356 JOURNAL OF CHEMICAL RESEARCH 2010
saturated salt water (10 mL), dried with sodium sulfate and evaporated
in vacuo to give the crude product. The crude product was chromato-
graphed on silica gel using petroleum ether/ethyl acetate (2:1) as
eluent to afford a yellow solid 0.36 g (yield 58%).
1528, 1456, 1420, 1400, 1348, 1288, 1115, 718, 619; Calcd for
C33H46N2O7S (%): C, 64.47; H, 7.54; N, 4.56; S, 5.22. Found: C, 64.30;
H, 7.52; N, 4.59; S, 5.21%; X-ray: amorphism; HR-MS (ESI): Calcd
for C33H46N2O7S (M-H+): 613.2943; Found 613.2955.
Mutilin 14-O-[1-(5-nitro-2-chloro)benzamide-2-methylpropane-2-
yl]thioacetate (11e): Buff solid (93%); melting point: 66–68 °C; H
1
Preparation of 12c-e; general procedure
A mixture of compounds 11c–e (0.67 mmol), iron (1.96 mmol) and
ammonium chloride (5.89 mmol) in 80% ethanol (7.5 mL) was heated
at 45 °C for 2h, filtered and the cake was washed with ethanol. The
filtrate was extracted with ethyl acetate (3 × 15 mL) and the extract
was washed with water (3 × 10 mL) and 2N HCl (3×5 mL). Then
the ethyl acetate layer was extracted with 6N HCl (6 × 4 mL), and
the water layer was evaporated in vacuo to afford a solid (yield
51–58%).
Mutilin 14-O-[1-benzamide-2-methylpropane-2-yl]thioacetate (11a):
White solid (50%); melting point: 62–63 °C; 1H NMR spectrum (400
MHz; d1-CDCl3; TMS): δ (ppm) = 7.92 (1H, d, J = 7.6 Hz), 7.46–7.55
(4H, m), 6.42 (1H, dd, J1 = 14.0 Hz, J2 = 10.4 Hz), 5.74 (1H, d, J = 7.6
Hz), 5.13 (1H, d, J = 13.6 Hz), 5.12 (1H, d, J = 10.4 Hz), 3.29–3.51
(2H, m), 3.34 (1H, d, J = 6.4 Hz), 3.27 (1H, d, J = 16.8 Hz), 3.19 (1H,
d, J = 16.4 Hz), 2.28–2.32 (1H, m), 2.24–2.26 (1H, m), 2.16–2.22
(1H, m), 2.10 (1H, s), 2.05–2.12 (1H, m), 1.74–1.80 (1H, m), 1.57–
1.71 (3H, m), 1.46 (3H, s), 1.42–1.53 (2H, m), 1.33–1.34 (1H, m),
1.34 (3H, s), 1.31 (3H, s), 1.14 (3H, s), 1.09–1.17 (1H, m), 0.87 (3H,
d, J = 6.8 Hz), 0.73 (3H, d, J = 7.2 Hz); IR (KBr, cm−1) 3414, 3080,
2928, 2860, 1728, 1652, 1600, 1537, 1458, 1381, 1286, 1115, 805,
713, 619;. Calcd for C33H47NO5S (%): C, 69.56; H, 8.31; N, 2.46;
S, 5.63. Found (%):C, 69.54; H, 8.25; N, 2.50; S, 5.60%; X-ray: amor-
phism; HR-MS (ESI): Calcd for C33H47NO5S (M-H+):568.3102,
Found: 568.3110.
