Synthesis, Antibacterial Activity and Molecular Simulation with FabⅠ of a Series of Novel 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazoles†

doi:10.7503/cjcu20140907

Abstract

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

CLC Number:

O626.26

TrendMD:

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^†[J]. Chem. J. Chinese Universities, 2015, 36(3): 469.

Figures/Tables 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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