Synthesis, Antifungal Activity and Structure-activity Relationship of -Fluorophenyl-2,3-dihydro-1,5-benzothiazepines Derivatives†

doi:10.7503/cjcu20140875

Abstract

Abstract:

Twenty-six 4-fluoropheny-2,3-dihydro-l,5-benzothiazepine derivatives 2a—2z were synthesized and characterized by ¹H NMR, ¹³C NMR, IR and high resolution mass spectrum(HRMS). The antifungal activities of those compounds were screened using the disk diffusion method against C. albicans and C. neoformans. The results showed that benzothiazepines 2a—2f had high antifungal activities against C. neoformans, while all of the benzothiazepines 2a—2z were almost inactive against C. albicans. Furthermore, the 1,5-benzothiazepines 2a—2f, which had high antifungal activities, were subjected to further pharmacological evaluation, including minimum inhibitory concentration(MIC, MIC₈₀) and minimum fungicidal concentration(MFC) against C. neoformans. The results revealed that the MIC and MFC values for the above compounds were much lower than those of fluconazole. In order to study the structural features responsible for the antifungal activity of compounds 2a—2f, four series of analogues 3a—3f, 4a—4f, 5a—5f and 6a—6c were synthesized and tested for their antifungal activities against C. neoformans. The results suggested that the sulfur atoms, C=N structure on the seven-membered ring and the methoxycarbonyl/ethoxycarbonyl group at the 2 position are essential for antifungal activity.

Key words: 1,5-Benzothiazepine, Antifungal activity, Structure-activity relationship

CLC Number:

O626

TrendMD:

ZHANG Jing, MU Boshuai, WU Meng, BIAN Yanqing, LI Yuan. Synthesis, Antifungal Activity and Structure-activity Relationship of -Fluorophenyl-2,3-dihydro-1,5-benzothiazepines Derivatives^†[J]. Chem. J. Chinese Universities, 2015, 36(4): 687.

Figures/Tables 9

Scheme 1 Synthesis routes of 1,5-benzothiazepines 2—5 a. R=CH3, Ar=2,3-F2C6H3; b. R=CH3, Ar=2,5-F2C6H3; c. R=CH3, Ar=3,4-F2C6H3; d. R=C2H5, Ar=2,3-F2C6H3; e. R=C2H5, Ar=2,5-F2C6H3; f. R=C2H5, Ar=3,4-F2C6H3; g. R=CH3, Ar=2,6-F2C6H3; h. R=CH3, Ar=3,5-F2C6H3; i. R=C2H5, Ar=2,6-F2C6H3; j. R=C2H5, Ar=3,5-F2C6H3; k. R=CH3, Ar=2,3,4-F3C6H2; l. R=CH3, Ar=2,3,6-F3C6H2; m. R=CH3, Ar=2,4,5-F3C6H2; n. R=CH3, Ar=2,4,6-F3C6H2; o. R=CH3, Ar=3,4,5-F3C6H2; p. R=C2H5, Ar=2,3,4-F3C6H2; q. R=C2H5, Ar=2,3,6-F3C6H2; r. R=C2H5, Ar=2,4,5-F3C6H2; s. R=C2H5, Ar=2,4,6-F3C6H2; t. R=C2H5, Ar=3,4,5-F3C6H2; u. R=CH3, Ar=3-CF3-C6H4; v. R=CH3, Ar=4-CF3-C6H4; w. R=CH3, Ar=3,5-bis(CF3)-C6H3; x. R=C2H5, Ar=3-CF3-C6H4; y. R=C2H5, Ar=4-CF3-C6H4; z. R=C2H5, Ar=3,5-bis(CF3)-C6H3

