Synthesis and antibacterial activity of 400-O-carbamates
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400-O-((benzyl)carbamoyl)erythromycin A 6,9-imino ether
11,12-cyclic carbonate (5e)
400-O-((propenyl)carbamoyl)erythromycin A 6,9-imino ether
11,12-cyclic carbonate (5i)
White solid, yield: 76.5%, m.p.: 124–127 1C, TLC RF¼0.51 (dichloromethane– White solid, yield: 71.8%, m.p.: 112–115 1C, TLC RF¼0.52 (dichloromethane–
methanol, 10:1); IR (KBr): 3265, 2974, 2936, 1805, 1767, 1726, 1657, 1510, methanol, 10:1); IR (KBr): 3319, 2975, 2936, 1805, 1724, 1659, 1522, 1457,
1455, 1383, 1350, 1244, 1167, 1109, 1081, 1015cm–1; 1H NMR (600MHz, 1384, 1245, 1167, 1109, 1075, 1046, 1015 cm–1; 1H NMR (600 MHz, CDCl3): d
CDCl3) d 7.28–7.26 (m, 5H), 5.31–5.30 (m, 1H), 4.88 (dd, J¼9.0 Hz, J¼3.0 Hz, 5.85 (s, 1H), 5.26–5.09 (m, 3H), 4.88–4.86 (m, 1H), 4.55–4.50 (m, 2H), 4.45 (d,
1H), 4.59–4.55 (m, 1H), 4.34–4.25 (m, 2H), 4.23–4.20 (m, 2H), 4.19–4.18 (m, J¼7.2 Hz, 1H), 4.40–4.35 (m, 3H), 3.91–3.71 (m, 2H), 3.59–3.57 (m, 1H), 3.36
1H), 3.75–3.70 (m, 2H), 3.52–3.51 (m, 1H) 3.43–3.40 (m, 1H), 3.30–3.28 (m, (s, 3H), 3.05–2.96 (m, 3H), 2.92–2.64 (m, 8H), 2.16–2.00 (m, 2H), 1.79–1.76
3H), 2.89–2.88 (m, 1H), 2.88–2.83 (m, 2H), 2.44–2.41 (m, 2H), 2.41–2.31 (m, 3H), 1.63–1.51 (m, 7H), 1.34–1.28 (m, 6H), 1.28–1.08 (m, 12H), 0.9–0.83
(m, 6H), 1.95–1.85 (m, 2H), 1.70–1.68 (m, 1H), 1.65–1.61 (m, 1H), 1.56–1.48 (m, 9H); ESI-MS m/z calculated for C42H69N3O14 839.5, found [M+H]+ 841.1;
(m, 5H), 1.47–1.42 (m, 2H), 1.38–1.33 (m, 1H), 1.31–1.23 (m, 3H), 1.27–1.23 HR-MS (ESI) m/z calculated for C42H69N3O14 [M+H]+: 840.0091, found
(m, 6H), 1.23–1.17 (m, 6H), 1.15–1.10 (m, 3H), 1.09–0.92 (m, 9H); ESI-MS 840.1038.
m/z calculated for C46H71N3O14 889.5, found [M+H]+ 890.9; HR-MS (ESI)
m/z calculated for C46H71N3O14 [M+H]+: 890.0678, found 890.0816.
ACKNOWLEDGEMENTS
This research was supported by National Natural Science Foundation of China
400-O-((phenethyl)carbamoyl)erythromycin A 6,9-imino ether
11,12-cyclic carbonate (5f)
(21072114 and 20872081), Major R&D Program of New Drugs—National S&T
Key Special Subject of China (2009ZX09103-115) and the Project-sponsored by
SRF for ROCS, SEM.
