新型1,2,4-三唑并[3,4-b]-1,3,4-噻二唑类化合物的合成、 抗菌活性及与FabⅠ作用的分子模拟

doi:10.7503/cjcu20140907

摘要/Abstract

摘要：

以3-芳基/烷基-4-氨基-5-巯基-1,2,4-三唑为原料, 经过环化和糖化反应, 设计合成了10个未见报道的化合物3-芳基/烷基-6-S-2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑(3a~3j), 其结构经核磁共振波谱、高分辨质谱和红外光谱确认. 生物活性测试表明, 所有化合物均对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念株菌表现出一定的抗菌活性, 其中化合物3c对4种测试菌株的最小抑菌浓度(MIC)最低, 且接近于氟康唑的参照数据, 具有较强的抗菌活性. 利用AutoDock 4.0程序研究了目标化合物3a~3j与大肠杆菌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: 糖苷, 1,2,4-三唑并[3,4-b]-1,3,4-噻二唑, 抗菌活性, FabⅠ受体蛋白

Abstract:

Ten novel compounds of 3-alkyl/aryl-6-S-(2',3',4',6'-tetra-O-acetyl-β-D-glcopyranosyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were designed and synthesized from 3-alkyl/aryl-4-amino-5-mercapto-1,2,4-triazoles. The structures of all the compounds were confirmed by means of ¹H NMR, ¹³C NMR, HRMS and IR. The preliminary bioassay showed that all target compounds possessed efficient antibacterial activities on Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Monilia albican. Especially, the compound 3c had strong antibacterial by the lowest minimal inhibitory concentration(MIC) values on the four tested strains which were close to those of the controlled drug fluconazole. The interaction and binding free energy of the target compounds(3a—3j) with FabⅠ were studied by AutoDock 4.0.

Key words: Glucoside, 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazole, Antibacterial, FabⅠ

中图分类号:

O626.26

TrendMD:

王美君, 卢俊瑞, 辛春伟, 刘金彪, 穆江蓓, 张贺, 张瑞波, 杨旭云, 王宏韫. 新型1,2,4-三唑并[3,4-b]-1,3,4-噻二唑类化合物的合成、抗菌活性及与FabⅠ作用的分子模拟. 高等学校化学学报, 2015, 36(3): 469.

WANG Meijun, LU Junrui, XIN Chunwei, LIU Jinbiao, MU Jiangbei, ZHANG He, ZHANG Ruibo, YANG Xuyun, WANG Hongyun. Synthesis, Antibacterial Activity and Molecular Simulation with FabⅠ of a Series of Novel 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazoles^†. Chem. J. Chinese Universities, 2015, 36(3): 469.

图/表 8

Scheme 1 Syntheses of the target compounds 3a—3j a. R=C6H5; b. R=2-OHC6H5; c. R=4-OHC6H5; d. R=4-CH3C6H5; e. R=4-ClC6H5;f. R=2-ClC6H5; g. R=CH3; h. R=C2H5; i. R=C3H7; j. R=C7H15

Table 1 Physiochemical data of the intermediates*

Compd.	m.p./℃	m.p.(ref.)/℃	Compd.	m.p./℃	m.p.(ref.)/℃
A	87.3—88.6	88.5^[23]	1i	107.9—109.3	108—109^[24]
1a	195.9—198.1	204—205^[23]	2a	211.7—213.3	212—213^[25]
1b	175.6—177.3	177.1^[23]	2c	167.3—169.1	257^[26]
1c	267.2—269.6	>250^[23]	2d	210.3—212.5	208^[25]
1d	214.3—215.2	213^[23]	2e	191.4—193.7	134—135^[25]
1e	205.7—208.2	211—213^[23]	2f	179.3—181.7	171—172^[25]
1f	147.4—148.6	152^[23]	2g	240.7—242.8	235^[27]
1g	197.3—199.1	208—210^[24]	2h	225.3—227.9	222^[27]
1h	150.6—154.6	144^[24]

Table 2 Physiochemical data, IR and MS data of intermediate 2b and target compounds 3a—3j

