709, found 814.4715.
Compound 11j
Yield 57.6%. 1H NMR (400MHz, CDCl3): d 8.78 (d, J¼4.7Hz, 1H), 8.24
(d, J¼7.9 Hz, 1H), 7.86 (m, 1H), 7.38 (m, 1H), 4.94 (dd, J¼10.5, 2.2Hz, 1H),
4.68B4.72 (m, 2H), 4.28 (d, J¼7.3 Hz, 1H), 4.25 (d, J¼8.6 Hz, 1H), 3.83
(m, 1H), 3.52B3.65 (m, 4H), 3.06B3.21 (m, 3H), 2.65 (s, 3H), 2.44B2.49
(m, 1H), 2.28 (s, 6H), 2.11B2.16 (m, 2H), 1.93B1.96 (m, 1H), 1.81 (dd,
J¼14.5, 2.1 Hz, 1H), 1.54B1.70 (m, 5H), 1.47 (s, 3H), 1.21B1.35 (m, 15H),
1.08 (d, J¼7.0 Hz, 3H), 1.01 (d, J¼6.9 Hz, 3H), 0.86 (t, J¼7.4 Hz, 3H). 13C
NMR (100MHz, CDCl3): d 216.0, 203.7, 169.6, 164.7, 157.2, 150.3, 147.0,
137.0, 124.6, 122.4, 103.9, 82.1, 79.6, 78.1, 77.2, 70.3, 69.6, 65.9, 60.5, 53.4, 51.2,
49.8, 47.5, 44.9, 43.2, 40.2, 39.5, 39.0, 29.0, 28.2, 26.5, 23.8, 22.3, 21.2, 19.7,
18.4, 15.6, 14.4, 14.3, 13.9, 10.4. MS (ESI) [M+H]+ m/z 829.1. HRMS (ESI,
m/z) calcd for C42H65N7O10 828.4866, found: 828.4878.
Compound 11f
1
Yield 51.5%. H NMR (400MHz, CDCl3): d 8.78 (d, J¼4.7Hz, 1H), 8.24 (d,
J¼7.9Hz, 1H), 7.86 (m, 1H), 7.37 (m, 1H), 4.94 (dd, J¼10.6, 2.1 Hz, 1H),
4.71B4.81 (m, 2H), 4.28 (d, J¼7.3 Hz, 1H), 4.23 (d, J¼8.3 Hz, 1H), 3.83
(q, J¼6.8Hz, 1H), 3.63B3.77 (m, 2H), 3.51B3.58 (m, 2H), 3.04B3.21 (m,
3H), 2.62 (s, 3H), 2.47 (m, 1H), 2.28 (s, 6H), 2.11B2.17 (m, 2H), 1.83B1.97
(m, 1H), 1.55B1.82 (m, 6H), 1.47 (s, 3H), 1.23B1.34 (m, 15H), 1.16 (d,
J¼7.0 Hz, 3H), 1.01 (d, J¼6.9 Hz, 3H), 0.87 (t, J¼7.3 Hz, 3H). 13C NMR
(100 MHz, CDCl3): d 216.0, 203.6, 169.6, 164.7, 157.2, 150.2, 147.0, 136.9,
124.6,122.4, 103.9, 82.2, 79.6, 78.1, 77.3, 70.3, 69.5, 65.9, 52.9, 51.2, 49.8, 47.5,
44.8, 42.6, 40.2, 39.5, 39.0, 28.2, 26.8, 24.1, 22.2, 21.1, 19.7, 18.3, 15.6, 14.6,
14.3, 13.8, 10.4. MS (ESI) [M+H]+ m/z 815.0. HRMS (ESI, m/z) calcd for
C41H63N7O10 814.4709, found 814.4717.
