Vol. 40, No. 8 (2017)
Biol. Pharm. Bull.
1169
1
H-NMRꢀ (CDCl ) δ:ꢀ 10.16ꢀ (s,ꢀ 1H),ꢀ 8.44–8.26ꢀ (m,ꢀ 2H),ꢀ 8.12ꢀ 134.92, 130.71, 120.22, 117.64, 115.63, 111.47, 73.10, 69.99,
3
(
1
d, J=6.9ꢀHz,ꢀ 2H),ꢀ 6.86ꢀ (s,ꢀ 1H),ꢀ 6.48ꢀ (dd,ꢀ J=17.4, 11.1Hz, 57.76, 45.46, 44.52, 44.22, 41.96, 36.87, 34.48, 33.81, 31.62,
H), 5.76 (d, J=8.0Hz, 1H), 5.35 (d, J=11.0Hz, 1H), 5.21 (d, 30.61, 30.31, 29.02, 27.05, 24.96, 16.62, 15.07, 12.01. IR (KBr)
−1
J=17.5ꢀHz,ꢀ1H),ꢀ3.79ꢀ(s,ꢀ2H),ꢀ3.42–3.30ꢀ(m,ꢀ1H),ꢀ3.05ꢀ(s,ꢀ2H),ꢀ cm :ꢀ 3446,ꢀ 3247,ꢀ 2952,ꢀ 1731,ꢀ 1646,ꢀ 1540,ꢀ 1463,ꢀ 1262,ꢀ 1114,ꢀ
.39–2.29 (m, 1H), 2.28–2.15 (m, 2H), 2.15–2.03 (m, 2H), 1.77 1017, 802, 756. δ:ꢀ 217.64,ꢀ 168.66,ꢀ 164.60,ꢀ 157.82,ꢀ 147.62,ꢀ
d, J=13.1Hz, 3H), 1.64 (dd, J=21.2, 11.7Hz, 2H), 1.58–1.49 141.39, 134.92, 130.71, 120.22, 117.64, 115.63, 111.47, 73.10,
2
(
(m, 2H), 1.49–1.41 (m, 4H), 1.41–1.21 (m, 4H), 1.21–1.05 (m, 69.99, 57.76, 45.46, 44.52, 44.22, 41.96, 36.87, 34.48, 33.81,
13
4
H), 0.88 (d, J=6.4Hz, 3H), 0.72 (d, J=6.6Hz, 3H). C-NMR 31.62, 30.61, 30.31, 29.02, 27.05, 24.96, 16.62, 15.07, FAB-MS
−
(
1
CDCl ) δ:ꢀ 216.98,ꢀ 168.59,ꢀ 162.57,ꢀ 158.14,ꢀ 150.33,ꢀ 146.66,ꢀ m/z:ꢀ625.2387ꢀ[M−H] (Calcd for C H N O S :ꢀ625.2406).
3
33 41
2
6 2
39.18, 137.32, 128.64, 124.20, 117.18, 111.88, 74.65, 69.41,
14-O-(3-Aminobenzamide-thiazolyl)-4-methyl
Thioether
5
8.17, 45.44, 44.84, 43.93, 41.75, 36.74, 36.02, 34.43, 32.96, Mutilin (13h)
1
31.55, 30.40, 26.85, 26.42, 24.84, 16.86, 14.92, 11.50. IR (KBr)
Whiteꢀfoamꢀsolid;ꢀyield:ꢀ40%;ꢀmpꢀ108.5–110.4°C.ꢀ H-NMR
−1
cm :ꢀ 3450,ꢀ 3253,ꢀ 2932,ꢀ 1727,ꢀ 1676,ꢀ 1548,ꢀ 1528,ꢀ 1346,ꢀ 1288,ꢀ (CDCl ) δ:ꢀ7.26ꢀ(t,ꢀJ=5.3Hz, 2H), 7.23–7.19 (m, 1H), 6.87 (dd,
3
1
(
115, 1015, 980, 850, 713. FAB-MS m/z:ꢀ 654.2286ꢀ [M−H]− J=7.1,ꢀ 1.7ꢀHz,ꢀ 1H),ꢀ 6.80ꢀ (s,ꢀ 1H),ꢀ 6.49ꢀ (dd,ꢀ J=17.4, 11.0Hz,
Calcd for C H N O S :ꢀ654.2308). 1H), 5.76 (d, J=8.4Hz, 1H), 5.35 (d, J=11.0Hz, 1H), 5.21 (dd,
4-O-(2,4-Dichlorobenzamide-thiazolyl)-4-methylꢀ J=17.4,ꢀ 1.4ꢀHz,ꢀ 1H),ꢀ 3.80ꢀ (s,ꢀ 2H),ꢀ 3.36ꢀ (s,ꢀ 1H),ꢀ 3.05ꢀ (s,ꢀ 2H),ꢀ