Compd.	Appearance	Yield(%)	m.p./℃	IR(KBr), $ν ˙$ /cm^-1	ESI-TOF-MS ([M+H]⁺), m/z
2b	Pale yellow solid	81.4	150.3—152.5	3121, 2134, 1645, 1575, 1476, 1238, 765	251.0060
3a	White solid	50.3	94.4—96.9	3131, 2356, 1747, 1635, 1575, 1375, 917, 889, 773, 618	565.1069
3b	White solid	57.7	96.9—98.4	3421, 3163, 2360, 1752, 1639, 1582, 1374, 918, 893, 773, 620	581.1009
3c	White solid	68.2	139.8—142.3	3441, 3113, 2361, 1752, 1614, 1548, 1380, 917, 893, 776, 619	581.1008
3d	White solid	68.9	92.7—94.8	3135, 2361, 1746, 1643, 1554, 1387, 1046, 919, 898, 775, 645, 630	570.1223
3e	White solid	63.4	186.8—189.2	3180, 2364, 1745, 1655, 1551, 1385, 921, 896, 774, 617	599.0670
3f	Pale yellow solid	59.4	53.4—55.7	3164, 2362, 1745, 1636, 1582, 1376, 919, 891, 779, 619	599.0668
3g	White solid	54.9	155.5—157.2	1751, 1655, 1602, 1385, 920, 898, 778, 618	503.0900
3h	White solid	52.67	146.1—148.7	1743, 1635, 1378, 923, 897, 778, 619	517.1068
3i	White solid	54.8	109.2—111.7	1743, 1636, 1378, 919, 892, 778, 617	531.1215
3j	Pale yellow solid	51.7	76.3—77.7	1747, 1636, 1378, 920, 897, 779, 616	587.1849

Table 2 Physiochemical data, IR and MS data of intermediate 2b and target compounds 3a—3j

Compd.	Appearance	Yield(%)	m.p./℃	IR(KBr), $ν ˙$ /cm^-1	ESI-TOF-MS ([M+H]⁺), m/z
2b	Pale yellow solid	81.4	150.3—152.5	3121, 2134, 1645, 1575, 1476, 1238, 765	251.0060
3a	White solid	50.3	94.4—96.9	3131, 2356, 1747, 1635, 1575, 1375, 917, 889, 773, 618	565.1069
3b	White solid	57.7	96.9—98.4	3421, 3163, 2360, 1752, 1639, 1582, 1374, 918, 893, 773, 620	581.1009
3c	White solid	68.2	139.8—142.3	3441, 3113, 2361, 1752, 1614, 1548, 1380, 917, 893, 776, 619	581.1008
3d	White solid	68.9	92.7—94.8	3135, 2361, 1746, 1643, 1554, 1387, 1046, 919, 898, 775, 645, 630	570.1223
3e	White solid	63.4	186.8—189.2	3180, 2364, 1745, 1655, 1551, 1385, 921, 896, 774, 617	599.0670
3f	Pale yellow solid	59.4	53.4—55.7	3164, 2362, 1745, 1636, 1582, 1376, 919, 891, 779, 619	599.0668
3g	White solid	54.9	155.5—157.2	1751, 1655, 1602, 1385, 920, 898, 778, 618	503.0900
3h	White solid	52.67	146.1—148.7	1743, 1635, 1378, 923, 897, 778, 619	517.1068
3i	White solid	54.8	109.2—111.7	1743, 1636, 1378, 919, 892, 778, 617	531.1215
3j	Pale yellow solid	51.7	76.3—77.7	1747, 1636, 1378, 920, 897, 779, 616	587.1849

