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Z. Cui et al. / Bioorg. Med. Chem. Lett. 21 (2011) 7193–7196
The filtrate was concentrated in vacuo to furnish 3 as white solid. Compound 3
(10.0 mmol) was suspended into 50 mL methanol and reacted with 98%
hydrazine monohydrate (200 mmol, 9.7 mL) under reflux for 12 h. The white
1297.86, 1033.66 cmꢀ1 1H NMR (400 MHz, CD3OD+D2O):
. d 3.17 (t, 1H,
J = 9.2 Hz, H-4), 3.26-3.31 (m, 2H, Glc-H), 3.38 (t, 1H, J = 8.6 Hz, H-5), 3.67
(dd, 1H, J = 12.2 Hz, 5.4 Hz, H-6proR), 3.86 (dd, 1H, J = 12.0 Hz, 2.0 Hz, H-6proS),
4.57 (d, 1H, J = 9.6 Hz, Glc-anomeric H), 7.09 (d, 1H, J = 4.0 Hz, FuH), 7.31 (d, 1H,
J = 3.6 Hz, FuH), 7.33 (dd, 1H, J = 7.8 Hz, 1.8 Hz, PhH-Fu), 7.40–7.54 (m,
4H, 2PhH-S+2PhH-Fu), 7.60 (dd, 1H, J = 7.6 Hz, 1.6 Hz, PhH-S), 7. 89 (dd,
1H, J = 7.6 Hz, 1.2 Hz, PhH-S), 8.14 (dd, 1H, J = 7.8 Hz, 1.8 Hz, PhH-Fu), 8.19 (s,
1H, CH@N). ESI-MS: m/e 541 [M+Na]+ (Pos), 517 [M-H]ꢀ (Neg). ESI-HRMS
Calcd. for C24H23ClN2O7S: [M+H]+ 519.0914. Found: 519.0936.
solid was filtered, washed with methanol and dried to afford compound 4.
2-thio-b-
193–194 °C.
D
-glucopyranosyl benzohydrazide (4a). White solid: yield 97%. mp
ꢀ66.0° (c 1.0, water). IR (KBr): mmax 3861.75, 3742.19,
½ ꢁ
a 2D5
1644.98, 1549.52, 1531.20, 1515.77, 1464.67, 1367.28, 1256.40, 1047.16 cmꢀ1
.
1H NMR (400 MHz, D2O): d 3.23–3.45 (m, 4H, Glc-H), 3.63 (dd, 1H, J = 12.4 Hz,
5.6 Hz, H-6proR), 3.82 (dd, 1H, J = 12.2 Hz, 2.4 Hz, H-6proS), 4.66 (d, 1H,
J = 10.0 Hz, Glc-anomeric H), 7.37–7.41 (m, 2H, PhH), 7.45–7.49 (m, 1H, PhH),
7.69 (d, 1H, J = 8.0 Hz, PhH). ESI-MS: m/e 353 [M+Na]+ (Pos), 329 [M-H]ꢀ (Neg).
Anal. Calcd. (%) for C13H18N2O6S: C, 47.26; H, 5.49; N, 8.48. Found: C, 47.58; H,
5.26; N, 8.74.
50-(2-chlorophenyl)furan-20-carbaldehyde-2-b-
D
-glucopyranosyl
benzoyl
+1.6° (c
hydrazone (5e). Light brown solid: yield 97%. mp 151–152 °C. ½a D25
ꢁ
1.0, MeOH). IR (KBr): mmax 3392.17, 1644.98, 1549.52, 1462.74, 1304.61,
1240.00, 1081.87, 899.63, 755.96 cmꢀ1 1H NMR (400 MHz, CD3OD+D2O): d
.