Thioether Mutilin (13f) 2.41–2.30 (m, 1H), 2.28–2.14 (m, 2H), 2.14–2.04 (m, 2H), 1.76
Whiteꢀfoamꢀsolid;ꢀyield:ꢀ46%;ꢀmpꢀ102.5–104.1°C.ꢀ H-NMR (d, J=14.3Hz, 1H), 1.69–1.59 (m, 3H), 1.59–1.50 (m, 1H),
CDCl ) δ:ꢀ7.82ꢀ(d,ꢀJ=8.4Hz, 1H), 7.50 (d, J=2.0Hz, 1H), 7.39 1.48–1.40 (m, 4H), 1.39–1.30 (m, 2H), 1.19–1.06 (m, 4H), 0.88
33
43
3
7 2
1
1
(
3
13
(
1
dd, J=8.4,ꢀ2.0ꢀHz,ꢀ1H),ꢀ6.85ꢀ(s,ꢀ1H),ꢀ6.48ꢀ(dd,ꢀJ=17.4, 11.0Hz, (d, J=7.0Hz, 3H), 0.73 (d, J=6.9Hz, 3H). C-NMRꢀ (CDCl3)
H), 5.76 (d, J=8.5Hz, 1H), 5.35 (d, J=11.0Hz, 1H), 5.21 (dd, δ:ꢀ216.99,ꢀ168.63,ꢀ164.60,ꢀ158.67,ꢀ147.15,ꢀ146.39,ꢀ139.14,ꢀ132.87,ꢀ
J=17.4,ꢀ 1.4ꢀHz,ꢀ 1H),ꢀ 3.78ꢀ (s,ꢀ 2H),ꢀ 3.36ꢀ (s,ꢀ 1H),ꢀ 3.06ꢀ (s,ꢀ 2H),ꢀ 129.89, 119.28, 117.21, 116.59, 113.82, 111.33, 74.64, 69.29,
.40–2.30 (m, 1H), 2.30–2.15 (m, 2H), 2.14–2.03 (m, 2H), 1.77 58.18, 45.44, 44.83, 43.92, 41.75, 36.77, 36.01, 34.44, 32.93,
dd, J=14.3, 2.8Hz, 1H), 1.69–1.61 (m, 2H), 1.61–1.48 (m, 2H), 31.66, 30.41, 26.84, 26.40, 24.84, 16.85, 14.94, 11.49. IR (KBr)
2
(
1
−1
.48–1.41 (m, 4H), 1.40–1.29 (m, 2H), 1.20–1.06 (m, 4H), 0.88 cm :ꢀ 3455,ꢀ 3370,ꢀ 3235,ꢀ 2929,ꢀ 1727,ꢀ 1667,ꢀ 1541,ꢀ 1456,ꢀ 1280,ꢀ
13
−
(
d, J=7.0Hz, 3H), 0.73 (d, J=6.9Hz, 3H). C-NMRꢀ (CDCl3) 1115, 1017, 941, 844, 744. FAB-MS m/z:ꢀ 626.2730ꢀ [M−H]
δ:ꢀ 216.87,ꢀ 168.58,ꢀ 162.32,ꢀ 157.65,ꢀ 146.88,ꢀ 139.17,ꢀ 138.65,ꢀ (Calcd for C H N O S :ꢀ626.2722).
33
44
3
5 2
1
6
3
32.13, 132.04, 130.65, 130.25, 127.94, 117.15, 111.70, 74.64,
9.34, 58.18, 45.44, 44.86, 43.94, 41.76, 36.76, 36.03, 34.42, Mutilin (13i)
3.03, 31.54, 30.42, 26.85, 26.41, 24.84, 16.83, 14.92, 11.44. IR
14-O-(4-Aminobenzamide-thiazolyl)-4-methyl
Thioether
1
Whiteꢀ solid;ꢀ yield:ꢀ 16.4%;ꢀ mpꢀ 134.8–137.4°C.ꢀ H-NMR
−1
(
1
6
KBr) cm :ꢀ 3449,ꢀ 3256,ꢀ 3193,ꢀ 3080,ꢀ 2960,ꢀ 2927,ꢀ 1728,ꢀ 1676,ꢀ (CDCl ) δ:ꢀ 7.78ꢀ (d,ꢀ J=7.2ꢀHz,ꢀ 2H),ꢀ 6.76ꢀ (s,ꢀ 1H),ꢀ 6.69ꢀ (d,ꢀ
541, 1454, 1284, 1262, 1103, 1018, 802, 697. FAB-MS m/z:ꢀ J=7.2Hz, 2H), 6.48 (dd, J=17.0, 11.1Hz, 1H), 5.76 (d,
77.1660ꢀ[M−H] (Calcd for C H N O S Cl :ꢀ677.1677).