Table 3 1H NMR and 13C NMR data of intermediate 2b and target compounds 3a—3j

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(400 MHz, CDCl₃), δ
2b	13.8(s, 1H, SH), 11.06(s, 1H, OH), 8.41(d, 1H, J=6.7 Hz, ArH), 7.49(t, 1H, J=6.3 Hz, ArH), 7.12(t, 2H, J=6.3 Hz, ArH)	157.02, 155.98, 155.32, 134.09, 132.41, 129.14, 128.68, 119.89, 116.93
3a	8.32(d, 2H, J=7.12 Hz, ArH), 7.55(m, 3H, ArH) 5.36(m, 1H, H1'), 5.24(m, 2H, H2, H3'), 5.18(t, 1H, $J H 4' - H 5'$ =9.8 Hz, J_H4'-H3'=9.6 Hz, H4'), 4.31(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=5.1 Hz, H6″), 4.23(dd, 1H, J_H6'-H6″=12.4 Hz, J_H6'-H5'=2.1 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.4 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 2.13, 2.08, 2.05, 2.04(4s, 12H, 4CH₃CO)	170.48, 170.16, 169.96, 169.27, 161.47, 154.76, 146.32, 130.62, 128.99, 128.65, 126.44, 125.70, 125.58, 83.73, 73.23, 69.70, 69.51, 67.68, 61.67, 20.68, 20.63, 20.55, 20.51
3b	10.97(s, 1H, OH), 7.94(d, 1H, J=7.7 Hz, ArH), 7.36(t, 1H, J=7.6 Hz, ArH), 7.02(d, 1H, J=8.2 Hz, ArH), 6.97(t, 1H, J=7.6 Hz, ArH), 5.65(d, 1H, J_H1'-H2'=10.2 Hz, H1'), 5.46(t, 1H, $J H 2' - H 1'$ =J_H2'-H3'=9.4 Hz, H2'), 5.08(t, 1H, J_H3'-H4'=J_H3'-H2'=9.7 Hz, H3'), 4.96(t, 1H, J_H4'-H5'=J_H4'-H3'=9.5 Hz, H4'), 4.23(m, 2H, H6″, H6'), 3.99(ddd, 1H, J_H5'-H4'=10.7 Hz, $J H 5' - H 6 ″$ =4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 2.00, 1.99, 1.95, 1.93(4s, 12H, 4CH₃CO)	170.41, 169.94, 169.73, 169.57, 156.28, 155.14, 153.55, 132.35, 127.93, 120.08, 119.92, 117.22, 112.48, 82.63, 75.26, 73.42, 70.34, 68.43, 62.20, 21.49, 20.91, 20.80, 20.72
3c	10.13(s, 1H, OH), 8.04(d, 2H, J=8.7 Hz, ArH), 6.97(d, 2H, J=8.7 Hz, ArH), 5.76(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.48(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 5.14(t, 1H, J_H3'-H4'=J_H3'-H2'=9.7 Hz, H3'), 5.07(t, 1H, J_H4'-H5'=J_H4'-H3'=9.7 Hz, H4'), 4.21(m, 3H, H6″, H6', H5'), 2.09, 2.07, 2.02, 1.96(4s, 12H, 4CH₃CO)	170.38, 169.95, 169.75, 169.71, 159.98, 154.62, 145.81, 132.50, 128.17, 124.43, 120.09, 116.49, 116.43, 82.52, 75.65, 72.94, 69.74, 68.17, 62.17, 20.90, 20.83, 20.79, 20.71
3d	8.19(d, 2H, J=8.0 Hz, ArH), 7.36(d, 2H, J=8.0 Hz, ArH), 5.36(d, 1H, J_H1'-H2'=8.6 Hz, H1'), 5.24(m, 2H, H2', H3'), 5.18(t, 1H, J_H4'-H5'=J_H4'-H3'=9.7 Hz, H4'), 4.32(dd, 1H, J_H6″-H6'=12.5 Hz, J_H6″-H5'=5.1 Hz, H6″), 4.22(dd, 1H, J_H6'-H6″=11.9 Hz, J_H6'-H5'=2.0 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=5.1 Hz, J_H5'-H6'=2.0 Hz, H5'), 2.45(s, 3H, CH₃), 2.13, 2.08, 2.05, 2.04(4s, 12H, 4CH₃CO)	170.46, 169.94, 169.38, 169.24, 161.06, 154.42, 146.48, 140.91, 129.65, 128.43, 126.34, 122.50, 120.99, 83.79, 73.27, 69.55, 67.71, 66.33, 61.68, 21.54, 20.67, 20.58, 20.49, 10.07
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(400 MHz, CDCl₃), δ
