Vol. 38, No. 7 (2015)
Biol. Pharm. Bull.
1045
It was obtained from the mixture of 8, cyclohexylamine, m), 3.56–3.64 (8H, m), 5.15 (1H, d, J=17.40Hz), 5.29 (1H,
−
1
K CO and KI, with a yield of 57.3%. IR (KBr) cm : 3435, d, J=10.97Hz), 5.73 (1H, d, J=8.43Hz), 6.41–6.46 (1H, m).
2
3
13
2
928, 2857, 1732, 1645, 1455, 1373, 1290, 1194, 1153, 1117,
011, 911, 801, 727. H-NMR (CDCl ; TMS) δ: 0.65 (3H, 30.37, 34.41, 35.99, 36.64, 41.55, 41.71, 43.90, 44.96, 45.33,
C-NMR (CDCl ) δ: 11.47, 14.83, 16.68, 24.79, 26.33, 26.77,
3
1
1
3
d, J=7.05Hz), 0.82 (3H, d, J=7.03Hz), 1.06–1.11 (6H, m), 45.40, 52.58, 58.11, 59.65, 61.43, 66.82, 68.42, 74.53, 117.26,
+
1
.13–1.20 (4H, m), 1.29–1.32 (1H, m), 1.37 (3H, s), 1.39–1.41 138.99, 167.52, 168.85, 217.05. MS m/z: 574.4 (M ).
(1H, m), 1.47–1.50 (1H, m), 1.52–1.56 (1H, m), 1.57–1.62 (2H,
Mutilin 14-O-1-(4-(N-Methylpiperazinyl)acetyl)piperazine
m), 1.66–1.72 (3H, m), 1.80–1.82 (2H, m), 1.99–2.03 (3H, (9h)
m), 2.11–2.22 (2H, m), 2.27–2.29 (1H, m), 2.35–2.39 (1H,
It was obtained from the mixture of 8, N-methyl piperazine,
−1
m), 2.43–2.56 (4H, m), 3.02 (1H, d, J=17.15Hz), 3.15 (1H, K CO and KI, with a yield of 65.4%. IR (KBr) cm : 3434,
2
3
d, J=17.16Hz), 3.29 (1H, d, J=5.44Hz), 3.37–3.41 (4H, m), 2942, 2880, 2802, 1731, 1627, 1459, 1292, 1191, 1153, 1116,
1
3
.60–3.62 (2H, t), 5.12–5.15 (1H, dd), 5.27–5.29 (1H, dd), 5.73 1012, 983, 915, 830, 727. H-NMR (CDCl ; TMS) δ: 0.65 (3H,
3
1
3
(
1H, d, J=8.48Hz), 6.41–6.46 (1H, m). C-NMR (CDCl ) δ: d, J=6.74Hz), 0.82 (3H, d, J=7.02Hz), 1.04–1.09 (4H, m),
3
1
3
5
0.50, 13.86, 15.72, 23.81, 24.92, 25.35, 25.80, 29.41, 32.04, 1.23 (1H, d, J=16.13Hz), 1.29–1.31 (1H, m), 1.37–1.41 (4H, m),
3.44, 35.04, 35.67, 40.75, 42.93, 43.26, 43.99, 44.44, 46.33, 1.48–1.50 (1H, m), 1.58–1.61 (2H, m), 1.72 (1H, d, J=14.36Hz),
1.43, 51.67, 56.16, 57.15, 58.65, 67.48, 73.56, 116.33, 138.00, 1.98–2.03 (4H, m), 2.13–2.21 (5H, m), 2.27–2.28 (2H, d),
+
167.86, 168.07, 216.04. MS m/z: 586.4 (M ).
2.41–2.52 (9H, m), 3.00 (1H, d, J=17.16Hz), 3.09–3.14 (3H, m),
3.29 (1H, s), 3.58 (3H, s), 5.15 (1H, d, J=17.38Hz), 5.28 (1H,
Mutilin 14-O-1-(4-Pyrrolidinylacetyl)piperazine (9e)
It was obtained from the mixture of 8, pyrrolidine, d, J=10.86Hz), 5.72 (1H, d, J=7.79Hz), 6.41–6.46 (1H, m).
