3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑的合成及抗菌活性

doi:10.7503/cjcu20150194

摘要/Abstract

摘要：

以自制的5-取代芳基-4-氨基-3-巯基-1,2,4三唑为底物, 经糖基修饰后, 在甲醇钠/甲醇/二氯甲烷体系中经水解脱除糖环上的乙酰基, 得到9个新化合物5-取代苯基-4-氨基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(6a~6i), 其结构经核磁共振波谱(¹H NMR,¹³C NMR), 红外光谱(IR)和高分辨质谱(HRMS)确认. 生物活性测试结果表明, 目标化合物对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念珠菌均显示出良好的抑菌活性. 化合物6g对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念珠菌的最小抑菌浓度分别达到2, 8, 32和8 μg/mL, 抑菌效果接近或优于对照药物三氯生和氟康唑. 利用Autodock程序研究了目标化合物(6a~6i)与大肠杆菌烯脂酰还原酶(FabⅠ)受体蛋白分子的相互作用和结合自由能变化规律.

关键词: 1,2,4-三唑, S-β-D-糖苷, 去乙酰化, 抗菌活性, 烯脂酰还原酶

Abstract:

Nine novel compounds of 5-substituted-phenyl-4-amino-3-S-(β-D-glucopyranosyl)-1,2,4-triazole(6a—6i) were synthesized from 5-substituted phenyl-4-amino-3-ylsulfanyl-4H-1,2,4-triazol by glycosylation and then by deacetylate in the system of sodium methylate, methanol and dichloromethane. Their structures were confirmed by ¹H NMR, ¹³C NMR, IR and HRMS spectroscopy. The results of preliminary bioassay showed that most of the tested compounds display variable inhibitory activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Monilia albican. Especially, the compound 6g had the strongest antibacterial activity with minimum inhibitory concentration of 2, 8, 32, 8 μg/mL against the four tested strains respectively which are similar to or higher than those of the controlled drug fluconazole or triclosan. The interaction and binding free energy of compounds 6a—6i with FabⅠ were studied by Autodock.

Key words: 1,2,4-Triazole, S-β-D-Glucoside, Deacetylation, Antibacterial activity, FabⅠ

中图分类号:

O626.26

TrendMD:

张瑞波, 卢俊瑞, 刘金彪, 穆江蓓, 杨旭云, 王宏韫, 王美君, 张贺, 张玫. 3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑的合成及抗菌活性. 高等学校化学学报, 2015, 36(8): 1521.

ZHANG Ruibo, LU Junrui, LIU Jinbiao, MU Jiangbei, YANG Xuyun, WANG Hongyun, WANG Meijun, ZHANG He, ZHANG Mei. Synthesis and Antibacterial Activities of 3-S-(β-D-Glucosides)-1,2,4-triazole^†. Chem. J. Chinese Universities, 2015, 36(8): 1521.

图/表 9

Scheme 1 Syntheses of the target compounds 6a—6i

Table 1 Appearance, yields, melting points, ESI-TOF-MS and IR data for target compounds 5a—5d, 5f—5i and 6a—6i

Compd.	Appearance	Yield(%)	m.p./℃	ESI-TOF-MS ([M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
5a	White solid	67	76—78	539.1459	3449, 3225, 2961, 1754, 1624, 1586, 1484, 1373, 1227, 1039, 758
5b	White solid	68	178—179	539.1461	3442, 3230, 1751, 1614, 1467, 1401, 1223, 1045, 848
5c	Yellow solid	65	79—80	523.1498	3424, 2958, 1753, 1630, 1549, 1468, 1372, 1226, 1040, 913, 773, 696
5d	White solid	64	84—86	537.1672	3449, 2963, 1751, 1624, 1502, 1435, 1378, 1226, 1041, 824
5f	Yellow solid	63	67—68	557.1107	3446, 2961, 1752, 1635, 1441, 1376, 1226, 1046, 767
5g	Yellow solid	65	153—154	601.0608	3450, 1751, 1635, 1454, 1382, 1226, 1094, 828
5h	Yellow solid	65	122—124	538.1601	3380, 3231, 2959, 1758, 1612, 1471, 1373, 1228, 1040, 838
5i	Yellow solid	67	174—175	537.1641	3448, 2958, 1746, 1637, 1437, 1376, 1241, 1098, 1060, 795
6a	Yellow solid	76	96—97	371.1016	3475, 3417, 1626, 1422, 1129, 773
6b	Yellow solid	74	119—121	371.1017	3416, 2921, 2862, 1620, 1463, 1276, 1172, 1054, 830
6c	Brown solid	82	132—133	355.1075	3471, 3415, 2925, 2861, 1628, 1460, 1273, 1120, 1051, 770, 688
6d	White solid	75	126—127	369.1228	3414, 2920, 1629, 1464, 1275, 1051, 821
6e	White solid	78	113—115	389.0688	3474, 3415, 2926, 1625, 1459, 1268, 1102, 1053, 836
6f	White solid	82	109—110	389.0681	3473, 3416, 1626, 1423, 1122, 1053, 769
6g	Yellow solid	75	115—116	433.0188	3475, 3415, 1626, 1447, 1257, 1121, 1063, 834
6h	Yellow solid	85	155—157	370.1189	3472, 3415, 2926, 1623, 1465, 1278, 1112, 1053, 836
6i	White solid	73	174—175	369.1236	3415, 2920, 1642, 1454, 1269, 1050, 794