3e	8.38(d, 2H, J=8.6 Hz, ArH), 7.64(d, 2H, J=8.6 Hz, ArH), 5.35(d, 1H, J_H1'-H2'=9.1 Hz, H1'), 5.26—5.15(m, 3H, H2', H3', H4'), 4.32(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=5.1 Hz, H6″), 4.24(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=2.0 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=5.1 Hz, J_H5'-H6'=2.1 Hz, H5'), 2.13, 2.08, 2.06, 2.04(4s, 12H, 4CH₃CO)	170.38, 169.97, 169.76, 169.72, 162.70, 155.77, 144.66, 135.54, 129.81, 129.74, 128.43, 128.03, 124.58, 82.52, 75.69, 72.97, 69.73, 68.15, 62.20, 20.90, 20.83, 20.78, 20.70
3f	8.43(d, 1H, J=7.6 Hz, ArH), 8.03(d, 1H, J=8.0 Hz, ArH), 7.57(t, 1H, J=7.6 Hz, ArH), 7.50(t, 1H, J=7.5 Hz, ArH), 5.32—5.12(m, 4H, H1', H2', H3', H4'), 4.29(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.8 Hz, H6″), 4.16(dd, 1H, J_H6'-H6″=12.6 Hz, J_H6'-H5'=1.7 Hz, H6'), 3.86(ddd, 1H, J_H5'-H4'=12.0 Hz, J_H5'-H6″=4.7 Hz, J_H5'-H6'=1.9 Hz, H5'), 2.06, 2.04, 2.03, 2.01(4s, 12H, 4CH₃CO)	170.48, 169.94, 169.24, 168.91, 161.84, 154.69, 145.08, 133.80, 132.09, 130.91, 128.81, 127.09, 124.50, 83.67, 73.23, 69.43, 67.57, 65.54, 61.54, 20.82, 20.69, 20.57, 20.48
3g	5.33(m, 1H, H1'), 5.17(m, 3H, H2', H3', H4'), 4.34(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.23(dd, 1H, J_H6'-H6″=12.6 Hz, J_H6'-H5'=2.0 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.1 Hz, H5'), 2.78(s, 1H, CH₃), 2.13, 2.12, 2.07, 2.05(4s, 12H, 4CH₃CO)	170.40, 169.94, 169.72, 169.68, 161.41, 153.80, 144.39, 82.60, 75.62, 72.92, 69.79, 68.07, 62.13, 20.99, 20.81, 20.74, 20.69, 10.27
3h	5.33(t, 1H, J_H1'-H2'=6.8 Hz, H1'), 5.19—5.13(m, 3H, H2', H3', H4'), 4.32(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.22(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=1.8 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 3.12(dd, 2H, J₁=15.1 Hz, J₂=7.6 Hz, CH₂), 2.12, 2.10, 2.07, 2.04(4s, 12H, 4CH₃CO), 1.46(t, 3H, J=7.6 Hz, CH₃)	170.43, 169.95, 169.22, 169.17, 160.53, 154.24, 140.47, 83.73, 73.24, 73.12, 69.53, 67.60, 61.61, 20.78, 20.68, 20.54, 20.51, 18.75, 11.09
3i	5.30(t, 1H, J_H1'-H2'=9.0 Hz, H1'), 5.17—5.11(m, 3H, H2', H3', H4'), 4.29(dd, 1H, J_H6″-H6=12.7 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.18(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=1.7 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.6 Hz, J_H5'-H6'=1.9 Hz, H5'), 3.04(t, 2H, J=7.5 Hz, CH₂), 2.08, 2.06, 2.03, 2.00(4s, 12H, 4CH₃CO), 1.88(m, 2H, CH₂), 1.02(t, 3H, J=7.4 Hz, CH₃)	170.44, 169.93, 169.22, 169.16, 160.83, 153.60, 148.04, 83.67, 73.22, 69.51, 67.58, 63.67, 61.57, 29.62, 26.82, 20.74, 20.52, 20.49, 20.21, 13.70
3j	5.28(t, 1H, J_H1'-H2'=7.0 Hz, H1'), 5.15-5.09(m, 3H, H2', H3', H4'), 4.28(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.17(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=1.9 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 3.03(t, 2H, J=7.6 Hz, CH₂), 2.07, 2.05, 2.02, 2.00(4s, 12H, 4CH₃CO), 1.83(m, 2H, CH₂), 1.40—1.19(m, 8H, CH₂CH₂CH₂CH₂), 0.84(t, 3H, J=6.7 Hz, CH₃)	170.37, 169.89, 169.18, 169.09, 160.76, 153.55, 148.21, 83.64, 73.22, 69.53, 67.61, 61.57, 58.16, 31.57, 29.00, 28.73, 26.62, 24.89, 22.52, 20.78, 20.67, 20.46, 20.42, 13.98