Table 1 Yields, melting points, HRMS and IR data for compounds 2

Compd.	Isolated yield(%)	m.p./℃	HRMS(calcd., [M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
2a	85.0	106—108	334.0708(334.0707)	1736.0, 1610.6
2b	80.0	111—113	334.0705(334.0707)	1732.1, 1608.9
2c	86.5	98—100	334.0708(334.0707)	1728.3, 1620.0
2d	87.0	102—104	348.0860(348.0864)	1724.4, 1618.3
2e	90.2	99—101	348.0858(348.0864)	1705.1, 1600.9
2f	86.8	103—105	348.0860(348.0864)	1728.3, 1600.0
2g	82.5	96—97	334.0708(334.0707)	1732.1, 1618.3
2h	89.3	87—89	334.0708(334.0707)	1726.4, 1610.6
2i	86.0	101—102	348.0860(348.0864)	1728.3, 1629.9
Compd.	Isolated yield(%)	m.p./℃	HRMS(calcd., [M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
2j	91.0	105—106	348.0864(348.0864)	1726.3, 1610.9
2k	72.5	96—97	352.0609(352.0613)	1730.1, 1640.5
2l	75.8	78—79	352.0608(352.0613)	1731.2, 1641.0
2m	69.4	106—107	352.0609(352.0613)	1732.9, 1641.3
2n	80.0	108—110	352.0614(352.0613)	1732.1, 1641.5
2o	87.3	86—87	352.0609(352.0613)	1724.4, 1601.5
2p	69.2	106—107	366.0767(366.0770)	1730.1, 1640.5
2q	68.5	98—99	366.0765(366.0770)	1731.2, 1641.0
2r	75.3	91—93	366.0764(366.0770)	1732.9, 1641.3
2s	78.7	101—103	366.0770(366.0770)	1707.1, 1618.3
2t	82.8	91—93	366.0765(366.0770)	1716.7, 1601.5
2u	85.7	76—77	366.0766(366.0770)	1724.4, 1676.2
2v	88.9	86—87	366.0768(366.0770)	1716.7, 1610.6
2w	89.2	80—81	434.0636(434.0644)	1728.6, 1620.3
2x	81.3	79—81	380.0923(380.0926)	1720.6, 1622.2
2y	85.3	86—87	380.0924(380.0926)	1708.9, 1618.3
2z	80.2	80—82	448.0792(448.0800)	1728.9, 1619.3

Table 1 Yields, melting points, HRMS and IR data for compounds 2

Compd.	Isolated yield(%)	m.p./℃	HRMS(calcd., [M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
2a	85.0	106—108	334.0708(334.0707)	1736.0, 1610.6
2b	80.0	111—113	334.0705(334.0707)	1732.1, 1608.9
2c	86.5	98—100	334.0708(334.0707)	1728.3, 1620.0
2d	87.0	102—104	348.0860(348.0864)	1724.4, 1618.3
2e	90.2	99—101	348.0858(348.0864)	1705.1, 1600.9
2f	86.8	103—105	348.0860(348.0864)	1728.3, 1600.0
2g	82.5	96—97	334.0708(334.0707)	1732.1, 1618.3
2h	89.3	87—89	334.0708(334.0707)	1726.4, 1610.6
2i	86.0	101—102	348.0860(348.0864)	1728.3, 1629.9
Compd.	Isolated yield(%)	m.p./℃	HRMS(calcd., [M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
2j	91.0	105—106	348.0864(348.0864)	1726.3, 1610.9
2k	72.5	96—97	352.0609(352.0613)	1730.1, 1640.5
2l	75.8	78—79	352.0608(352.0613)	1731.2, 1641.0
2m	69.4	106—107	352.0609(352.0613)	1732.9, 1641.3
2n	80.0	108—110	352.0614(352.0613)	1732.1, 1641.5
2o	87.3	86—87	352.0609(352.0613)	1724.4, 1601.5
2p	69.2	106—107	366.0767(366.0770)	1730.1, 1640.5
2q	68.5	98—99	366.0765(366.0770)	1731.2, 1641.0
2r	75.3	91—93	366.0764(366.0770)	1732.9, 1641.3
2s	78.7	101—103	366.0770(366.0770)	1707.1, 1618.3
2t	82.8	91—93	366.0765(366.0770)	1716.7, 1601.5
2u	85.7	76—77	366.0766(366.0770)	1724.4, 1676.2
2v	88.9	86—87	366.0768(366.0770)	1716.7, 1610.6
2w	89.2	80—81	434.0636(434.0644)	1728.6, 1620.3
2x	81.3	79—81	380.0923(380.0926)	1720.6, 1622.2
2y	85.3	86—87	380.0924(380.0926)	1708.9, 1618.3
2z	80.2	80—82	448.0792(448.0800)	1728.9, 1619.3

