Study on the structure-activity relations of pleuromutilin derivatives with an aromatic amide and a thioether group in the C14 side chain

Article abstract of DOI:10.3184/030823410X12744531851242

Nine novel pleuromutilin derivatives having benzamide substituents have been synthesised permitting structureactivity relations of pleuromutilin derivatives with aromatic amide and thioether groups in the C₁₄ side chain to be studied. The results showed that the heterocyclic carboxamide group was necessary to enhance bio-activities.

Full text of DOI:10.3184/030823410X12744531851242

354 RESEARCH PAPER
JUNE, 354–357
JOURNAL OF CHEMICAL RESEARCH 2010
Study on the structure-activity relations of pleuromutilin derivatives with
an aromatic amide and a thioether group in the C14 side chain
Ke-ping Xua, Yuan-yuan Zhangb, Juan Luoa, Shan-li Chena and Yu-liang Wanga*
aCollege of Chemistry, Sichuan University, Chengdu, Sichuan 610064, P. R. China
bDepartment of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
Nine novel pleuromutilin derivatives having benzamide substituents have been synthesised permitting structure-
activity relations of pleuromutilin derivatives with aromatic amide and thioether groups in the C14 side chain to be
studied. The results showed that the heterocyclic carboxamide group was necessary to enhance bio-activities.
Keywords: benzamide, pleuromutilin, structure–activity, antibacterial activities
The antibiotic Pleuromutilin 1 was first isolated in 19511 with
moderate bioactivity against drug-resistant Gram-positive bac-
teria and mycoplasmas in vitro.2,3 Earlier research reported4–6
that modifications of the side chain at C14 including both a
thioether group and a basic group offered the most possibilities
for achieving the best bioactivities. On this basis, Tiamulin 26,7
was synthesised with excellent bioactivity against Gram-
positive bacteria and mycoplasmas. Further researches led
to the development of Valnemulin 38 with much better bio-
activity than Tiamulin, which was the best pleuromutilin
antibiotic for use in animals.9 In the 1980s, Azamulin 410 was
discovered with good bio-activity, but it has limited solubility
in water.11 Later, Retapamulin 512 with excellent bioactivity
was produced as the first pleuromutilin antibiotic for potential
use in humans.13,14 Recently, 6 and related compounds having
excellent bioactivity and good solubility in water were
synthesised (Fig. 1).11,15,16
Some potent antibacterial derivatives with heterocyclic
carboxamide groups in the C14 side chain were designed and
synthesised in our previous work17. In this series, 7 and related
compounds displayed excellent bioactivities against Gram-
positive bacteria in vitro. This is a very interesting result.
So we focused our attention on a functional group, the hetero-
cyclic carboxamide group. In order to find out whether the
heterocyclic carboxamide group is necessary to enhance
bio-activities, nine novel pleuromutilin derivatives 11a–f and
12c–e with benzamide substituents in place of the heterocyclic
carboxamide have been synthesised and their structure-activity
relations were studied. The synthetic route is shown in
Scheme 1.
Experimental
Melting points were determined with XRC-1 melting point apparatus
(Sichuan University Instrument Inc., Chengdu, China) without being
1
corrected. H NMR spectra were run on a Varian INOVA-400 spec-
trometer (Varian Inc., Palo Alto, CA, USA) with CDCl3 as the solvent
and TMS as the internal standard. Mass spectra were recorded with
Agilent 6210 (DOF-MAS) spectrometer (Agilent Inc., Santa Clara,
CA, USA) using the EI method. IR spectra were recorded with Perkin-
Elmer 16PC-FT instrument (Perkin-Elmer Inc., Norwalk Conn, CA,
USA). Elemental analyses were carried out by the Euro EA 3000
instrument (EuroVector S.P.A., Italy). X-ray diffraction were recorded
with Philips X-ray Diffraction apparatus (X’Pert Pro MPD Dy1291).
8: p-Methylbenzenesulfonyl chloride (1.91 g, 0.010 mol) in 1,2-
dichloroethane (10 mL) was slowly added to a mixture of pleuro-
mutilin (3.54 g, 0.0094 mol), triethylamine (1.20 g, 0.012 mol) and
pyridine (three drops) in 1,2-dichloroethane (10 mL). The mixture
was stirred at 10–15 °C for 20h, washed with water (3 × 10 mL),
then concentrated almost to dryness. Purification was achieved by
Fig. 1 Structure of pleuromutilin derivatives.
* Correspondent. E-mail: chemwang2000@163.com