Table 3 1H NMR and 13C NMR data of intermediate 2b and target compounds 3a—3j

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(400 MHz, CDCl₃), δ
2b	13.8(s, 1H, SH), 11.06(s, 1H, OH), 8.41(d, 1H, J=6.7 Hz, ArH), 7.49(t, 1H, J=6.3 Hz, ArH), 7.12(t, 2H, J=6.3 Hz, ArH)	157.02, 155.98, 155.32, 134.09, 132.41, 129.14, 128.68, 119.89, 116.93
3a	8.32(d, 2H, J=7.12 Hz, ArH), 7.55(m, 3H, ArH) 5.36(m, 1H, H1'), 5.24(m, 2H, H2, H3'), 5.18(t, 1H, $J H 4' - H 5'$ =9.8 Hz, J_H4'-H3'=9.6 Hz, H4'), 4.31(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=5.1 Hz, H6″), 4.23(dd, 1H, J_H6'-H6″=12.4 Hz, J_H6'-H5'=2.1 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.4 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 2.13, 2.08, 2.05, 2.04(4s, 12H, 4CH₃CO)	170.48, 170.16, 169.96, 169.27, 161.47, 154.76, 146.32, 130.62, 128.99, 128.65, 126.44, 125.70, 125.58, 83.73, 73.23, 69.70, 69.51, 67.68, 61.67, 20.68, 20.63, 20.55, 20.51
3b	10.97(s, 1H, OH), 7.94(d, 1H, J=7.7 Hz, ArH), 7.36(t, 1H, J=7.6 Hz, ArH), 7.02(d, 1H, J=8.2 Hz, ArH), 6.97(t, 1H, J=7.6 Hz, ArH), 5.65(d, 1H, J_H1'-H2'=10.2 Hz, H1'), 5.46(t, 1H, $J H 2' - H 1'$ =J_H2'-H3'=9.4 Hz, H2'), 5.08(t, 1H, J_H3'-H4'=J_H3'-H2'=9.7 Hz, H3'), 4.96(t, 1H, J_H4'-H5'=J_H4'-H3'=9.5 Hz, H4'), 4.23(m, 2H, H6″, H6'), 3.99(ddd, 1H, J_H5'-H4'=10.7 Hz, $J H 5' - H 6 ″$ =4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 2.00, 1.99, 1.95, 1.93(4s, 12H, 4CH₃CO)	170.41, 169.94, 169.73, 169.57, 156.28, 155.14, 153.55, 132.35, 127.93, 120.08, 119.92, 117.22, 112.48, 82.63, 75.26, 73.42, 70.34, 68.43, 62.20, 21.49, 20.91, 20.80, 20.72
3c	10.13(s, 1H, OH), 8.04(d, 2H, J=8.7 Hz, ArH), 6.97(d, 2H, J=8.7 Hz, ArH), 5.76(d, 1H, J_H1'-H2'=10.0 Hz, H1'), 5.48(t, 1H, J_H2'-H1'=J_H2'-H3'=9.4 Hz, H2'), 5.14(t, 1H, J_H3'-H4'=J_H3'-H2'=9.7 Hz, H3'), 5.07(t, 1H, J_H4'-H5'=J_H4'-H3'=9.7 Hz, H4'), 4.21(m, 3H, H6″, H6', H5'), 2.09, 2.07, 2.02, 1.96(4s, 12H, 4CH₃CO)	170.38, 169.95, 169.75, 169.71, 159.98, 154.62, 145.81, 132.50, 128.17, 124.43, 120.09, 116.49, 116.43, 82.52, 75.65, 72.94, 69.74, 68.17, 62.17, 20.90, 20.83, 20.79, 20.71