2-b-
D
-glucopyranosyl benzohydrazide (4b). White solid: yield 92%. mp 220–
3.45 (t, 1H, J = 9.0 Hz, H-4), 3.51–3.64 (m, 3H, Glc-H), 3.77 (dd, 1H, J = 12.0 Hz,
5.6 Hz, H-6proR), 3.95 (dd, 1H, J = 12.0 Hz, 2.0 Hz, H-6proS), 5.05 (d, 1H, J = 8.0 Hz,
Glc-anomeric H), 7.09 (d, 1H, J = 4.0 Hz, FuH), 7.21–7.25 (m, 1H, PhH-O), 7.31
(d, 1H, J = 3.6 Hz, FuH), 7.33 (dd, 1H, J = 8.0 Hz, 1.6 Hz, PhH-Fu), 7.42 (td, 1H,
J = 7.7 Hz, 1.3 Hz, PhH-Fu), 7.47–7.50 (m, 2H, PhH-Fu+PhH-O), 7.54–7.58 (m,
1H, PhH-O), 7. 97 (dd, 1H, J = 7.8 Hz, 1.8 Hz, PhH-O), 8.16 (dd, 1H, J = 8.0 Hz,
1.6 Hz, PhH-Fu), 8.34 (s, 1H, CH=N). ESI-MS: m/e 503 [M+H]+ (Pos), 501 [M-H]ꢀ
(Neg). ESI-HRMS Calcd. for C24H23ClN2O8: [M+H]+ 503.1143. Found: 503.1124.
221 °C. ½a 2D5
ꢁ
ꢀ56.0° (c 0.5, water). IR (KBr): mmax 3742.19, 3380.60, 1646.91,
1531.20, 1312.32, 1226.50, 1078.01, 1034.62, 749.21 cmꢀ1
.
1H NMR (300 MHz,
DMSO-d6+D2O): d 3.15–3.22 (m, 1H, Glc-H), 3.29–3.43 (m, 3H, Glc-H), 3.48 (dd,
1H, J = 11.8 Hz, 5.9 Hz, H-6proR), 3.73 (dd, 1H, J = 11.7 Hz, 1.7 Hz, H-6proS), 4.94
(dd, 1H, J = 5.5 Hz, 2.2 Hz, Glc-anomeric H), 7.13–7.18 (m, 1H, PhH), 7.32–7.35
(m, 1H, PhH), 7.45–7.51 (m, 1H, PhH), 7.75 (dd, 1H, J = 7.7 Hz, 2.2 Hz, PhH). ESI-
MS: m/e 314.9 [M+H]+, 336.9 [M+Na]+(Pos). Anal. Calcd. (%) for C13H18N2O7: C,
49.68; H, 5.77; N, 8.91. Found: C, 50.03; H, 5.86; N, 8.64.
2-thio-b-
180–181 °C.
1532.17, 1464.67, 1366.32, 1086.69, 979.66 cmꢀ1
50-(2,4-di-fluorophenyl)furan-20-carbaldehyde-2-thio-b-
D-lactosyl
benzoyl
D
-galactopyranosyl benzohydrazide (4c). White solid: yield 97%. mp
ꢀ52.0° (c 1.0, water). IR (KBr): mmax 3235.00, 1612.20.
1H NMR (400 MHz, D2O): d
hydrazone (5f). Yellow solid: yield 80%. mp 180–181 °C. ½a D25
ꢁ
+20.5° (c 1.0,
½
a 2D5
ꢁ
MeOH). IR (KBr): mmax 3391.50, 2882.61, 1639.69, 1560.03, 1517.41, 1487.85,
.
1431.82, 1384.38, 1270.55, 1144.15 cmꢀ1 1H NMR (400 MHz, CD3OD+D2O): d
.
3.52–3.73 (m, 5H, Gal-H), 3.91 (d, 1H, J = 3.2 Hz, H-4), 4.64 (d, 1H, J = 9.2 Hz,
Gal-anomeric H), 7.35–7.41 (m, 2H, PhH), 7.47 (dt, 1H, J = 7.4 Hz, 2.4 Hz, PhH),
7.69 (d, 1H, J = 8.0 Hz , PhH). ESI-MS: m/e 353 [M+Na]+ (Pos), 329 [M-H]ꢀ (Neg).
Anal. Calcd. (%) for C13H18N2O6S: C, 47.26; H, 5.49; N, 8.48. Found: C, 47.02; H,
5.67; N, 8.73.
3.51–3.76 (m, 10H, Lac-H), 3.86–3.94 (m, 2H, Lac-H), 3.39 (d, 1H, J = 7.5 Hz,
GalH-1), 4.71 (d, 1H, J = 9.6 Hz, GlcH-1), 7.00 (t, 1H, J = 3.6 Hz, FuH), 7.10 (d, 1H,
J = 3.6 Hz, FuH), 7.16–7.20 (m, 1H, PhH), 7.46–7.61 (m, 4H, PhH), 7.74–7.79 (m,
2H, PhH), 8.18 (s, 1H, CH@N). ESI-MS: m/e 683.1 [M+H]+, 705.1 [M+Na]+ (Pos).