Table 2 1H NMR and 13C NMR data for compounds 2

Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
2a	7.10—7.98(m, 7H, PhH), 4.51(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.75(s, 3H, OCH₃), 3.17(t, 1H, CH₂, J=12.5 Hz), 3.08(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.78, 166.73, 151.42, 151.38(dd, J_C—F=246.62, 12.62 Hz), 149.39(dd, J_C—F=251.62, 13.37 Hz), 135.56, 130.59, 129.02(d, J_C—F=8.12 Hz), 125.95, 125.23(d, J_C—F=1.62 Hz), 124.98, 124.41(d, J_C—F=6.87 Hz), 121.44, 119.34(d, J_C—F=16.75 Hz), 55.48, 52.67, 34.90
2b	7.11—7.82(m, 7H, PhH), 4.51(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.75(s, 3H, OCH₃), 3.09—3.16(m, 2H, CH₂)	170.83, 166.50, 159.12(dd, J_C—F=243.75, 3.37 Hz), 157.17(dd, J_C—F=247.00, 3.87 Hz), 151.38, 135.54, 130.57, 128.10(dd, J_C—F=13.62, 7.25 Hz), 125.93, 124.99, 121.52, 119.15(dd, J_C—F=24.62, 9.50 Hz), 117.77(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 55.51, 52.64, 34.70
2c	7.00—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.73(s, 3H, OCH₃), 3.23(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz)	170.62, 163.86, 160.36(dd, J_C—F=250.25, 6.75 Hz), 151.42, 135.49, 131.12(t, J_C—F=10.13 Hz), 130.48, 126.14, 125.39, 121.50, 118.15(t, J_C—F=18.12 Hz), 112.11(dd, J_C—F=20.25, 4.87 Hz), 55.69, 52.64, 35.89
2d	7.12—7.82(m, 7H, PhH), 4.48(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.20(q, 2H, OCH₂, J=7.0 Hz), 3.17(t, 1H, CH₂, J=12.5 Hz), 3.07(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.29(t, 3H, CH₃, J=7.5 Hz)	170.22, 166.90, 151.45, 151.36(dd, J_C—F=246.62, 12.62 Hz), 149.37(dd, J_C—F=251.62, 13.37 Hz), 135.58, 130.54, 129.10(d, J_C—F=8.25 Hz), 125.90, 125.23(d, J_C—F=1.50 Hz), 124.93, 124.39(d, J_C—F=6.87 Hz), 121.55, 119.29(d, J_C—F=17.12 Hz), 61.61, 55.77, 34.87, 14.07
2e	7.12—7.83(m, 7H, PhH), 4.51(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.21(q, 2H, OCH₂, J=7.0 Hz), 3.10—3.18(m, 2H, CH₂), 1.29(t, 3H, CH₃, J=7.0 Hz)	170.27, 166.66, 159.12(dd, J_C—F=243.75, 3.37 Hz), 157.17(dd, J_C—F=247.00, 3.87 Hz), 151.41, 135.57, 130.52, 128.17(dd, J_C—F=13.62, 7.25 Hz), 125.87, 124.94, 121.62, 119.15(dd, J_C—F=24.62, 9.50 Hz), 117.77(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 61.57, 55.79, 34.70, 14.08
2f	7.02—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.19(q, 2H, OCH₂, J=7.0 Hz), 3.25(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz), 1.28(t, 3H, CH₃, J=7.0 Hz)	170.04, 163.99, 160.33(dd, J_C—F=250.37, 6.87 Hz), 151.48, 135.50, 131.11(t, J_C—F=10.13 Hz), 130.43, 126.06, 125.22, 121.62, 118.21(t, J_C—F=18.25 Hz), 112.08(dd, J_C—F=20.50, 5.12 Hz), 61.58, 55.98, 35.88, 14.04
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
2g	7.00—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.73(s, 3H, OCH₃), 3.23(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz)	170.62, 163.86, 160.36(dd, J_C—F=250.25, 6.75 Hz), 151.42, 135.49, 131.12(t, J_C—F=10.13 Hz), 130.48, 126.14, 125.39, 121.50, 118.15(t, J_C—F=18.12 Hz), 112.11(dd, J_C—F=20.25, 4.87 Hz), 55.69, 52.64, 35.89