Table 1 Appearance, yields, melting points, ESI-TOF-MS and IR data for target compounds 5a—5d, 5f—5i and 6a—6i

Compd.	Appearance	Yield(%)	m.p./℃	ESI-TOF-MS ([M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
5a	White solid	67	76—78	539.1459	3449, 3225, 2961, 1754, 1624, 1586, 1484, 1373, 1227, 1039, 758
5b	White solid	68	178—179	539.1461	3442, 3230, 1751, 1614, 1467, 1401, 1223, 1045, 848
5c	Yellow solid	65	79—80	523.1498	3424, 2958, 1753, 1630, 1549, 1468, 1372, 1226, 1040, 913, 773, 696
5d	White solid	64	84—86	537.1672	3449, 2963, 1751, 1624, 1502, 1435, 1378, 1226, 1041, 824
5f	Yellow solid	63	67—68	557.1107	3446, 2961, 1752, 1635, 1441, 1376, 1226, 1046, 767
5g	Yellow solid	65	153—154	601.0608	3450, 1751, 1635, 1454, 1382, 1226, 1094, 828
5h	Yellow solid	65	122—124	538.1601	3380, 3231, 2959, 1758, 1612, 1471, 1373, 1228, 1040, 838
5i	Yellow solid	67	174—175	537.1641	3448, 2958, 1746, 1637, 1437, 1376, 1241, 1098, 1060, 795
6a	Yellow solid	76	96—97	371.1016	3475, 3417, 1626, 1422, 1129, 773
6b	Yellow solid	74	119—121	371.1017	3416, 2921, 2862, 1620, 1463, 1276, 1172, 1054, 830
6c	Brown solid	82	132—133	355.1075	3471, 3415, 2925, 2861, 1628, 1460, 1273, 1120, 1051, 770, 688
6d	White solid	75	126—127	369.1228	3414, 2920, 1629, 1464, 1275, 1051, 821
6e	White solid	78	113—115	389.0688	3474, 3415, 2926, 1625, 1459, 1268, 1102, 1053, 836
6f	White solid	82	109—110	389.0681	3473, 3416, 1626, 1423, 1122, 1053, 769
6g	Yellow solid	75	115—116	433.0188	3475, 3415, 1626, 1447, 1257, 1121, 1063, 834
6h	Yellow solid	85	155—157	370.1189	3472, 3415, 2926, 1623, 1465, 1278, 1112, 1053, 836
6i	White solid	73	174—175	369.1236	3415, 2920, 1642, 1454, 1269, 1050, 794