−1
13
K CO and KI, with a yield of 67.2%. IR (KBr) cm : 3420,
C-NMR (CDCl ) δ: 10.50, 13.87, 15.73, 23.83, 25.39, 25.81,
2
3
3
2
932, 2884, 2809, 1733, 1646, 1457, 1374, 1290, 1192, 1153, 29.41, 33.45, 35.03, 35.68, 40.56, 40.75, 42.94, 43.99, 44.35,
1
1117, 1011, 914, 732. H-NMR (CDCl ; TMS) δ: 0.65 (3H, 44.44, 44.93, 51.96, 52.18, 53.96, 57.16, 58.76, 67.45, 73.56,
3
+
d, J=7.06Hz), 0.82 (3H, d, J=7.04Hz), 1.04–1.10 (4H, m), 116.28, 138.05, 166.91, 167.90, 216.10. MS m/z: 587.4 (M ).
1.18–1.23 (2H, t), 1.28–1.32 (1H, m), 1.37 (3H, s), 1.39–1.41
Mutilin 14-O-1-(4-Anilinoacetyl)piperazine (9i)
(
1H, m), 1.47–1.50 (1H, m), 1.56–1.62 (2H, m), 1.69–1.72 (1H,
It was obtained from the mixture of 8, aniline, K CO and
2
3
−1
m), 1.76–1.78 (4H, m), 2.00–2.03 (2H, m), 2.11–2.20 (2H, m), KI, with a yield of 68.5%. IR (KBr) cm : 3396, 2960, 2862,
.27–2.29 (1H, t), 2.40–2.53 (4H, m), 2.65 (4H, s), 3.02 (1H, d, 1734, 1654, 1648, 1604, 1508, 1443, 1420, 1261, 1193, 1152,
2
1
J=17.13Hz), 3.14 (1H, d, J=17.14Hz), 3.30 (1H, d, J=6.45Hz), 1114, 1014, 911, 804, 750, 730, 692. H-NMR (CDCl ; TMS)
3
3
.36 (2H, s), 3.53–3.54 (2H, t), 3.58 (2H, s), 5.12–5.15 (1H, δ: 0.66 (3H, d, J=6.98Hz), 0.82 (3H, d, J=6.87Hz), 1.04–1.10
dd), 5.26–5.28 (1H, dd), 5.73 (1H, d, J=8.46Hz), 6.41–6.46 (4H, m), 1.19–1.23 (3H, m), 1.29–1.32 (1H, m), 1.37–1.41 (5H,
1
3
(
2
1H, m). C-NMR (CDCl ) δ: 10.51, 13.87, 15.72, 22.87, 23.83, s), 1.58–1.61 (2H, m), 1.72 (1H, d, J=13.05Hz), 1.99–2.03
3
5.38, 25.81, 29.41, 33.45, 35.04, 35.69, 40.51, 40.75, 42.94, (2H, m), 2.10–2.22 (2H, m), 2.27–2.29 (1H, m), 2.48–2.61
4
3.99, 44.13, 44.45, 51.56, 56.36, 57.16, 58.70, 67.46, 73.56, (4H, m), 3.05 (1H, d, J=17.18Hz), 3.17 (1H, d, J=17.18Hz),
+
116.29, 138.04, 166.59, 167.90, 216.102. MS m/z: 558.7 (M ).