3d	8.19(d, 2H, J=8.0 Hz, ArH), 7.36(d, 2H, J=8.0 Hz, ArH), 5.36(d, 1H, J_H1'-H2'=8.6 Hz, H1'), 5.24(m, 2H, H2', H3'), 5.18(t, 1H, J_H4'-H5'=J_H4'-H3'=9.7 Hz, H4'), 4.32(dd, 1H, J_H6″-H6'=12.5 Hz, J_H6″-H5'=5.1 Hz, H6″), 4.22(dd, 1H, J_H6'-H6″=11.9 Hz, J_H6'-H5'=2.0 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=5.1 Hz, J_H5'-H6'=2.0 Hz, H5'), 2.45(s, 3H, CH₃), 2.13, 2.08, 2.05, 2.04(4s, 12H, 4CH₃CO)	170.46, 169.94, 169.38, 169.24, 161.06, 154.42, 146.48, 140.91, 129.65, 128.43, 126.34, 122.50, 120.99, 83.79, 73.27, 69.55, 67.71, 66.33, 61.68, 21.54, 20.67, 20.58, 20.49, 10.07
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(400 MHz, CDCl₃), δ
3e	8.38(d, 2H, J=8.6 Hz, ArH), 7.64(d, 2H, J=8.6 Hz, ArH), 5.35(d, 1H, J_H1'-H2'=9.1 Hz, H1'), 5.26—5.15(m, 3H, H2', H3', H4'), 4.32(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=5.1 Hz, H6″), 4.24(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=2.0 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=5.1 Hz, J_H5'-H6'=2.1 Hz, H5'), 2.13, 2.08, 2.06, 2.04(4s, 12H, 4CH₃CO)	170.38, 169.97, 169.76, 169.72, 162.70, 155.77, 144.66, 135.54, 129.81, 129.74, 128.43, 128.03, 124.58, 82.52, 75.69, 72.97, 69.73, 68.15, 62.20, 20.90, 20.83, 20.78, 20.70
3f	8.43(d, 1H, J=7.6 Hz, ArH), 8.03(d, 1H, J=8.0 Hz, ArH), 7.57(t, 1H, J=7.6 Hz, ArH), 7.50(t, 1H, J=7.5 Hz, ArH), 5.32—5.12(m, 4H, H1', H2', H3', H4'), 4.29(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.8 Hz, H6″), 4.16(dd, 1H, J_H6'-H6″=12.6 Hz, J_H6'-H5'=1.7 Hz, H6'), 3.86(ddd, 1H, J_H5'-H4'=12.0 Hz, J_H5'-H6″=4.7 Hz, J_H5'-H6'=1.9 Hz, H5'), 2.06, 2.04, 2.03, 2.01(4s, 12H, 4CH₃CO)	170.48, 169.94, 169.24, 168.91, 161.84, 154.69, 145.08, 133.80, 132.09, 130.91, 128.81, 127.09, 124.50, 83.67, 73.23, 69.43, 67.57, 65.54, 61.54, 20.82, 20.69, 20.57, 20.48
3g	5.33(m, 1H, H1'), 5.17(m, 3H, H2', H3', H4'), 4.34(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.23(dd, 1H, J_H6'-H6″=12.6 Hz, J_H6'-H5'=2.0 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.1 Hz, H5'), 2.78(s, 1H, CH₃), 2.13, 2.12, 2.07, 2.05(4s, 12H, 4CH₃CO)	170.40, 169.94, 169.72, 169.68, 161.41, 153.80, 144.39, 82.60, 75.62, 72.92, 69.79, 68.07, 62.13, 20.99, 20.81, 20.74, 20.69, 10.27