3
−
J=8.3Hz, 1H), 5.36 (d, J=11.0Hz, 1H), 5.21 (d, J=17.4Hz,
33
39
2
5
2
2
1
4-O-(2-Hydroxylbenzamide-thiazolyl)-4-methyl Thioether 1H),ꢀ 3.80ꢀ (s,ꢀ 2H),ꢀ 3.36ꢀ (s,ꢀ 1H),ꢀ 3.04ꢀ (s,ꢀ 2H),ꢀ 2.39–2.29ꢀ (m,ꢀ
Mutilin (13g) 1H), 2.29–2.15 (m, 2H), 2.14–2.04 (m, 2H), 1.76 (d, J=14.2Hz,
Whiteꢀ solid;ꢀ yield:ꢀ 37.7%;ꢀ mpꢀ 218.5–220.1°C.ꢀ H-NMR 1H), 1.64 (dd, J=21.4, 10.6Hz, 2H), 1.56 (d, J=12.9Hz, 1H),
CDCl ) δ:ꢀ7.64ꢀ(d,ꢀJ=8.0Hz, 1H), 7.46 (t, J=7.7Hz, 1H), 7.03 1.52–1.40 (m, 5H), 1.40–1.29 (m, 2H), 1.19–1.06 (m, 4H), 0.87
1
(
3
13
(
d, J=8.4Hz, 1H), 6.94 (t, J=7.6ꢀHz,ꢀ 1H),ꢀ 6.85ꢀ (s,ꢀ 1H),ꢀ 6.48ꢀ (d, J=6.4Hz, 3H), 0.73 (d, J=6.2Hz, 3H). C-NMRꢀ(CDCl3)
(dd, J=17.4, 11.0Hz, 1H), 5.76 (d, J=8.4Hz, 1H), 5.35 (d, δ:ꢀ216.97,ꢀ168.61,ꢀ164.02,ꢀ159.63,ꢀ151.00,ꢀ145.47,ꢀ139.14,ꢀ129.55,ꢀ
J=11.0Hz, 1H), 5.21 (d, J=17.3ꢀHz,ꢀ1H),ꢀ3.82ꢀ(s,ꢀ2H),ꢀ3.41–3.32ꢀ 120.65, 117.22, 114.25, 111.00, 74.64, 69.29, 58.19, 45.44, 44.83,
(
2
4
1
3
m,ꢀ 1H),ꢀ 3.05ꢀ (s,ꢀ 2H),ꢀ 2.40–2.30ꢀ (m,ꢀ 1H),ꢀ 2.28–2.17ꢀ (m,ꢀ 2H),ꢀ 43.92, 41.74, 36.77, 36.01, 34.44, 32.88, 31.43, 30.42, 26.84,
−1
.17–2.04 (m, 2H), 1.76 (d, J=14.2Hz, 2H), 1.70–1.59 (m, 26.39, 24.84, 16.86, 14.93, 11.50. IR (KBr) cm :ꢀ 3466,ꢀ 3362,ꢀ
H), 1.58–1.49 (m, 2H), 1.49–1.41 (m, 4H), 1.39–1.29 (m, 2H), 3231, 2926, 1724, 1624, 1540, 1282, 1182, 1016, 734. FAB-MS
−
.20–1.07 (m, 4H), 0.88 (d, J=7.0Hz, 3H), 0.73 (d, J=6.9Hz, m/z:ꢀ624.2585ꢀ[M−H] (Calcd for C H N O S :ꢀ624.2566).