JOURNAL OF CHEMICAL RESEARCH 2010 355
Scheme 1 The synthetic route of compounds 11a–f and 12c–e.
recrystallisation from 85% ethyl alcohol to afford a white solid 3.90g
(yield 78%).
The mixture was stirred at room temperature for 2h, concentrated and
then ethyl acetate (20 mL) was added. The organic phase was washed
with water (3 × 10 mL) and then 2N HCl (3 × 10 mL), dried with
sodium sulfate and evaporated in vacuo to give the crude product. The
crude product was chromatographed on silica gel using petroleum
ether/ethyl acetate (1:1) as eluent to afford a white solid 0.26 g (yield
50%).
9: Sodium (1.71 g, 0.074 mol) was added portionwise to absolute
ethanol (150 mL). The mixture was stirred at room temperature until
the sodium was dissolved completely. 1-Amino-2-methyl-2-propane-
thiol hydrochloride (5.00 g, 0.035 mol) and compound 8 (17.10 g,
0.032 mol) were added to the mixture. The mixture was stirred for 1h
at room temperature, poured into ice water (200 mL) and extracted
with ethyl acetate (3 × 100 mL). The ethyl acetate extract was washed
with water, extracted with dilute hydrochloric acid (12 × 20 mL,
0.0001 mol L−1). The aqueous layer was made alkaline and extracted
with ethyl acetate which had only one product as checked by TLC.
Then the combined organic phases were washed with water (3 ×
10 mL), dried over sodium sulfate and evaporated in vacuum to afford
a white solid 13.39 g (yield 90%).
Preparation of 11b–e; general procedure
10b–e (1.5 mmol) in thionyl chloride (3 mL) was refluxed for 3h. The
excess thionyl chloride was evaporated in vacuo and the residue was
cooled to 0 °C. Dichloromethane (10 mL), triethylamine (3.0 mmol)
and 14-O-[(1-amino-2-methylpropane-2-yl)thioacetyl-]mutilin (1.2
mmol) in dichloromethane (5 mL) were added in turn. The mixture
was stirred at room temperature for 1–2h, evaporated and ethyl acetate
(20 mL) was added. The organic phase was washed with water (3 ×
10 mL), 2N HCl (3 × 10 mL) and saturated brine (10 mL), dried
with sodium sulfate and evaporated in vacuo to afford solid (yield
80–95%).
11f: 10f (0.27 g, 1.5 mmol) in thionyl chloride (5 mL) was heated
at 45 °C for 1h. The excess thionyl chloride was evaporated in vacuo
and the residue was cooled to 0 °C. Dichloromethane (10 mL), trieth-
ylamine (0.61 g, 6.0 mmol) and 14-O-[(1-amino-2-methyl-propane-2-
yl)thioacetyl-]mutilin (0.46 g, 1.0 mmol) in dichloromethane (5 mL)
were added in turn. The mixture was stirred at room temperature for
2.5h, concentrated and ethyl acetate (20 mL) was added. The organic
phase was washed with water (3 × 10 mL), 2N HCl (3 × 10 mL) and
10e: Synthesised by a literature18 procedure.
10f: 4-Aminobenzoic acid (0.28 g, 0.002 mol) was added to acetic
anhydride. The mixture was heated to 130 °C and kept at this tem-
perature for 3h, cooled to room temperature and neutralised with 30%
sodium hydroxide to pH 7. The mixture was filtered, and the subse-
quent wet cake was washed with water and dried to afford a white
solid 0.28g (yield 78%).
11a: Benzoic acid (0.12g, 1.0 mmol) in thionyl chloride (2.5 mL)
was refluxed for 3h. The excess thionyl chloride was evaporated
in vacuo and the residue was cooled to 0 °C. Dichloromethane (8 mL),
triethylamine (0.40 g, 4.0 mmol) and 14-O-[(1-amino-2-methylpro-
pane-2-yl)thioacetyl-]mutilin (0.42 g, 0.9 mmol) were added in turn.

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,

JOURNAL OF CHEMICAL RESEARCH 2010 357
Table 1 The antibacterial activities of 0.1 g L−1 target com-
pounds against three bacterial strains
pleuromutilin derivatives with heterocyclic carboxamide and
thioether groups in the C14 side chain.
Compound
Diameter of bacteriostatic circle/mm
We thank for the financial support from the National Science
Foundation of China (Nos. 20372052) and H NMR analysis
E. coli
S. lignieres
S. aureus
1
11a
16.3
15.4
17.2
15.4
15.3
17.1
16.0
16.2
15.9
18.9
14.9
13.4
12.6
14.2
14.1
13.8
14.2
14.7
14.4
14.1
13.6
13.3
15.4
16.9
16.8
15.7
15.8
18.2
15.2
17.6
15.4
21.9
17.4
by Sichuan University Analytical & Testing Center.
11b
11c
Received 28 March 2010; accepted 10 May 2010
Paper 1000031 doi: 10.3184/030823410X12744531851242
Published online: 2 July 2010
11d
11e
11f
12c
12d
References
12e
1
2
3
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Blank
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4
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The antibacterial activities of the target compounds were tested
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resulting solution was added to the flat plate of an Oxford cup which
was covered with culture and kept at 37 °C for 24h. The results of
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Discussion
The bioactivities of compounds 11a–f and 12c–e against
E. coli, S. lignieres, and S. aureus are shown in Table 1.
The results show that all of the new derivatives in which the
heterocyclic carboxamide group was replaced by a benzamide
group were inactive. This proved that the heterocyclic car-
boxamide group was essential to enhance bioactivities. Based
on this conclusion, we will continue further to study novel
18 Y.M. Zheng and X.R. Jin, HeiLongJiang Med. J., 1999, 12, 204.

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