Compound 11k
1
Yield 50.9%. H NMR (400MHz, CDCl3): d 9.38 (s, 1H), 8.70 (d, J¼4.8 Hz,
1H), 8.43 (dt, J¼8.0, 1.9Hz, 1H), 7.41B7.45 (m, 1H), 4.94 (dd, J¼10.5, 2.3 Hz,
1H), 4.65B4.72 (m, 2H), 4.28 (d, J¼7.3Hz, 1H), 4.24 (d, J¼8.7 Hz, 1H), 3.85
(q, J¼6.8 Hz,1H), 3.50B3.70 (m, 4H), 2.99B3.21 (m, 3H), 2.65 (s, 3H),
2.41B2.47 (m, 1H), 2.28 (s, 6H), 2.08B2.16 (m, 2H), 1.93B1.98 (m, 1H),
1.54B1.83 (m, 6H), 1.46 (s, 3H), 1.23B1.33 (m, 15H), 1.16 (d, J¼7.0 Hz, 3H),
1.01 (d, J¼6.9 Hz, 3H), 0.85 (t, J¼7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): d
216.1, 203.7, 169.6, 162.7, 157.2, 151.0, 148.1, 134.2, 123.8, 123.6, 103.9, 82.2,
79.6, 78.2, 70.3, 69.6, 65.9, 60.5, 53.3, 51.2, 49.8, 47.5, 44.5, 43.2, 40.2, 39.5,
39.0, 28.9, 28.2, 26.4,, 23.7, 22.2, 21.2, 19.7, 18.4, 15.7, 14.6, 14.3, 13.9, 10.3. MS
(ESI) [M+H]+ m/z 829.1. HRMS (ESI, m/z) calcd for C42H65N7O10 828.4866,
found 828.4874.
Compound 11g
1
Yield 65.7%. H NMR (400MHz, CDCl3): d 9.36 (s, 1H), 8.69 (d, J¼4.1 Hz,
1H), 8.41 (dt, J¼7.9, 1.7 Hz, 1H), 7.40B7.43 (m, 1H), 4.95 (dd, J¼10.5, 1.8 Hz,
1H), 4.69B4.74 (m, 2H), 4.27 (d, J¼7.3 Hz, 1H), 4.20 (d, J¼8.8 Hz, 1H),
3.64B3.85 (m, 3H), 3.49B3.56 (m, 2H), 3.03B3.19 (m, 3H), 2.61 (s, 3H),
2.41B2.47 (m, 1H), 2.26 (s, 6H), 2.07B2.15 (m, 2H), 1.93B1.98 (m, 1H),
1.54B1.83 (m, 7H), 1.46 (s, 3H), 1.23B1.33 (m, 15H), 1.15 (d, J¼6.9 Hz, 3H),
1.00 (d, J¼6.9Hz, 3H), 0.86 (t, J¼7.2Hz, 3H). 13C NMR (100MHz, CDCl3): d
216.1, 203.6, 169.6, 162.7, 157.3, 151.0, 148.2, 134.2, 123.9, 123.6, 104.0, 82.2,
79.6, 78.2, 70.4, 69.6, 65.9, 60.4, 52.9, 51.2, 49.8, 47.5, 44.5, 42.6, 40.2, 39.6,
39.0, 28.2, 26.8, 24.2, 22.2, 21.2, 19.7, 18.4, 15.6, 14.6, 14.3, 13.9, 10.4. MS (ESI)
[M+H]+ m/z 814.9. HRMS (ESI, m/z) calcd for C41H63N7O10 814.4709, found
814.4700.