Table 2 1H NMR and 13C NMR data for target compounds 5a—5d, 5f—5i and 6a—6i

Compd.	¹H NMR(400 MHz, DMSO-d₆), δ	¹³C NMR(400 MHz, DMSO-d₆), δ
5a	10.55(s, 1H, OH), 7.41(d, 1H, J=7.6 Hz, ArH), 7.36(t, 1H, J=8.0 Hz, ArH), 6.98—6.91(m, 2H, ArH), 5.56(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.41( t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.05(t, 1H, J_H2'-H1'=9.6 Hz, J_H2'-H3'=10.0 Hz, H2'), 4.95(t, 1H, J_H4'-H5_'=J_H4'-H3'=9.6 Hz, H4'), 4.16( dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6''=12.0 Hz, H6'), 4.11(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.06—3.96(m, 1H, H5'), 2.02, 1.99, 1.97, 1.95(4s, 12H, CH₃CO)	170.59, 169.92, 169.56, 169.27, 157.53, 153.74, 133.21, 132.26, 127.03, 119.87, 119.00, 117.97, 85.83, 82.92, 73.26, 69.93, 67.79, 61.55, 20.68, 20.62, 20.53, 20.26
5b	9.93(s, 1H, OH), 7.89(d, 2H, J=8.8 Hz, ArH), 6.88(d, 2H, J=8.4 Hz, ArH), 6.00( s, 2H, NH₂), 5.52( d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.38(t, 1H, J_H3'-H4'=J_H3'-H2'=9.6 Hz, H3'), 5.02(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 4.97(t, 1H, J_H4'-H5'=J_H4'-H3'=9.6 Hz, H4'), 4.12(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=12.0 Hz, H6'), 4.07(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.03—3.99(m, 1H, H5'), 2.08, 1.99, 1.96, 1.89(4s, 12H, CH₃CO)	170.43, 169.96, 169.72, 169.61, 159.44, 154.87, 148.38, 130.00, 117.96, 115.69, 83.13, 75.14, 73.30, 70.38, 68.22, 62.23, 20.88, 20.82, 20.78, 20.73
5c	8.04(dd, 1H, J=1.6, 8.0 Hz, ArH), 7.75—7.73(m, 1H, ArH), 7.53—7.51(m, 3H, ArH), 6.10(s, 2H, NH₂), 5.58(d, 1H, J_H1'-H2'=10.4 Hz, H1'), 5.40(t, 1H, J_H3'-H4'=J_H3'-H2'=9.6 Hz, H3'), 5.04(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 4.95(t, 1H, J_H4'-H5'=J_H4'-H3'=9.6 Hz, H4'), 4.14(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=12.0 Hz, H6'), 4.0(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.04—3.96(m, 1H, H5'), 2.07, 1.99, 1.96, 1.89(4s, 12H, CH₃CO)	174.54, 169.94, 169.66, 169.41, 155.05, 151.00, 128.85, 128.64, 128.55, 128.49, 128.16, 127.31, 85.99, 76.34, 73.26, 69.97, 67.91, 61.75, 20.67, 20.55, 20.51, 20.37
5d	7.87(d, 2H, J=7.6 Hz, ArH), 7.36(d, 1H, J=6.0 Hz, ArH), 7.30(d, 1H, J=4.8 Hz, ArH), 5.36(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.22(t, 1H, J_H3'-H4'=J_H3'-H2'=8.0 Hz, H3'), 4.92(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 4.97( t, 1H, J_H4'-H5'=J_H4'-H3'=9.6 Hz, H4'), 4.14(d, 1H, J=11.6 Hz, H6'), 4.11(d, 1H, J=11.6 Hz, H6″), 4.04—3.99(m, 1H, H5'), 2.37(s, 3H, CH₃), 2.02, 1.99, 1.96, 1.94(4s, 12H, CH₃CO)	170.46, 170.17, 169.87, 169.65, 130.04, 126.45, 89.46, 82.94, 75.19, 73.43, 71.29, 70.49, 69.85, 68.99, 68.42, 66.76, 62.61, 62.24, 21.44, 21.00, 20.93, 20.83, 20.75
5f	7.64(dd, 1H, J=2.8, 5.2 Hz, ArH), 7.60—7.56(m, 1H, ArH), 7.50—7.49(m, 2H, ArH), 5.59(d, 1H, J_H1'-H2'=10.4 Hz, H1'), 5.43(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.06(t, 1H, J_H2'-H1'=J_H2'-H3'=9.6 Hz, H2'), 4.96(t, 1H, J_H4'-H5'= 9.6 Hz, J_H4'-H3'=10 Hz, H4'), 4.15(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=12.0 Hz, H6'), 4.11(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.04—3.96(m, 1H, H5'), 2.10, 2.03, 1.99, 1.98(4s, 12H, CH₃CO)	170.41, 169.95, 169.72, 169.58, 149.21, 133.66, 132.82, 132.45, 130.26, 127.72, 126.45, 83.07, 75.24, 73.32, 70.49, 68.22, 62.17, 20.90, 20.86, 20.79, 20.71
5g	8.03(d, 2H, J=8.8 Hz, ArH), 7.76(d, 2H, J=8.4 Hz, ArH)6.10(s, 2H, NH₂), 5.57(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.39(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.05(t, 1H, J_H2'-H1'=9.6 Hz, J_H2'-H3'=10.0 Hz, H2'), 4.98(t, 1H, J_H4'-H5'=9.2 Hz, J_H4'-H3'=9.6 Hz, H4'), 4.13(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=11.6 Hz, H6'), 4.08(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.03—4.00(m, 1H, H5'), 2.06, 1.99, 1.96, 1.90(4s, 12H, CH₃CO)	170.41, 169.96, 169.72, 169.62, 153.92, 149.62, 132.04, 130.23, 126.45, 123.99, 82.93, 75.19, 73.31, 70.37, 68.19, 62.19, 20.88, 20.82, 20.81, 20.74
5h	7.39(d, 2H, J=8.8 Hz, ArH), 6.61(d, 2H, J=8.4 Hz, ArH), 5.63(s, 2H, NH₂), 5.44(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.39(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.01(t, 1H, J_H2'-H1'=J_H2'-H3'=9.6 Hz, H2'), 4.93(t, 1H, J_H4'-H5'=8.8 Hz, J_H4'-H3'=9.6 Hz, H4'), 4.15(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=11.6 Hz, H6'), 4.11(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 3.97—3.94(m, 1H, H5'), 2.03, 1.99, 1.96, 1.94(4s, 12H, CH₃CO)	170.37, 169.94, 169.72, 169.52, 151.49, 150.78, 129.46, 128.45, 114.15, 113.70, 83.58, 75.14, 73.33, 70.65, 68.18, 62.14, 20.88, 20.79, 20.71, 20.39