2h	6.95—7.58(m, 7H, PhH), 4.35(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.78(s, 3H, OCH₃), 3.07—3.16(m, 2H, CH₂)	170.54, 166.78, 163.31(dd, J_C—F=247.25, 12.62 Hz), 151.97, 140.87(t, J_C—F=8.87 Hz), 135.54, 130.66, 125.92, 125.05, 120.96, 110.34(dd, J_C—F=20.62, 6.12 Hz), 106.44(t, J_C—F=25.75 Hz), 55.82, 52.76, 31.54
2i	7.02—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.19(q, 2H, OCH₂, J=7.0 Hz), 3.25(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz), 1.28(t, 3H, CH₃, J=7.0 Hz)	170.04, 163.99, 160.33(dd, J_C—F=250.37, 6.87 Hz), 151.48, 135.50, 131.11(t, J_C—F=10.13 Hz), 130.43, 126.06, 125.22, 121.62, 118.21(t, J_C—F=18.25 Hz), 112.08(dd, J_C—F=20.50, 5.12 Hz), 61.58, 55.98, 35.88, 14.04
2j	6.95—7.59(m, 7H, PhH), 4.33(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.06—3.17(m, 2H, CH₂), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.54, 166.89, 163.28(dd, J_C—F=247.63, 12.25 Hz), 152.02, 140.95(t, J_C—F=8.62 Hz), 135.56, 130.60, 125.84, 124.98, 121.06, 110.34(dd, J_C—F=20.25, 6.62 Hz), 106.38(t, J_C—F=25.37 Hz), 61.77, 56.09, 31.52, 14.08
2k	7.09—7.90(m, 6H, PhH), 4.51(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.78(s, 3H, OCH₃), 3.18(t, 1H, CH₂, J=13.5 Hz), 3.07(dd, 1H, CH₂, J=13.0, 5.5 Hz)	165.95, 160.96, 146.51, 142.76, 140.79, 139.17, 130.83, 125.88, 121.27, 120.19, 119.61, 113.61, 108.03, 53.67, 50.70, 30.00
2l	6.96—7.62(m, 6H, PhH), 4.52(dd, 1H, SCH, J=11.5, 5.5 Hz), 3.76(s, 3H, OCH₃), 3.26(t, 1H, CH₂, J=12.0 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.49, 162.93, 162.99, 162.08, 161.82, 159.81, 151.19, 135.50, 130.53, 126.22, 125.22, 121.42, 114.83, 101.02, 55.80, 52.69, 35.78
2m	7.02—8.03(m, 6H, PhH), 4.51(dd, 1H, SCH, J=11.5, 5.5 Hz), 3.78(s, 3H, OCH₃), 3.15(t, 1H, CH₂, J=12.0 Hz), 3.08(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.75, 165.36, 154.56, 152.02, 151.23, 149.70, 135.57, 130.63, 125.99, 124.97, 123.25, 121.50, 108.30, 55.48, 52.67, 34.70
2n	6.77—7.59(m, 6H, PhH), 4.47(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.73(s, 3H, OCH₃), 3.21(t, 1H, CH₂, J=12.5 Hz), 2.82(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.75, 165.36, 162.99, 162.08, 161.82, 159.81, 151.27, 135.50, 130.53, 126.22, 125.22, 121.42, 114.83, 101.02, 55.75, 52.64, 35.81
2o	7.12—7.72(m, 6H, PhH), 4.34(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.78(s, 3H, OCH₃), 3.04—3.16(m, 2H, CH₂)	170.46, 165.75, 152.42, 151.91, 150.42, 135.56, 140.87, 130.70, 125.96, 125.04, 120.85, 111.69, 55.75, 52.81, 31.15
2p	7.09—7.89(m, 6H, PhH), 4.47(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.23(q, 2H, OCH₂, J=7.0 Hz), 3.19(t, 1H, CH₂, J=13.5 Hz), 3.06(dd, 1H, CH₂, J=13.0, 5.5 Hz)	165.95, 160.96, 146.51, 142.76, 140.79, 139.17, 130.83, 125.88, 121.27, 120.19, 119.61, 113.61, 108.03, 53.67, 50.70, 30.00
2q	6.96—7.61(m, 6H, PhH), 4.52(dd, 1H, SCH, J=11.5, 5.5 Hz), 4.20(q, 2H, OCH₂, J=7.0 Hz), 3.26(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.5 Hz)	169.94, 163.04, 146.51, 142.76, 140.79, 139.17, 130.83, 125.88, 121.27, 120.19, 119.61, 113.61, 108.03, 61.66, 56.10, 35.79, 14.03