3h	5.33(t, 1H, J_H1'-H2'=6.8 Hz, H1'), 5.19—5.13(m, 3H, H2', H3', H4'), 4.32(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.22(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=1.8 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 3.12(dd, 2H, J₁=15.1 Hz, J₂=7.6 Hz, CH₂), 2.12, 2.10, 2.07, 2.04(4s, 12H, 4CH₃CO), 1.46(t, 3H, J=7.6 Hz, CH₃)	170.43, 169.95, 169.22, 169.17, 160.53, 154.24, 140.47, 83.73, 73.24, 73.12, 69.53, 67.60, 61.61, 20.78, 20.68, 20.54, 20.51, 18.75, 11.09
3i	5.30(t, 1H, J_H1'-H2'=9.0 Hz, H1'), 5.17—5.11(m, 3H, H2', H3', H4'), 4.29(dd, 1H, J_H6″-H6=12.7 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.18(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=1.7 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.6 Hz, J_H5'-H6'=1.9 Hz, H5'), 3.04(t, 2H, J=7.5 Hz, CH₂), 2.08, 2.06, 2.03, 2.00(4s, 12H, 4CH₃CO), 1.88(m, 2H, CH₂), 1.02(t, 3H, J=7.4 Hz, CH₃)	170.44, 169.93, 169.22, 169.16, 160.83, 153.60, 148.04, 83.67, 73.22, 69.51, 67.58, 63.67, 61.57, 29.62, 26.82, 20.74, 20.52, 20.49, 20.21, 13.70
3j	5.28(t, 1H, J_H1'-H2'=7.0 Hz, H1'), 5.15-5.09(m, 3H, H2', H3', H4'), 4.28(dd, 1H, J_H6″-H6'=12.6 Hz, J_H6″-H5'=4.9 Hz, H6″), 4.17(dd, 1H, J_H6'-H6″=12.5 Hz, J_H6'-H5'=1.9 Hz, H6'), 3.91(ddd, 1H, J_H5'-H4'=10.0 Hz, J_H5'-H6″=4.8 Hz, J_H5'-H6'=2.0 Hz, H5'), 3.03(t, 2H, J=7.6 Hz, CH₂), 2.07, 2.05, 2.02, 2.00(4s, 12H, 4CH₃CO), 1.83(m, 2H, CH₂), 1.40—1.19(m, 8H, CH₂CH₂CH₂CH₂), 0.84(t, 3H, J=6.7 Hz, CH₃)	170.37, 169.89, 169.18, 169.09, 160.76, 153.55, 148.21, 83.64, 73.22, 69.53, 67.61, 61.57, 58.16, 31.57, 29.00, 28.73, 26.62, 24.89, 22.52, 20.78, 20.67, 20.46, 20.42, 13.98

Scheme 2 Possible reaction mechanism of compound 2a

Table 4 Antibacterial activity data of compounds 3a—3j

Compd.	Minimal inhibitory concentration/(μg·mL^-1)
Compd.	Bacillus subtilis	Staphylococcus aureus	Escherichia coli	Monilia albican
3a	64	64	128	8
3b	64	32	64	4
3c	32	16	32	4
3d	64	32	64	8
3e	64	32	32	8
3f	64	64	128	4
3g	64	64	64	4
3h	64	64	128	4
3i	128	64	128	16
3j	64	128	64	32
Triclosan	16	4	2	32
Fluconazole	32	16	128	2

Fig.1 Docking model of compounds 3c, 3i and triclosan within the FabⅠ

Fig.2 Binding modes of triclosan(A), compounds 3c(B) and 3i(C) with FabⅠ Bond length units are in nm.

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