5i	7.86(s, 1H, ArH), 7.84(d, 1H, J=7.6 Hz, ArH), 7.42(t, 1H, J=7.6 Hz, ArH), 7.34(d, 1H, J=7.6 Hz, ArH), 6.07(s, 2H, NH₂), 5.57(d, 1H, J_H1'-H2'=10.4 Hz, H1'), 5.40(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.04(t, 1H, J_H2'-H1'=9.6 Hz, J_H2'-H3'=10.0 Hz, H2'), 4.98(t, 1H, J_H4'-H5'=9.6 Hz, J_H4'-H3'=10 Hz, H4'), 4.07—4.15(m, 2H, H6', H6″), 4.02(d, 1H, J_H5'-H6'=10.4 Hz, H5'), 2.39(s, 3H, CH₃), 2.07, 1.99, 1.96, 1.90(4s, 12H, CH₃CO)	170.43, 169.98, 169.73, 169.63, 149.16, 138.16, 130.95, 128.84, 128.83, 127.16, 125.57, 82.99, 75.19, 73.33, 70.39, 68.22, 62.21, 21.46, 20.86, 20.80, 20.76, 20.71
6a	7.44—7.36(m, 1H, ArH), 7.03—6.95(m, 2H, ArH), 6.60(d, 1H, J=6.4 Hz, ArH), 6.22(s, 2H, NH₂), 5.64—5.57(m, 1H, H1'), 5.22—5.18(m, 1H, H3'), 4.91—4.86(m, 2H, H2', H4'), 4.52—4.47(m, 1H, H6'), 4.37—4.25(m, 1H, H6″), 3.68—3.58(m, 1H, H5'), 3.17—3.04(m, 4H, OH)	156.62, 154.01, 150.15, 132.03, 129.59, 119.46, 117.06, 113.11, 86.89, 81.66, 78.34, 73.37, 70.02, 61.25
6b	9.93(s, 1H, OH), 7.89(d, 2H, J=8.8 Hz, ArH), 6.88(d, 2H, J=8.8 Hz, ArH), 6.04(s, 2H, NH₂), 5.55(d, 1H, J=6.4 Hz, H1'), 5.18(d, 1H, J=12.0 Hz, H3'), 5.04(d, 1H, J=4.8 Hz, H2'), 4.75(d, 1H, J=10.0 Hz, H4'), 4.63(t, 1H, J=5.2, 10.4 Hz, H6'), 3.88—3.58(m, 2H, H5', H6″), 3.20—3.07(m, 4H, OH)	159.30, 154.73, 149.11, 130.06, 118.34, 115.63, 87.68, 81.52, 78.24, 73.37, 70.12, 61.39
6c	8.05(t, 2H, J=3.2, 7.6 Hz, ArH), 7.53(dd, 3H, J=2.8, 7.6 Hz, ArH), 6.12(s, 2H, NH₂), 5.58(d, 1H, J=6.4 Hz, H1'), 5.21(d, 1H, J=4.8 Hz, H3'), 5.06(t, 1H, J=8.4, 3.6 Hz, H2'), 4.81(d, 1H, J=9.6 Hz, H4'), 4.64(t, 1H, J=5.2, 10.8 Hz, H6'), 3.68—3.61(m, 2H, H5', H6″), 3.21—3.16(m, 4H, OH)	154.63, 150.03, 130.20, 129.39, 128.86, 128.48, 87.56, 81.57, 78.25, 73.41, 70.12, 61.37
6d	7.95(d, 2H, J=8.0 Hz, ArH), 7.34(d, 2H, J=8.0 Hz, ArH), 6.10(s, 2H, NH₂), 5.60(d, 1H, J=6.0 Hz, H1'), 5.23(d, 1H, J=4.8 Hz, H3'), 5.07(d, 1H, J=5.6 Hz, H2'), 4.80(d, 1H, J=9.6 Hz, H4), 4.66(t, 1H, J=5.6, 10.8 Hz, H6'), 3.44—3.39(m, 2H, H5', H6'), 3.19—3.09(m, 4H, OH), 2.37(s, 3H, CH₃)	154.65, 149.76, 139.91, 129.42, 128.38, 124.73, 87.60, 81.54, 78.25, 73.38, 70.12, 61.39, 21.45
6e	8.10(d, 1H, J=8.8 Hz, ArH), 7.75(d, 1H, J=8.4 Hz, ArH), 7.62(t, 2H, J=8.4, 8.4 Hz, ArH), 6.14(s, 2H, NH₂), 5.58(d, 1H, J=6.0 Hz, H1'), 5.20(d, 1H, J=5.2 Hz, H3'), 5.05(d, 1H, J=5.6 Hz, H2'), 4.95(d, 1H, J=10.8 Hz, H4'), 4.80(d, 1H, J=9.6 Hz, H6'), 3.68—3.61(m, 2H, H5', H6'), 3.22—3.12(m, 4H, OH)	153.68, 150.32, 129.65, 129.34, 129.04, 87.59, 81.55, 78.34, 73.38, 70.12, 61.39
6f	7.63(d, 1H, J=8.0 Hz, ArH), 7.59—7.55(m, 1H, ArH), 7.49(d, 2H, J=4.0 Hz, ArH), 5.54(d, 1H, J=6.0 Hz, H1'), 5.24(d, 1H, J=4.8 Hz, H3'), 5.05(t, 2H, J=4.0, 5.2 Hz, H2', H4'), 4.46(t, 1H, J=5.6, 11.2 Hz, H6'), 3.64—3.60(m, 1H, H6″), 3.45—3.41(m, 1H, H5'), 3.22—3.16(m, 4H, OH)	149.45, 144.97, 133.44, 132.66, 132.61, 130.41, 127.90, 126.31, 86.94, 81.78, 78.43, 73.30, 69.92, 61.23
6g	8.03(d, 1H, J=8.4 Hz, ArH), 7.75(t, 2H, J=8.4, 8.4 Hz, ArH), 7.69(d, 1H, J=8.4 Hz, ArH), 6.15(s, 2H, NH₂), 5.60(d, 1H, J=5.6 Hz, H1'), 5.22(d, 1H, J=4.8 Hz, H3'), 5.07(d, 1H, J=5.2 Hz, H2'), 4.96(d, 1H, J=10.0 Hz, H4'), 4.81(d, 1H, J=9.6 Hz, H6'), 4.65(t, 1H, J=5.2, 10.8 Hz, H6″), 3.43—3.40(m, 1H, H5'), 3.22—3.13(m, 4H, OH)	153.74, 150.38, 132.57, 131.97, 130.33, 129.51, 87.58, 81.56, 78.34, 73.39, 70.12, 61.39
6h	7.75(d, 2H, J=8.4 Hz, ArH), 6.62(d, 2H, J=8.4 Hz, ArH), 5.99(s, 2H, NH₂), 5.55(s, 1H, H1'), 5.19(d, 1H, J=4.4 Hz, H3'), 5.04(d, 1H, J=5.2 Hz, H2'), 4.72(d, 1H, J=9.6 Hz, H4'), 4.64(t, 1H, J=5.2, 10.8 Hz, H6'), 4.13(d, 1H, J=5.2 Hz, H6″), 3.65—3.61(m, 1H, H5'), 3.17—3.16(m, 4H, OH)	155.13, 150.70, 148.47, 129.49, 114.56, 113.52, 87.76, 81.52, 78.25, 73.37, 70.13, 61.39
6i	7.84(t, 1H, J=9.2 Hz, ArH), 7.55—7.49(m, 1H, ArH), 7.44—7.31(m, 2H, ArH), 6.10(s, 2H, NH₂), 5.57(d, 1H, J=6.4 Hz, H1'), 5.19(t, 1H, J=5.2, 10.0 Hz, H3'), 5.07—5.03(m, 1H, H2'), 4.98—4.88(m, 1H, H4'), 4.85—4.78(m, 1H, H6'), 4.65—3.51(m, 1H, H6″), 3.66—3.62(m, 1H, H5'), 3.26—3.17(m, 4H, OH), 2.38(s, 3H, CH₃)	154.72, 150.00, 138.07, 131.57, 130.83, 128.95, 128.77, 125.67, 87.51, 81.55, 78.24, 73.34, 70.09, 61.35, 21.52