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
2r	6.78—7.59(m, 6H, PhH), 4.45(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.18(q, 2H, OCH₂, J=7.0 Hz), 3.22(t, 1H, CH₂, J=12.5 Hz), 2.82(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.27(t, 3H, CH₃, J=7.0 Hz)	169.97, 163.24, 161.64, 160.83, 151.17, 135.55, 130.50, 126.24, 125.22, 121.61, 114.80, 101.04, 61.66, 56.05, 35.85, 14.04
2s	6.78—7.59(m, 6H, PhH), 4.45(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.18(q, 2H, OCH₂, J=7.0 Hz), 3.22(t, 1H, CH₂, J=12.5 Hz), 2.82(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.27(t, 3H, CH₃, J=7.0 Hz)	169.97, 163.24, 161.64, 160.83, 151.17, 135.55, 130.50, 126.24, 125.22, 121.61, 114.80, 101.04, 61.66, 56.05, 35.85, 14.04
2t	7.12—7.73(m, 6H, PhH), 4.31(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.13(t, 1H, CH₂, J=12.5 Hz), 3.05(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.54, 166.89, 163.28(dd, J_C—F=247.63, 12.25 Hz), 152.02, 140.95(t, J_C—F=8.62 Hz), 135.56, 130.60, 125.84, 124.98, 121.06, 110.34(dd, J_C—F=20.25, 6.62 Hz), 106.38(t, J_C—F=25.37 Hz), 61.77, 56.09, 31.52, 14.08
2u	7.14—8.34(m, 8H, PhH), 4.40(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.80(s, 3H, OCH₃), 3.17—3.25(m, 2H, CH₂)	170.60, 167.66, 152.25, 138.33, 135.52, 131.47, 130.64, 130.49, 129.35, 127.71, 125.76, 125.03, 124.12, 120.93, 55.83, 52.73, 31.45
2v	7.14—8.17(m, 8H, PhH), 4.39(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.80(s, 3H, OCH₃), 3.17—3.25(m, 2H, CH₂)	170.08, 168.17, 152.10, 140.70, 135.57, 132.81, 130.61, 127.74, 125.84, 125.75, 125.04, 122.80, 121.10, 61.16, 56.10, 31.69
2w	7.15—8.48(m, 7H, PhH), 4.41(dd, 1H, SCH, J=12.0, J=6.0 Hz), 3.79(s, 3H, OCH₃), 3.25(t, 1H, CH₂, J=12.0 Hz), 3.18(dd, 1H, CH₂, J=13.5, 6.0 Hz)	170.40, 166.25, 151.78, 139.64, 135.60, 132.29, 130.77, 127.32, 126.21, 125.14, 124.47, 124.25, 122.08, 120.09, 55.89, 52.80, 31.34
2x	7.12—8.32(m, 8H, PhH), 4.35(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.27(q, 2H, OCH₂, J=7.0 Hz), 3.14—3.22(m, 2H, CH₂), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.60, 167.66, 152.25, 138.33, 135.52, 131.47, 130.64, 130.49, 129.35, 127.71, 125.76, 125.03, 124.12, 120.93, 55.83, 52.73, 31.45
2y	7.14—8.17(m, 8H, PhH), 4.34(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.14—3.23(m, 2H, CH₂), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.08, 168.17, 152.10, 140.70, 135.57, 132.81, 130.61, 127.74, 125.84, 125.75, 125.04, 122.80, 121.10, 61.16, 56.10, 31.69, 14.08
2z	7.17—8.50(m, 7H, PhH), 4.39(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.27(q, 2H, OCH₂, J=7.0 Hz), 3.26(t, 1H, CH₂, J=12.0 Hz), 3.19(dd, 1H, CH₂, J=13.5, 6.0 Hz), 1.30(t, 3H, CH₃, J=7.0 Hz)	169.78, 166.36, 151.83, 139.81, 135.58, 132.32, 130.67, 127.33, 126.11, 125.09, 124.38, 124.25, 122.08, 121.12, 61.84, 56.22, 31.43, 13.99