3.28–3.31 (1H, m), 3.43–3.45 (2H, m), 3.67 (2H, s), 3.80 (2H,
Mutilin 14-O-1-(4-Piperidylacetyl)piperazine (9f)
s), 5.15 (1H, d, J=17.39Hz), 5.29 (1H, d, J=10.98Hz), 5.74 (1H,
It was obtained from the mixture of 8, piperidine, K CO
d, J=8.46Hz), 6.41–6.46 (1H, m), 6.56 (2H, d, J=7.98Hz),
2
3
−1
13
and KI, with a yield of 62.9%. IR (KBr) cm : 3446, 2934, 6.64–6.67 (1H, t), 7.11–7.13 (2H, t). C-NMR (CDCl ) δ:
3
2
8
0
860, 1733, 1635, 1456, 1373, 1304, 1192, 1154, 1118, 1012, 914, 10.50, 13.85, 15.72, 23.83, 25.36, 25.80, 29.39, 33.43, 35.04,
1
62, 797. H-NMR (CDCl ; TMS) δ: 0.73 (3H, d, J=7.05Hz), 35.66, 40.74, 40.84, 42.93, 43.99, 44.11, 44.43, 51.54, 57.14,
3
.89 (3H, d, J=7.02Hz), 1.13–1.17 (4H, m), 1.30 (1H, d, 58.55, 67.55, 73.56, 111.94, 116.33, 116.58, 128.26, 138.00,
+
J=15.92Hz), 1.36–1.39 (1H, m), 1.42–1.47 (7H, m), 1.55–1.57 146.28, 166.41, 167.76, 216.03. MS m/z: 580.8 (M ).
(
5H, m), 1.63–1.69 (3H, m), 1.76–1.79 (1H, m), 2.06–2.10 (2H,
m), 2.18–2.29 (2H, m), 2.34–2.36 (1H, t), 2.44–2.48 (4H, m), RESULTS AND DISCUSSION
.51–2.60 (4H, m), 3.06 (1H, d, J=17.08Hz), 3.14 (1H, s), 3.21
1H, d, J=17.09Hz), 3.34–3.37 (1H, m), 3.65–3.68 (4H, m),
2
(
Tested Strains Staphylococcus aureus (S. aureus)
5
6
2
.19–5.22 (1H, dd), 5.34–5.35 (1H, d), 5.80 (1H, d, J=8.48Hz), ATCC25923, S. aureus CMCC26003, Staphylococcus epider-
13
.49–6.54 (1H, m). C-NMR (CDCl ) δ: 11.50, 14.90, 16.72, midis (S. epidermidis) ATCC12228, Enterococcus faecalis (E.
3.93, 24.86, 25.95, 26.41, 26.84, 30.45, 34.47, 36.07, 36.72, faecalis) ATCC19433, Streptococcus suis (S. suis) ATCC43765,
3
41.60, 41.79, 43.97, 45.05, 45.47, 52.77, 53.28, 54.31, 58.19, Streptococcus agalactiae (S. agalactiae) ATCC13813, Esche-
5
9.84, 68.45, 74.58, 117.24, 139.09, 168.39, 168.93, 217.00. MS richia coli (E. coli) CVCC231, and methicillin-resistant S. au-
+
m/z: 572.4 (M ).
reus (MRSA) were obtained from Neimeng Province, China.
Bioassay The in vitro antibacterial activities of the
Mutilin 14-O-1-(4-Morpholinylacetyl)piperazine (9g)
It was obtained from the mixture of 8, morpholine, compounds were evaluated against a panel of Gram-positive
−1
K CO and KI, with a yield of 61.7%. IR (KBr) cm : 3480, pathogens (S. aureus, MRSA, S. epidermidis, E. faecalis, S.
2
3
2
929, 2810, 1733, 1634, 1609, 1457, 1290, 1191, 1150, 1117, suis, and S. agalactiae) and a Gram-negative pathogen (E.
1
1011, 908, 864. H-NMR (CDCl ; TMS) δ: 0.66 (3H, d, coli) with erythromycin and tiamutilin as reference drugs via
3
J=6.97Hz), 0.82 (3H, d, J=6.89Hz), 1.04–1.10 (4H, m), 1.23 the broth micro dilution method based on the National Com-
(
1H, d, J=15.99Hz), 1.29–1.31 (1H, m), 1.37–1.42 (5H, m), mittee for Clinical Laboratory Standards (NCCLS). The mini-
.45–1.52 (2H, m), 1.72 (2H, d, J=14.18Hz), 1.99–2.03 (2H, mum inhibitory concentration (MIC) data are listed in Table
m), 2.10–2.22 (2H, m), 2.25–2.30 (1H, m), 2.43–2.55 (8H, m), 1. The results clearly showed that most of the compounds
.02 (1H, d, J=17.14Hz), 3.10–3.15 (3H, m), 3.28–3.30 (1H, exhibited moderate to good antibacterial activities. Those
1
3