Table 2 1H NMR and 13C NMR data for target compounds 5a—5d, 5f—5i and 6a—6i

Compd.	¹H NMR(400 MHz, DMSO-d₆), δ	¹³C NMR(400 MHz, DMSO-d₆), δ
5a	10.55(s, 1H, OH), 7.41(d, 1H, J=7.6 Hz, ArH), 7.36(t, 1H, J=8.0 Hz, ArH), 6.98—6.91(m, 2H, ArH), 5.56(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.41( t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.05(t, 1H, J_H2'-H1'=9.6 Hz, J_H2'-H3'=10.0 Hz, H2'), 4.95(t, 1H, J_H4'-H5_'=J_H4'-H3'=9.6 Hz, H4'), 4.16( dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6''=12.0 Hz, H6'), 4.11(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.06—3.96(m, 1H, H5'), 2.02, 1.99, 1.97, 1.95(4s, 12H, CH₃CO)	170.59, 169.92, 169.56, 169.27, 157.53, 153.74, 133.21, 132.26, 127.03, 119.87, 119.00, 117.97, 85.83, 82.92, 73.26, 69.93, 67.79, 61.55, 20.68, 20.62, 20.53, 20.26
5b	9.93(s, 1H, OH), 7.89(d, 2H, J=8.8 Hz, ArH), 6.88(d, 2H, J=8.4 Hz, ArH), 6.00( s, 2H, NH₂), 5.52( d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.38(t, 1H, J_H3'-H4'=J_H3'-H2'=9.6 Hz, H3'), 5.02(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 4.97(t, 1H, J_H4'-H5'=J_H4'-H3'=9.6 Hz, H4'), 4.12(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=12.0 Hz, H6'), 4.07(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.03—3.99(m, 1H, H5'), 2.08, 1.99, 1.96, 1.89(4s, 12H, CH₃CO)	170.43, 169.96, 169.72, 169.61, 159.44, 154.87, 148.38, 130.00, 117.96, 115.69, 83.13, 75.14, 73.30, 70.38, 68.22, 62.23, 20.88, 20.82, 20.78, 20.73
5c	8.04(dd, 1H, J=1.6, 8.0 Hz, ArH), 7.75—7.73(m, 1H, ArH), 7.53—7.51(m, 3H, ArH), 6.10(s, 2H, NH₂), 5.58(d, 1H, J_H1'-H2'=10.4 Hz, H1'), 5.40(t, 1H, J_H3'-H4'=J_H3'-H2'=9.6 Hz, H3'), 5.04(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 4.95(t, 1H, J_H4'-H5'=J_H4'-H3'=9.6 Hz, H4'), 4.14(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=12.0 Hz, H6'), 4.0(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.04—3.96(m, 1H, H5'), 2.07, 1.99, 1.96, 1.89(4s, 12H, CH₃CO)	174.54, 169.94, 169.66, 169.41, 155.05, 151.00, 128.85, 128.64, 128.55, 128.49, 128.16, 127.31, 85.99, 76.34, 73.26, 69.97, 67.91, 61.75, 20.67, 20.55, 20.51, 20.37
5d	7.87(d, 2H, J=7.6 Hz, ArH), 7.36(d, 1H, J=6.0 Hz, ArH), 7.30(d, 1H, J=4.8 Hz, ArH), 5.36(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.22(t, 1H, J_H3'-H4'=J_H3'-H2'=8.0 Hz, H3'), 4.92(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 4.97( t, 1H, J_H4'-H5'=J_H4'-H3'=9.6 Hz, H4'), 4.14(d, 1H, J=11.6 Hz, H6'), 4.11(d, 1H, J=11.6 Hz, H6″), 4.04—3.99(m, 1H, H5'), 2.37(s, 3H, CH₃), 2.02, 1.99, 1.96, 1.94(4s, 12H, CH₃CO)	170.46, 170.17, 169.87, 169.65, 130.04, 126.45, 89.46, 82.94, 75.19, 73.43, 71.29, 70.49, 69.85, 68.99, 68.42, 66.76, 62.61, 62.24, 21.44, 21.00, 20.93, 20.83, 20.75