White solid, yield: 83.5%, m.p.: 120–123 1C, TLC RF¼0.52 (dichloromethane–
methanol, 10:1); IR (KBr): 3342, 2974, 2936, 1810, 1727, 1665, 1498, 1455,
1381, 1337, 1245, 1169, 1111, 1073, 1016 cm–1; 1H NMR (600MHz, CDCl3): d
7.28–7.26 (m, 3H), 7.21–7.18 (m, 2H), 5.31–5.30 (m, 1H), 4.88 (dd, J¼4.0 Hz,
J¼4.8Hz, 1H), 4.60–4.59 (m, 1H), 4.34–4.25 (m, 2H), 4.24–4.22 (m, 2H),
1
2
3
4
Jones, W. R., Nichols, R. L. & Finland, M. Development of resistance and cross-
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4.20–4.18 (m, 1H), 3.78–3.76 (m, 2H), 3.52–3.51 (m, 1H), 3.29–3.28 (m, 3H),
2.97–2.96 (m, 1H), 2.89–2.88 (m, 3H), 2.44–2.41 (m, 1H), 2.31–2.25 (m, 8H),
1.95–1.85 (m, 2H), 1.70–1.67 (m, 2H), 1.61–1.56 (m, 5H), 1.48–1.42 (m, 2H),
1.38–1.33 (m, 1H), 1.33–1.31 (m, 6H), 1.26–1.23 (m, 3H), 1.18–1.13 (m, 6H),
1.11–1.08 (m, 3H), 1.07–0.92 (m, 9H); ESI-MS m/z calculated for
C47H73N3O14: 903.5, found [M+H]+ 904.9; HR-MS (ESI) m/z calculated for
C47H73N3O14 [M+H]+: 904.0943, found 904.1084.
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400-O-((isopropyl)carbamoyl)erythromycin A 6,9-imino ether
11,12-cyclic carbonate (5g)
5
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White solid, yield: 72.7%, m.p.: 121–124 1C, TLC RF¼0.53 (dichloromethane–
methanol, 10:1); IR (KBr): 3342, 3026, 2974, 2936, 1810, 1727, 1655, 1598,
1455, 1381, 1337, 1245, 1169, 1111, 1073, 1016cm–1; 1H NMR (600MHz,
CDCl3): d 5.18–5.16 (m, 1H), 4.88 (dd, J¼9.0 Hz, J¼3 .0Hz, 1H), 4.50–4.48
(m, 1H), 4.30–4.26 (m, 3H), 4.18–4.16 (m, 1H), 3.80–3.72 (m, 2H), 3.47–3.41
(m, 4H), 2.88–2.83 (m, 1H), 2.81–2.77 (m, 1H), 2.67–2.54 (m, 2H), 2.52–2.48
(m, 6H), 2.18–2.10 (m, 1H), 1.94–1.90 (m, 2H), 1.79–1.74 (m, 2H), 1.66–1.56
(m, 3H), 1.54–1.50 (m, 2H ), 1.47–1.45 (m, 2H), 1.44–1.42 (m, 1H), 1.29–1.27
(m, 6H), 1.25–1.17 (m, 9H), 1.20–1.16 (m, 3H), 1.16–1.09 (m, 3H), 1.07–1.04
(m, 3H), 1.04–0.94 (m, 6H), 0.93–0.92 (m, 3H); ESI-MS m/z calculated for
C42H71N3O14 841.5, found [M+H]+ 843.0; HR-MS (ESI) m/z calculated for
C42H71N3O14 [M+H]+: 842.0250, found 842.0532.
7
Weisblum, B. Erythromycin resistance by ribosome modification. Antimicrob. Agents
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400-O-((butyl)carbaomoyl)erythromycin A 6,9-imino ether
11,12-cyclic carbonate (5h)
White solid, yield: 81.3%, m.p.: 115–118 1C, TLC RF¼0.53 (dichloromethane–
methanol, 10:1); IR (KBr): 3304, 2968, 2934, 2874, 1807, 1727, 1656, 1522,
1459, 1383, 1246, 1168, 1109, 1055, 1014 cm–1; 1H NMR (600MHz, CDCl3): d
5.15–5.13 (m, 1H), 4.95 (dd, J¼9.0 Hz, J¼3.6 Hz, 1H), 4.52–4.50 (m, 1H),
4.30–4.26 (m, 3H), 3.78–3.76 (m, 2H), 3.45–3.44 (m, 1H), 3.30–3.28 (m, 3H),
3.28–3.20 (m, 2H), 2.81–2.75 (m, 3H), 2.38–2.35 (m, 6H), 2.18–2.14 (m, 2H),
1.82–1.80 (m, 2H), 1.73–1.70 (m, 2H), 1.65–1.55 (m, 5H), 1.54–1.48 (m, 4H),
1.40–1.35 (m, 3H), 1.33–1.29 (m, 6H), 1.27–1.22 (m, 9H), 1.19–1.15 (m, 3H),
1.12–1.08 (m, 3H), 1.08–1.06 (m, 3H), 0.96–0.87 (m, 6H); ESI-MS m/z
calculated for C43H73N3O14 855.5, found [M+H]+ 856.8; HR-MS (ESI) m/z
calculated for C43H73N3O14 [M+H]+: 856.0515, found 856.0768.
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The Journal of Antibiotics