ESI-HRMS Calcd. for C30H32F2N2O12S: [M+H+] 683.1644. Found: 683.1636.
2-thio-b-
D
-lactosyl benzohydrazide (4d). White solid: yield 92%. mp 236–
ꢀ34.0° (c 1.0, water). IR (KBr): mmax 3439.47, 3321.56, 2952.35,
50-(2-chlorophenyl)furan-20-carbaldehyde-2-thio-b-
D-lactosyl
benzoyl
237 °C. ½a 2D5
ꢁ
hydrazone (5g). Yellow solid: yield 83%. mp 222–223 °C. ½a D25
ꢁ
+22.0° (c 0.25,
2912.77, 2864.98, 1672.52, 1596.00, 1513.32, 1465.07, 1434.87, 1114.84,
MeOH). IR (KBr): mmax 3369.09, 2927.73, 2877.47, 1649.91, 1549.07, 1507.71,
1083.30 cmꢀ1
.
1H NMR (300 MHz, D2O): d 3.29–3.34 (m, 1H, Lac-H), 3.44–3.76
1468.63, 1303.54, 1120.16, 1075.05 cmꢀ1 1H NMR (400 MHz, CD3OD+D2O): d
.
(m, 10H, Lac-H), 3.86–3.91 (m, 2H, Lac-H), 4.37 (dd, 1H, J = 7.7 Hz, 1.9 Hz, Glc-
anomeric H), 7.41–7.50 (m, 3H, PhH), 7.68–7.71 (m, 1H, PhH). ESI-MS: m/e
493.1 [M+H]+, 515.1 [M+Na]+(Pos). Anal. Calcd. (%) for C19H28N2O11S: C, 46.34;
H, 5.73; N, 5.69. C, 45.97; H, 5.51; N, 5.92.
3.51–3.75 (m, 10H, Lac-H), 3.86–3.92 (m, 2H, Lac-H), 3.39 (d, 1H, J = 7.5 Hz,
GalH-1), 4.71 (d, 1H, J = 9.8 Hz, GlcH-1), 7.11 (d, 1H, J = 3.8 Hz, FuH), 7.33 (d,
1H, J = 3.8 Hz, FuH), 7.46–7.61 (m, 6H, PhH), 7.79–7.82 (m, 1H, PhH), 8.05–8.08
(m, 1H, PhH), 8.18 (s, 1H, CH@N). ESI-MS: m/e 681.1 [M+H]+, 703.0 [M+Na]+
(Pos). ESI-HRMS Calcd. for C30H33ClN2O12S: [M+H]+ 681.1443. Found:
681.1461.
16. Preparation of compounds 5a–5g:
A mixture of aldehyde (0.05 mol) and
acylhydrazine (0.05 mol) reacted in ethanol under reflux for 5 h. After
4
cooling, the solvent was removed under reduced pressure, and the residue was
purified by column chromatography on silica gel using chloroform and
methanol as the eluent to yield the title compounds 5a–5g.
17. Anticancer activity was screened against three different cell lines: a human
hepatocellular carcinoma cell line (Bel-7402), a human gastric carcinoma cell
line (BGC-823), and a human nasopharyngeal carcinoma cell line (KB). All the
experiments were performed on exponentially growing cancer cells. Bel-7402,
BGC-823 and KB cells were assayed by SRB. The absorbance of each well was
measured using a microculture plate reader at 540 nm.
18. (a) Tietze, L. F.; Schuster, H. J.; Krewer, B.; Schuberth, I. J. Med. Chem. 2009, 52,
537; (b) de Graaf, M.; Pinedo, H. M.; Quadir, R.; Haisma, H. J.; Boven, E. Biochem.
Pharmacol. 2003, 65, 1875; (c) Leu, Y. L.; Chen, C. S.; Wu, Y. J.; Chern, J. W. J.
Med. Chem. 2008, 51, 1740.