Compound 11l
Yield 55.6%. 1H NMR (400MHz, CDCl3): d 8.76 (d, J¼4.8Hz, 2H), 8.02
(d, J¼4.8 Hz, 2H), 4.93 (d, J¼10.2, Hz, 1H), 4.66B4.73 (m, 2H), 4.28
(d, J¼7.3 Hz, 1H), 4.24 (d, J¼8.7 Hz, 1H), 3.82B3.87 (m, 1H), 3.52B3.69
(m, 4H), 3.05B3.21 (m, 3H), 2.65 (s, 3H), 2.44B2.50 (m, 1H), 2.32 (s, 6H),
2.10B2.18 (m, 2H), 1.92B1.98 (m, 1H), 1.81B1.84 (m, 1H), 1.52B1.72
(m, 5H), 1.47 (s, 3H), 1.24B1.36 (m, 15H), 1.16 (d, J¼7.0 Hz, 3H), 1.01
(d, J¼6.8 Hz, 3H), 0.85 (t, J¼7.4Hz, 3H). 13C NMR (100MHz, CDCl3): d
216.1, 203.7, 169.6, 162.7, 157.1, 150.5, 134.9, 120.8, 103.9, 82.2, 79.5, 78.1,
77.2, 70.3, 69.5, 65.8, 60.4, 53.3, 51.2, 49.7, 47.5, 44.9, 43.1, 40.2, 39.5, 39.0,
28.8, 28.2, 26.4, 23.7, 22.2, 21.1, 19.7, 18.3, 15.7, 14.6, 14.3, 13.8, 10.4. MS (ESI)
[M+H]+ m/z 829.1. HRMS (ESI, m/z) calcd for C42H65N7O10 828.4866, found
828.4862.
Compound 11h
Yield 74.1%. 1H NMR (400 MHz, CDCl3): d 8.75 (d, J¼5.3 Hz, 2H), 8.02
(d, J¼5.4 Hz, 2H), 4.92 (d, J¼9.7, Hz, 1H), 4.70B4.79 (m, 2H), 4.28 (d,
J¼7.3Hz, 1H), 4.23 (d, J¼8.7 Hz, 1H), 3.74B3.86 (m, 2H), 3.63B3.70 (m,
1H), 3.52B3.56 (m, 2H), 3.03B3.20 (m, 3H), 2.61 (s, 3H), 2.44B2.49 (m,
1H), 2.27 (s, 6H), 2.06B2.15 (m, 2H), 1.93B1.98 (m, 1H), 1.80B1.84 (m,
Compound 11m
1H), 1.66B1.75 (m, 2H), 1.53B1.62 (m, 2H), 1.47 (s, 3H), 1.24B1.37 (m, Yield 45.2%. 1H NMR (400MHz, CDCl3): d 8.14B8.16 (m, 21H), 7.41B7.49
15H), 1.15 (d, J¼6.9Hz, 3H), 1.01 (d, J¼6.9Hz, 3H), 0.86 (t, J¼7.4 Hz, 3H). (m, 3H), 4.95 (dd, J¼10.5, 2.1Hz, 1H), 4.70B4.78 (m, 2H), 4.26 (d, J¼7.3 Hz,
13C NMR (100 MHz, CDCl3): d 216.1, 203.5, 169.6, 162.9, 157.2, 150.5, 135.0, 1H), 4.18 (d, J¼8.8 Hz, 1H), 3.79B3.85 (m, 2H), 3.67B3.72 (m, 1H), 3.57
120.8, 103.9, 82.2, 79.5, 78.2, 70.3, 69.9, 65.9, 60.4, 52.9, 51.1, 49.7, 47.5, 44.8,
(s, 1H), 3.51B3.54 (m, 1H), 3.01B3.18 (m, 3H), 2.55 (s, 3H), 2.37B2.46
42.6, 40.2, 39.5, 38.9, 28.2, 26.7, 24.1, 22.2, 21.1, 19.7, 18.3, 15.6, 14.6, 14.3, (m, 2H), 2.26 (s, 6H), 1.93B1.98 (m, 1H), 1.79 (dd, J¼14.5, 2.2 Hz, 1H),
13.8, 10.4. MS (ESI) [M+H]+ m/z 814.9. HRMS (ESI, m/z) calcd for 1.51B1.68 (m, 3H), 1.47 (s, 3H), 1.35 (d, J¼6.8 Hz, 3H), 1.21B1.31 (m, 12H),
C41H63N7O10 814.4709, found 814.4711.
1.13 (d, J¼6.9 Hz, 3H), 1.01 (d, J¼6.9 Hz, 3H), 0.87 (t, J¼7.3 Hz, 3H). 13C
The Journal of Antibiotics