Mutilin 14-O-[1-(2-chloro)benzamide-2-methylpropane-2-yl]thio-
acetate (11b): White solid (81%); melting point: 56–58 °C; 1H NMR
spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm) = 7.67 (1H, d, J = 7.2
Hz), 7.32–7.44 (3H, m), 7.02–7.08 (1H, m), 6.40 (1H, dd, J1 = 17.2
Hz, J2 = 10.8 Hz), 5.70 (1H, d, J = 8.8 Hz), 5.18 (1H, d, J = 10.8 Hz),
5.12 (1H, d, J = 17.6 Hz), 3.51 (1H, dd, J1 = 14.0 Hz, J2 = 6.0 Hz), 3.42
(1H, dd, J1 = 14.0 Hz, J2 = 6.0 Hz ), 3.33 (1H, d, J = 6.0 Hz), 3.23 (1H,
d, J = 16.0 Hz), 3.17 (1H, d, J = 15.6 Hz), 2.28–2.32 (1H, m), 2.21–
2.26 (1H, m), 2.16–2.21 (1H, m), 2.07 (1H, s), 2.01–2.05 (1H, m),
1.74–1.78 (1H, m), 1.50–1.70 (3H, m), 1.44 (3H, s), 1.40–1.50 (2H,
m), 1.28–1.33 (1H, m), 1.37 (3H, s), 1.36 (3H, s), 1.13 (3H, s), 1.08–
1.16 (1H, m), 0.87 (3H, d, J = 6.8 Hz), 0.73 (3H, d, J = 7.2 Hz); IR
(KBr, cm−1) 3424, 3080, 2927, 2855, 1732, 1652, 1515, 1456, 1379,
1281, 1115, 751, 619, 438; Calcd for C33H46ClNO5S (%): C, 65.70; H,
7.52; N, 2.32; S, 5.32. Found: C, 65.68; H, 7.66; N, 2.44; S, 5.01%;
X-ray: amorphism; HR-MS (ESI): Calcd for C33H46ClNO5S (M-H+):
602.2712; Found 602.2705.
NMR spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm) = 8.54 (1H, d,
J = 2.8 Hz), 8.24 (2H, dd, J1 = 8.8 Hz, J2 = 2.8 Hz), 7.63 (1H, d, J =
8.8 Hz), 7.46(1H, t, J = 5.6 Hz), 6.37 (1H, dd, J1 = 18.0 Hz, J2 = 10.8
Hz), 5.72 (1H, d, J = 8.4 Hz), 5.13 (1H, d, J = 12.8 Hz), 5.12 (1H, d,
J = 16.0 Hz), 3.50 (1H, dd, J1 = 14.4 Hz, J2 = 6.4 Hz), 3.39 (1H, dd,
J1 = 14.0 Hz, J2 = 6.0 Hz), 3.34 (1H, d, J = 6.4 Hz), 3.25 (1H, d, J =
16.8 Hz), 3.17 (1H, d, J = 16.8 Hz), 2.27–2.31 (1H, m), 2.24–2.26
(1H, m), 2.14–2.23 (1H, m), 2.08 (1H, s), 2.05–2.12 (1H, m), 1.75–
1.79 (1H, m),1.49–1.68 (3 H, m), 1.45–1.49 (2H, m), 1.44 (3H, s),
1.37 (3H, s), 1.36 (3H, s), 1.15 (3H, s), 1.08-1.17 (1H, m), 0.89 (3H,
d, J = 7.2 Hz), 0.69 (3H, d, J = 7.2 Hz); IR (KBr, cm−1) 3437, 3090,
2928, 1730, 1662, 1611, 1528, 1460, 1349, 1282, 1116, 909, 741, 619,
523; Calcd for C33H45Cl N2O7S (%): C, 61.05; H, 6.99; N, 4.31; S,
4.94. Found: C, 61.00; H, 6.80; N, 4.35; S, 4.85%; X-ray: amorphism;
HR-MS (ESI): Calcd for C33H45Cl N2O7S (M-H+): 647.2563; Found
647.2567.