H). δ:ꢀ11.9ꢀ(s,ꢀ1H),ꢀ11.65ꢀ(s,ꢀ1H),ꢀ7.96ꢀ(d,ꢀJ=7.8Hz, 1H), 7.44
33
42
3
5 2
14-O-(2-Furoyl-thiazolyl)-4-methyl Thioether Mutilin (13j)
Whiteꢀ foamꢀ solid;ꢀ yield:ꢀ 50%;ꢀ mpꢀ 105.8–107.2°C.ꢀ
H-NMRꢀ (CDCl ) δ:ꢀ 9.84ꢀ (s,ꢀ 1H),ꢀ 7.59–7.45ꢀ (m,ꢀ 1H),ꢀ 7.31ꢀ
(
s,ꢀ1H),ꢀ6.97ꢀ(d,ꢀJ=10.7Hz, 3H), 6.13 (d, J=11.2Hz, 1H), 5.54
1
(d, J=8.1Hz, 1H), 5.05 (d, J=8.2Hz, 2H), 4.46 (d, J=5.5Hz,
3
1
H),ꢀ 3.79ꢀ (s,ꢀ 2H),ꢀ 3.4ꢀ (s,ꢀ 1H),ꢀ 2.37ꢀ (s,ꢀ 1H),ꢀ 2.33–1.94ꢀ (m,ꢀ (d, J=3.6ꢀHz,ꢀ 1H),ꢀ 6.78ꢀ (s,ꢀ 1H),ꢀ 6.56ꢀ (dd,ꢀ J=3.5, 1.7Hz, 1H),
H), 1.7–1.53 (m, 2H), 1.52–1.32 (m, 5H), 1.31–1.18 (m, 5H), 6.46 (dd, J=17.4, 11.0Hz, 1H), 5.74 (d, J=8.4Hz, 1H), 5.32
4
1
3
.07–0.92 (m, 4H), 0.8 (d, J=8Hz, 3H), 0.61 (d, J=6.5Hz, (d, J=11.0Hz, 1H), 5.19 (dd, J=17.4,ꢀ1.4ꢀHz,ꢀ1H),ꢀ3.79ꢀ(s,ꢀ2H),ꢀ
1
H). H-NMRꢀ(DMSO-d ):ꢀ δ:ꢀ11.9ꢀ(s,ꢀ1H),ꢀ11.65ꢀ(s,ꢀ1H),ꢀ7.96ꢀ 3.39–3.29ꢀ(m,ꢀ1H),ꢀ3.03ꢀ(s,ꢀ2H),ꢀ2.37–2.28ꢀ(m,ꢀ1H),ꢀ2.28–2.12ꢀ
6
(
(
2
1
1
0
1
5
3
d, J=7.8ꢀHz,ꢀ 1H),ꢀ 7.44ꢀ (s,ꢀ 1H),ꢀ 6.97ꢀ (d,ꢀ J=10.7Hz, 3H), 6.13 (m, 2H), 2.11–2.01 (m, 2H), 1.74 (dd, J=14.5, 2.4Hz, 1H),
d, J=11.2Hz, 1H), 5.54 (d, J=8.1Hz, 1H), 5.05 (d, J=8.2Hz, 1.68–1.57 (m, 3H), 1.57–1.47 (m, 1H), 1.47–1.37 (m, 4H),
H), 4.46 (d, J=5.5ꢀHz,ꢀ1H),ꢀ3.79ꢀ(s,ꢀ2H),ꢀ3.4ꢀ(s,ꢀ1H),ꢀ2.37ꢀ(s,ꢀ 1.38–1.26 (m, 2H), 1.18–1.04 (m, 4H), 0.86 (d, J=7.0Hz, 3H),
13
H), 2.33–1.94 (m, 4H), 1.7–1.53 (m, 2H), 1.52–1.32 (m, 5H), 0.70 (d, J=6.8Hz, 3H). C-NMRꢀ (CDCl ) δ:ꢀ 216.99,ꢀ 168.58,ꢀ
3
.31–1.18 (m, 5H), 1.07–0.92 (m, 4H), 0.8 (d, J=8Hz, 3H), 157.58, 155.05, 146.64, 145.82, 145.52, 139.20, 117.10, 117.07,
1
3
.61 (d, J=6.5Hz, 3H). C-NMRꢀ (CDCl ) δ:ꢀ 216.98,ꢀ 168.60,ꢀ 112.88, 111.42, 74.60, 69.30, 58.18, 45.43, 44.83, 43.92, 41.73,
3
39.14, 135.54, 119.67, 118.72, 117.21, 111.86, 74.65, 69.38, 36.75, 36.02, 34.42, 32.91, 31.65, 30.40, 26.82, 26.49, 24.82,
8.18, 45.44, 44.84, 43.92, 41.74, 36.75, 36.01, 34.43, 32.96, 16.81, 14.91, 11.47. IR (KBr) cm :ꢀ 3447,ꢀ 3410,ꢀ 2933,ꢀ 1728,ꢀ
1.53, 30.41, 26.84, 26.39, 24.84, 16.87, 14.93, 11.50. C-NMR 1671, 1588, 1541, 1328, 1296, 1115, 1015, 856, 759. FAB-MS
DMSO-d ) δ:ꢀ 217.64,ꢀ 168.66,ꢀ 164.60,ꢀ 157.82,ꢀ 147.62,ꢀ 141.39,ꢀ m/z:ꢀ599.2243ꢀ[M−H] (Calcd for C H N O S :ꢀ599.2250).
−1
13
−
(
6
31 39
2
6 2