5f	7.64(dd, 1H, J=2.8, 5.2 Hz, ArH), 7.60—7.56(m, 1H, ArH), 7.50—7.49(m, 2H, ArH), 5.59(d, 1H, J_H1'-H2'=10.4 Hz, H1'), 5.43(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.06(t, 1H, J_H2'-H1'=J_H2'-H3'=9.6 Hz, H2'), 4.96(t, 1H, J_H4'-H5'= 9.6 Hz, J_H4'-H3'=10 Hz, H4'), 4.15(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=12.0 Hz, H6'), 4.11(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.04—3.96(m, 1H, H5'), 2.10, 2.03, 1.99, 1.98(4s, 12H, CH₃CO)	170.41, 169.95, 169.72, 169.58, 149.21, 133.66, 132.82, 132.45, 130.26, 127.72, 126.45, 83.07, 75.24, 73.32, 70.49, 68.22, 62.17, 20.90, 20.86, 20.79, 20.71
5g	8.03(d, 2H, J=8.8 Hz, ArH), 7.76(d, 2H, J=8.4 Hz, ArH)6.10(s, 2H, NH₂), 5.57(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.39(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.05(t, 1H, J_H2'-H1'=9.6 Hz, J_H2'-H3'=10.0 Hz, H2'), 4.98(t, 1H, J_H4'-H5'=9.2 Hz, J_H4'-H3'=9.6 Hz, H4'), 4.13(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=11.6 Hz, H6'), 4.08(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 4.03—4.00(m, 1H, H5'), 2.06, 1.99, 1.96, 1.90(4s, 12H, CH₃CO)	170.41, 169.96, 169.72, 169.62, 153.92, 149.62, 132.04, 130.23, 126.45, 123.99, 82.93, 75.19, 73.31, 70.37, 68.19, 62.19, 20.88, 20.82, 20.81, 20.74
5h	7.39(d, 2H, J=8.8 Hz, ArH), 6.61(d, 2H, J=8.4 Hz, ArH), 5.63(s, 2H, NH₂), 5.44(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.39(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.01(t, 1H, J_H2'-H1'=J_H2'-H3'=9.6 Hz, H2'), 4.93(t, 1H, J_H4'-H5'=8.8 Hz, J_H4'-H3'=9.6 Hz, H4'), 4.15(dd, 1H, J_H6'-H5'=5.2 Hz, J_H6'-H6″=11.6 Hz, H6'), 4.11(dd, 1H, J_H6″-H5'=5.2 Hz, J_H6″-H6'=12.0 Hz, H6″), 3.97—3.94(m, 1H, H5'), 2.03, 1.99, 1.96, 1.94(4s, 12H, CH₃CO)	170.37, 169.94, 169.72, 169.52, 151.49, 150.78, 129.46, 128.45, 114.15, 113.70, 83.58, 75.14, 73.33, 70.65, 68.18, 62.14, 20.88, 20.79, 20.71, 20.39
5i	7.86(s, 1H, ArH), 7.84(d, 1H, J=7.6 Hz, ArH), 7.42(t, 1H, J=7.6 Hz, ArH), 7.34(d, 1H, J=7.6 Hz, ArH), 6.07(s, 2H, NH₂), 5.57(d, 1H, J_H1'-H2'=10.4 Hz, H1'), 5.40(t, 1H, J_H3'-H4'=9.6 Hz, J_H3'-H2'=9.2 Hz, H3'), 5.04(t, 1H, J_H2'-H1'=9.6 Hz, J_H2'-H3'=10.0 Hz, H2'), 4.98(t, 1H, J_H4'-H5'=9.6 Hz, J_H4'-H3'=10 Hz, H4'), 4.07—4.15(m, 2H, H6', H6″), 4.02(d, 1H, J_H5'-H6'=10.4 Hz, H5'), 2.39(s, 3H, CH₃), 2.07, 1.99, 1.96, 1.90(4s, 12H, CH₃CO)	170.43, 169.98, 169.73, 169.63, 149.16, 138.16, 130.95, 128.84, 128.83, 127.16, 125.57, 82.99, 75.19, 73.33, 70.39, 68.22, 62.21, 21.46, 20.86, 20.80, 20.76, 20.71
6a	7.44—7.36(m, 1H, ArH), 7.03—6.95(m, 2H, ArH), 6.60(d, 1H, J=6.4 Hz, ArH), 6.22(s, 2H, NH₂), 5.64—5.57(m, 1H, H1'), 5.22—5.18(m, 1H, H3'), 4.91—4.86(m, 2H, H2', H4'), 4.52—4.47(m, 1H, H6'), 4.37—4.25(m, 1H, H6″), 3.68—3.58(m, 1H, H5'), 3.17—3.04(m, 4H, OH)	156.62, 154.01, 150.15, 132.03, 129.59, 119.46, 117.06, 113.11, 86.89, 81.66, 78.34, 73.37, 70.02, 61.25
6b	9.93(s, 1H, OH), 7.89(d, 2H, J=8.8 Hz, ArH), 6.88(d, 2H, J=8.8 Hz, ArH), 6.04(s, 2H, NH₂), 5.55(d, 1H, J=6.4 Hz, H1'), 5.18(d, 1H, J=12.0 Hz, H3'), 5.04(d, 1H, J=4.8 Hz, H2'), 4.75(d, 1H, J=10.0 Hz, H4'), 4.63(t, 1H, J=5.2, 10.4 Hz, H6'), 3.88—3.58(m, 2H, H5', H6″), 3.20—3.07(m, 4H, OH)	159.30, 154.73, 149.11, 130.06, 118.34, 115.63, 87.68, 81.52, 78.24, 73.37, 70.12, 61.39