50-(2,4-di-fluorophenyl)furan-20-carbaldehyde-2-thio-b-
D-glucopyranosylben-
zoyl hydrazone (5a). Light yellow solid: yield 76%. mp 160–161 °C. ½a D25
+7.8° (c
ꢁ
1.0, MeOH). IR (KBr): mmax 3742.19, 3450.99, 1644.98, 1550.49, 1482.99,
1427.07, 1304.61, 1271.82, 1050.05, 976.77 cmꢀ1
CD3OD+D2O): d 3.14–3.40 (m, 4H, Glc-H), 3.67 (dd, 1H, J = 12.2 Hz, 5.8 Hz, H-
proR), 3.86 (dd, 1H, J = 12.0 Hz, 2.0 Hz, H-6proS), 4.57 (d, 1H, J = 9.6 Hz, Glc-
.
1H NMR (400 MHz,
6
anomeric H), 6.94 (t, 1H, J = 3.4 Hz, FuH), 7.06 (d, 1H, J = 3.6 Hz, FuH), 7.09–7.13
(m, 2H, PhH-Fu), 7.45–7.54 (m, 2H, PhH-S), 7.60 (dd, 1H, J = 7.4 Hz, 1.8 Hz,
PhH-S), 7. 90 (dd, 1H, J = 7.6 Hz, 1.2 Hz, PhH-S), 8.13–8.19 (m, 2H, PhH-
Fu+CH@N). ESI-MS: m/e 543 [M+Na]+ (Pos), 519 [M-H]ꢀ (Neg). ESI-HRMS
Calcd. for C24H22F2N2O7S: [M+H]+ 521.1116. Found: 521.1122.
19. (a) Hafez, H. N.; Hussein, H. A. R.; El-Gazzar, A. R. B. A. Eur. J. Med. Chem. 2010,
45, 4026; (b) Hirohara, S.; Obata, M.; Alitomo, H.; Sharyo, K.; Ando, T.; Tanihara,
M.; Yano, S. J. Photochem. Photobiol., B 2009, 97, 22.
20. Fungicidal activities of the title compounds against Phytophthora capsici,
Fusarium oxysporum, Corynespora cassiicola, and Rhizoctonia solanii were
evaluated using pot culture test according to Ref. 21. The fungal stains of
P. capsici, F. oxysporum, C. cassiicola, and R. solanii were provided by Institute of
Vegetables and Flowers, Chinese Academy of Agricultural Science, Beijing,
China. P. capsici was maintained on oat medium at 17 °C, F. oxysporum, C.
cassiicola, and R. solanii were maintained on potato dextrose agar (PDA)
mediumat at 4 °C. The culture plates were cultivated at 24 1 °C. Four
commercial fungicides: procymidone, thiophanate-methyl, chlorothalonil,
and validamycin were evaluated as controls against mentioned above four
fungi at the same condition. The relative inhibition rate of the circle mycelium
compared to blank assay was calculated via the following equation:
50-(2,4-di-fluorophenyl)furan-20-carbaldehyde-2-b-
D-glucopyranosyl benzoyl
hydrazone (5b). Yellow solid: yield 97%. mp 166–167 °C. ½a D25
+3.0° (c 1.0,
ꢁ
MeOH). IR (KBr): mmax 3291.89, 2883.06, 1625.70, 1551.45, 1483.96, 1237.11,
1073.19, 906.38, 797.42 cmꢀ1 1H NMR (400 MHz, CD3OD+D2O): d 3.45 (t, 1H,
.
J = 9.2 Hz, H-4), 3.51–3.56 (m, 2H, Glc-H), 3.59–3.63 (m, 1H, H-5), 3.77 (dd, 1H,
J = 12.0 Hz, 5.6 Hz, H-6proR), 3.95 (dd, 1H, J = 12.0 Hz, 2.0 Hz, H-6proS), 5.05 (d,
1H, J = 8.0 Hz, Glc-anomeric H), 6.93 (t, 1H, J = 3.6 Hz, FuH), 7.06 (d, 1H,
J = 3.6 Hz, FuH), 7.07–7.10 (m, 2H, PhH-Fu), 7.21–7.25 (m, 1H, PhH-O), 7.49 (dd,
1H, J = 8.2 Hz, 1.0 Hz, PhH-O), 7.54–7.58 (m, 1H, PhH-O), 7. 97 (dd, 1H,
J = 7.8 Hz, 1.8 Hz, PhH-O), 8.14–8.20 (m, 1H, PhH-Fu), 8.32 (s, 1H, CH@N). ESI-
MS: m/e 505 [M+H]+ (Pos), 503 [M-H]ꢀ (Neg). ESI-HRMS Calcd. for
C
24H22F2N2O8: [M+H]+ 505.1344. Found: 505.1359.