Mutilin 14-O-[1-(4-acetamino)benzamide-2-methylpropane-2-yl]
thioacetate (11f): Yellow solid (58%); melting point: 108–110 °C; 1H
NMR spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm) = 7.91 (2H, d,
J = 7.6 Hz), 7.63 (2H, d, J = 7.2 Hz), 7.46 (1H, m), 7.34 (1H, s), 6.42
(1H, dd, J1 = 18.0 Hz, J2 = 10.8 Hz), 5.75 (1H, d, J = 8.4 Hz), 5.14
(1H, d, J = 12.8 Hz), 5.12 (1H, d, J = 16.0 Hz), 3.51 (1H, dd, J1 = 14.0
Hz, J2 = 6.4 Hz), 3.34 (1H, d, J = 6.8 Hz), 3.20–3.25 (1H, m), 3.16–
3.29 (2H, m), 2.29–2.33 (1H, m), 2.06–2.28 (3H, m), 2.22 (3H, s),
2.09 (1H, s), 1.77–1.80 (1H, m), 1.61–1.69 (2H, m), 1.51–1.58 (1H,
m), 1.46 (3H, s), 1.43–1.48 (2H, m), 1.37–1.41 (1H, m), 1.33 (3H, s),
1.29 (3H, s), 1.15 (3H, s), 1.11–1.18 (1H, m), 0.88 (3H, d, J = 6.8 Hz),
0.73 (3H, d, J = 6.8 Hz); IR (KBr, cm−1) 3395, 3107, 2931, 2855,
1728, 1682, 1645, 1600, 1530, 1505, 1460, 1406, 1372, 1290, 1186,
1117, 1018, 981, 916, 854, 766; Calcd for C35H50 N2O6S (%): C, 67.06;
H, 8.04; N, 4.47; S, 5.12. Found: C, 69.95; H, 8.01; N, 4.50; S, 5.08%;
X-ray: amorphism; HR-MS (ESI): Calcd for C35H50 N2O6S (M-H+):
626.3390; Found 626.3383.
Mutilin 14-O-[1-(2-amino)benzamide-2-methylpropane-2-yl]thio-
acetate hydrochlorate (12c): White solid (51%); melting point:
120–123 °C; 1H NMR spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm)
= 8.35 (1H, s), 7.90–8.14 (2H, m), 7.61–7.79 (1H, m), 7.42–7.59 (1H,
m), 6.42 (1H, s), 5.74 (1H, s), 5.06–5.30 (2H, m), 3.15–3.48 (5H, m),
2.10–2.35 (5H, m), 1.60–1.84 (4H, m), 1.38–1.58 (3H, m), 1.47
(3H, s), 1.33 (6H, s), 1.17 (3H, s), 1.07–1.22 (1H, m), 0.88 (3H, s),
0.74 (3H, s); IR (KBr, cm−1) 3425, 3090, 2929, 2860, 1725, 1645,
1541, 1460, 1383, 1286, 1118, 1022, 748, 619, 442; Calcd for
C33H49ClN2O5S (%): C, 63.80; H, 7.95; N, 4.51; S, 5.16. Found: C,
63.78; H, 7.90; N, 4.62; S, 5.10%; X-ray: amorphism; HR-MS (ESI):
Calcd for C33H49ClN2O5S (M-Cl−): 585.3357; Found 585.3356.
Mutilin 14-O-[1-(4-amino)benzamide-2-methylpropane-2-yl]thio-
acetate hydrochlorate (12d): White solid (50%); melting point:
126–128 °C; 1H NMR spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm)
= 7.55–8.06 (5H, m), 6.39 (1H, s), 5.39 (1H, s), 5.05 (2H, s), 3.16–
3.54 (5H, m), 2.05–2.38 (5H, m), 1.58–1.80 (4H, m),1.35–1.50 (3H,
m), 1.42 (3H, s), 1.32 (6H, s), 1.00–1.20 (4H, m), 0.86 (3H, s), 0.70
(3H, s); IR (KBr, cm−1) 3410, 3090, 2930, 2860, 2596, 1724, 1644,
1620, 1545, 1503, 1460, 1383, 1288, 1118, 1018, 982, 848, 758, 618;
Calcd for C33H49ClN2O5S (%): C, 63.80; H, 7.95; N, 4.51; S, 5.16.
Found: C, 63.75; H, 7.88; N, 4.58; S, 5.05%; X-ray: amorphism;
HR-MS (ESI): Calcd for C33H49ClN2O5S (M-Cl−): 585.3357; Found
585.3355.