6c	8.05(t, 2H, J=3.2, 7.6 Hz, ArH), 7.53(dd, 3H, J=2.8, 7.6 Hz, ArH), 6.12(s, 2H, NH₂), 5.58(d, 1H, J=6.4 Hz, H1'), 5.21(d, 1H, J=4.8 Hz, H3'), 5.06(t, 1H, J=8.4, 3.6 Hz, H2'), 4.81(d, 1H, J=9.6 Hz, H4'), 4.64(t, 1H, J=5.2, 10.8 Hz, H6'), 3.68—3.61(m, 2H, H5', H6″), 3.21—3.16(m, 4H, OH)	154.63, 150.03, 130.20, 129.39, 128.86, 128.48, 87.56, 81.57, 78.25, 73.41, 70.12, 61.37
6d	7.95(d, 2H, J=8.0 Hz, ArH), 7.34(d, 2H, J=8.0 Hz, ArH), 6.10(s, 2H, NH₂), 5.60(d, 1H, J=6.0 Hz, H1'), 5.23(d, 1H, J=4.8 Hz, H3'), 5.07(d, 1H, J=5.6 Hz, H2'), 4.80(d, 1H, J=9.6 Hz, H4), 4.66(t, 1H, J=5.6, 10.8 Hz, H6'), 3.44—3.39(m, 2H, H5', H6'), 3.19—3.09(m, 4H, OH), 2.37(s, 3H, CH₃)	154.65, 149.76, 139.91, 129.42, 128.38, 124.73, 87.60, 81.54, 78.25, 73.38, 70.12, 61.39, 21.45
6e	8.10(d, 1H, J=8.8 Hz, ArH), 7.75(d, 1H, J=8.4 Hz, ArH), 7.62(t, 2H, J=8.4, 8.4 Hz, ArH), 6.14(s, 2H, NH₂), 5.58(d, 1H, J=6.0 Hz, H1'), 5.20(d, 1H, J=5.2 Hz, H3'), 5.05(d, 1H, J=5.6 Hz, H2'), 4.95(d, 1H, J=10.8 Hz, H4'), 4.80(d, 1H, J=9.6 Hz, H6'), 3.68—3.61(m, 2H, H5', H6'), 3.22—3.12(m, 4H, OH)	153.68, 150.32, 129.65, 129.34, 129.04, 87.59, 81.55, 78.34, 73.38, 70.12, 61.39
6f	7.63(d, 1H, J=8.0 Hz, ArH), 7.59—7.55(m, 1H, ArH), 7.49(d, 2H, J=4.0 Hz, ArH), 5.54(d, 1H, J=6.0 Hz, H1'), 5.24(d, 1H, J=4.8 Hz, H3'), 5.05(t, 2H, J=4.0, 5.2 Hz, H2', H4'), 4.46(t, 1H, J=5.6, 11.2 Hz, H6'), 3.64—3.60(m, 1H, H6″), 3.45—3.41(m, 1H, H5'), 3.22—3.16(m, 4H, OH)	149.45, 144.97, 133.44, 132.66, 132.61, 130.41, 127.90, 126.31, 86.94, 81.78, 78.43, 73.30, 69.92, 61.23
6g	8.03(d, 1H, J=8.4 Hz, ArH), 7.75(t, 2H, J=8.4, 8.4 Hz, ArH), 7.69(d, 1H, J=8.4 Hz, ArH), 6.15(s, 2H, NH₂), 5.60(d, 1H, J=5.6 Hz, H1'), 5.22(d, 1H, J=4.8 Hz, H3'), 5.07(d, 1H, J=5.2 Hz, H2'), 4.96(d, 1H, J=10.0 Hz, H4'), 4.81(d, 1H, J=9.6 Hz, H6'), 4.65(t, 1H, J=5.2, 10.8 Hz, H6″), 3.43—3.40(m, 1H, H5'), 3.22—3.13(m, 4H, OH)	153.74, 150.38, 132.57, 131.97, 130.33, 129.51, 87.58, 81.56, 78.34, 73.39, 70.12, 61.39
6h	7.75(d, 2H, J=8.4 Hz, ArH), 6.62(d, 2H, J=8.4 Hz, ArH), 5.99(s, 2H, NH₂), 5.55(s, 1H, H1'), 5.19(d, 1H, J=4.4 Hz, H3'), 5.04(d, 1H, J=5.2 Hz, H2'), 4.72(d, 1H, J=9.6 Hz, H4'), 4.64(t, 1H, J=5.2, 10.8 Hz, H6'), 4.13(d, 1H, J=5.2 Hz, H6″), 3.65—3.61(m, 1H, H5'), 3.17—3.16(m, 4H, OH)	155.13, 150.70, 148.47, 129.49, 114.56, 113.52, 87.76, 81.52, 78.25, 73.37, 70.13, 61.39
6i	7.84(t, 1H, J=9.2 Hz, ArH), 7.55—7.49(m, 1H, ArH), 7.44—7.31(m, 2H, ArH), 6.10(s, 2H, NH₂), 5.57(d, 1H, J=6.4 Hz, H1'), 5.19(t, 1H, J=5.2, 10.0 Hz, H3'), 5.07—5.03(m, 1H, H2'), 4.98—4.88(m, 1H, H4'), 4.85—4.78(m, 1H, H6'), 4.65—3.51(m, 1H, H6″), 3.66—3.62(m, 1H, H5'), 3.26—3.17(m, 4H, OH), 2.38(s, 3H, CH₃)	154.72, 150.00, 138.07, 131.57, 130.83, 128.95, 128.77, 125.67, 87.51, 81.55, 78.24, 73.34, 70.09, 61.35, 21.52