50-(2,4-di-fluorophenyl)furan-20-carbaldehyde-2-thio-b-
D-galactopyranosyl
0
dex ꢀ dex
Relati
v
einhibitionrateð%Þ ¼
ꢂ 100%
benzoyl hydrazone (5c). Brown solid: yield 71%. mp 144–146 °C. ½a D25
+1.8° (c
ꢁ
dex
1.0, MeOH). IR (KBr): mmax 3411.46, 1644.98, 1550.49, 1482.99, 1427.07,
1269.90, 1141.65, 1056.80, 966.16, 857.20, 801.28 cmꢀ1 1H NMR (400 MHz,
.
Where dex is the extended diameter of the circle mycelium during the blank as-
say; and d0ex is the extended diameter of the circle mycelium during testing.
21. (a) Shi, Y. X.; Yuan, L. P.; Zhang, Y. B.; Li, B. J. Nongyaoxue Xuebao 2007, 9, 126;
(b) Liu, X. H.; Shi, Y. X.; Ma, Y.; Zhang, C. Y.; Dong, W. L.; Pan, L.; Wang, B. L.; Li,
B. J.; Li, Z. M. Eur. J. Med. Chem. 2009, 44, 2782; (c) Liu, X. H.; Shi, Y. X.; Ma, Y.;
He, G. R.; Dong, W. L.; Zhang, C. Y.; Wang, B. L.; Wang, S. H.; Li, B. J.; Li, Z. M.
Chem. Biol. Drug Des. 2009, 73, 320; (d) Wang, B. L.; Shi, Y. X.; Ma, Y.; Liu, X. H.;
Li, Y. H.; Song, H. B.; Li, B. J.; Li, Z. M. J. Agric. Food Chem. 2010, 58, 5515.
22. (a) Liao, Q.; Yao, J. H.; Li, F.; Yuan, S. G.; Doucet, J. P.; Panaye, A.; Fan, B. T. SAR
QSAR Environ. Res. 2004, 15, 217; (b) Liao, Q.; Yao, J. H.; Yuan, S. G. Mol. Div.
2007, 11, 59; (c) Liu, B.; Yu, F.; Yao, J. H.; Liao, Q.; Fan, B. T. Nongyaoxue Xuebao
2007, 9, 220.
CD3OD+D2O): d 3.51 (dd, 1H, J = 9.2 Hz, 3.2 Hz, H-3), 3.56–3.59 (m, 1H, H-5),
3.61 (d, 1H, J = 9.2 Hz, H-2), 3.69 (dd, 1H, J = 11.6 Hz, 4.8 Hz, H-6proS), 3.78 (dd,
1H, J = 11.6 Hz, 7.2 Hz, H-6proR), 3.88 (d, 1H, J = 2.4 Hz, H-4), 4.59 (d, 1H,
J = 9.6 Hz, Gal-anomeric H), 6.93 (t, 1H, J = 3.2 Hz, FuH), 7.06 (d, 1H, J = 3.6 Hz,
FuH), 7.08–7.13 (m, 2H, PhH-Fu), 7.43–7.53 (m, 2H, PhH-S), 7.59 (dd, 1H,
J = 7.2 Hz, 1.6 Hz, PhH-S), 7. 90 (dd, 1H, J = 8.0 Hz, 0.8 Hz, PhH-S), 8.13–8.19 (m,
1H, PhH-Fu), 8.21 (s, 1H, CH@N). ESI-MS: m/e 543 [M+Na]+ (Pos), 519 [M-H]ꢀ
(Neg). ESI-HRMS Calcd. for C24H22F2N2O7S: [M+H]+ 521.1116. Found: 521.1102.
50-(2-chlorophenyl)furan-20-carbaldehyde-2-thio-b-
D-glucopyranosyl benzoyl
hydrazone (5d). Yellow solid: yield 69%. mp 139–140 °C. ½a D25
+5.6° (c 1.0,
ꢁ
MeOH). IR (KBr): mmax 3742.19, 3423.99, 1644.98, 1549.52, 1464.47, 1428.03,