Mutilin 14-O-[1-(4-amino-2chloro)benzamide-2-methylpropane-2-
yl]thioacetate hydrochlorate (12e): White solid (55%); melting point:
126–128 °C; 1H NMR spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm)
= 7.20–8.15 (4H, m), 6.37 (1H, s), 5.70 (1H, s), 5.10–5.18 (2H, m),
3.16–3.80 (5H, m), 2.04–2.30 (5H, m), 1.58–1.80 (4H, m), 1.30–1.50
(3H, m), 1.42 (3H, s), 1.25 (6H, s), 1.20–1.50 (4H, m), 0.82–0.92 (3H,
m), 0.64–0.78 (3H, m); IR (KBr, cm−1) 3419, 3085, 2929, 2855, 2597,
1727, 1648, 1532, 1467, 1383, 1282, 1119, 822, 619; Calcd for
C33H48Cl2N2O5S (%): C, 60.45; H, 7.38; N, 4.27; S, 4.89. Found: C,
60.43; H, 7.30; N, 4.35; S, 4.80%; X-ray: amorphism; HR-MS (ESI):
Calcd for C33H48Cl2N2O5S (M-Cl−): 619.2967; Found 619.2960.
Mutilin 14-O-[1-(2-nitro)benzamide-2-methylpropane-2-yl]thio-
1
acetate (11c): Buff solid (95%); melting point: 68–69 °C; H NMR
spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm) = 8.05 (1H, d, J = 7.6
Hz), 7.58–7.71 (3H, m), 7.19 (1H, t, J = 5.2 Hz), 6.36 (1H, dd, J1 =
17.6 Hz, J2 = 11.2 Hz), 5.67 (1H, d, J = 8.8 Hz), 5.14 (1H, d, J = 10.4
Hz), 5.13 (1H, d, J = 17.2 Hz), 3.33–3.48 (2H, m), 3.34 (1H, d, J = 6.4
Hz), 3.25 (1H, d, J = 16.4 Hz), 3.17 (1H, d, J = 16.4 Hz), 2.28–2.31
(1H, m), 2.21–2.26 (1H, m), 2.16–2.21 (1H, m), 2.08 (1H, s),
2.04–2.10 (1H, m), 1.75–1.78 (1H, m), 1.53–1.70 (3H, m), 1.43–1.51
(2H, m), 1.43 (3H, s), 1.29–1.31 (1H, m), 1.38 (3H, s), 1.37 (3H, s),
1.14 (3H, s), 1.08–1.17 (1H, m), 0.89 (3H, d, J = 6.4 Hz), 0.69 (3H, d,
J = 7.2 Hz); IR (KBr, cm−1) 3430, 3080, 2927, 2860, 1729, 1658,
1533, 1458, 1351, 1282, 1115, 699, 619, 438; Calcd for C33H46N2O7S
(%): C, 64.47; H, 7.54; N, 4.56; S, 5.22. Found: C, 64.26; H, 7.50;
N, 4.57; S, 5.22%; X-ray: amorphism; HR-MS (ESI): Calcd for
C33H46N2O7S (M-H+): 613.2943; Found 613.2940.
Mutilin 14-O-[1-(4-nitro)benzamide-2-methylpropane-2-yl]thio-
1
acetate (11d): Buff solid (80%); melting point:70–72 °C; H NMR
spectrum (400 MHz; d1-CDCl3; TMS): δ (ppm) = 8.33 (2H, d, J = 8.4
Hz), 8.12 (2H, d, J = 8.8 Hz), 7.85 (1H, d, J = 5.6 Hz), 6.39 (1H, dd,
J1 = 17.2 Hz, J2 = 10.8 Hz), 5.73 (1H, d, J = 8.4 Hz), 5.13 (1H, d,
J = 17.2 Hz), 5.05 (1H, d, J = 10.8 Hz), 3.52 (1H, dd, J1 = 14.0 Hz,
J2 = 6.4 Hz), 3.35 (1H, d, J = 8.8 Hz), 3.31 (1H, d, J = 16.8 Hz),
3.22–3.28 (1H, m), 3.20 (1H, d, J = 17.6 Hz), 2.08–2.31 (4H, m ), 2.10
(1H, s), 1.76–1.80 (1H, m), 1.61–1.72 (2H, m), 1.50–1.54 (1H, m),
1.43–1.51 (2H, m), 1.47 (3H, s), 1.36–1.41 (1H, m), 1.34 (3H, s), 1.31
(3H, s), 1.16 (3H, s), 1.11–1.18 (1H, m), 0.88 (3H, d, J = 6.8 Hz), 0.72
(3H, d, J = 7.2 Hz); IR (KBr, cm−1) 3430, 2925, 1725, 1644, 1610,