Table 3 In vitro antimicrobial activities for target compounds expressed as MIC

Compd.	MIC/(μg·mL^-1)				Compd.	MIC/(μg·mL^-1)
Compd.	B.s.		S.a.	E.c.	M.a.	B.s.	S.a.	E.c.	M.a.
5a	128	64	128	8	6a	64	4	8	8
5b	128	64	64	2	6b	64	16	16	16
5c	64	64	128	16	6c	64	32	8	16
5d	128	64	128	2	6d	32	32	16	16
5e	128	32	64	32	6e	32	8	8	16
5f	128	64	256	2	6f	64	16	16	8
5g	64	16	8	2	6g	32	8	2	8
5h	128	64	128	32	6h	32	32	4	16
5i	128	64	128	2	6i	64	16	8	32
Triclosan	4	4	2	2	Fluconazole	128	16	128	32

Table 4 Binding free energy of the target compounds with FabⅠ

Compd.	Binding free energy/ (kJ·mol^-1)	Compd.	Binding free energy/ (kJ·mol^-1)
5a	-31.05	6a	-33.97
5b	-32.68	6b	-33.47
5c	-29.92	6c	-31.63
5d	-30.67	6d	-32.17
5e	-28.83	6e	-30.75
5f	-24.14	6f	-31.09
5g	-31.84	6g	-33.64
5h	-27.20	6h	-30.00
5i	-28.37	6i	-25.94
TCL	-35.27

Fig.1 Combining three-dimensional space binding modes of docking pose of compounds 5f(A) and 6f(B) with FabⅠ

Fig.2 Binding modes of docking pose of compounds 5f(A) and 6f(B) with FabⅠ

Fig.3 Combining three-dimensional space binding modes of docking pose of compounds 5g(A) and 6g(B) with FabⅠ

Fig.4 Binding modes of docking pose of compounds 5g(A) and 6g(B) with FabⅠ

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