Table 2 1H NMR and 13C NMR data for compounds 2

Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
2a	7.10—7.98(m, 7H, PhH), 4.51(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.75(s, 3H, OCH₃), 3.17(t, 1H, CH₂, J=12.5 Hz), 3.08(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.78, 166.73, 151.42, 151.38(dd, J_C—F=246.62, 12.62 Hz), 149.39(dd, J_C—F=251.62, 13.37 Hz), 135.56, 130.59, 129.02(d, J_C—F=8.12 Hz), 125.95, 125.23(d, J_C—F=1.62 Hz), 124.98, 124.41(d, J_C—F=6.87 Hz), 121.44, 119.34(d, J_C—F=16.75 Hz), 55.48, 52.67, 34.90
2b	7.11—7.82(m, 7H, PhH), 4.51(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.75(s, 3H, OCH₃), 3.09—3.16(m, 2H, CH₂)	170.83, 166.50, 159.12(dd, J_C—F=243.75, 3.37 Hz), 157.17(dd, J_C—F=247.00, 3.87 Hz), 151.38, 135.54, 130.57, 128.10(dd, J_C—F=13.62, 7.25 Hz), 125.93, 124.99, 121.52, 119.15(dd, J_C—F=24.62, 9.50 Hz), 117.77(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 55.51, 52.64, 34.70
2c	7.00—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.73(s, 3H, OCH₃), 3.23(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz)	170.62, 163.86, 160.36(dd, J_C—F=250.25, 6.75 Hz), 151.42, 135.49, 131.12(t, J_C—F=10.13 Hz), 130.48, 126.14, 125.39, 121.50, 118.15(t, J_C—F=18.12 Hz), 112.11(dd, J_C—F=20.25, 4.87 Hz), 55.69, 52.64, 35.89
2d	7.12—7.82(m, 7H, PhH), 4.48(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.20(q, 2H, OCH₂, J=7.0 Hz), 3.17(t, 1H, CH₂, J=12.5 Hz), 3.07(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.29(t, 3H, CH₃, J=7.5 Hz)	170.22, 166.90, 151.45, 151.36(dd, J_C—F=246.62, 12.62 Hz), 149.37(dd, J_C—F=251.62, 13.37 Hz), 135.58, 130.54, 129.10(d, J_C—F=8.25 Hz), 125.90, 125.23(d, J_C—F=1.50 Hz), 124.93, 124.39(d, J_C—F=6.87 Hz), 121.55, 119.29(d, J_C—F=17.12 Hz), 61.61, 55.77, 34.87, 14.07
2e	7.12—7.83(m, 7H, PhH), 4.51(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.21(q, 2H, OCH₂, J=7.0 Hz), 3.10—3.18(m, 2H, CH₂), 1.29(t, 3H, CH₃, J=7.0 Hz)	170.27, 166.66, 159.12(dd, J_C—F=243.75, 3.37 Hz), 157.17(dd, J_C—F=247.00, 3.87 Hz), 151.41, 135.57, 130.52, 128.17(dd, J_C—F=13.62, 7.25 Hz), 125.87, 124.94, 121.62, 119.15(dd, J_C—F=24.62, 9.50 Hz), 117.77(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 61.57, 55.79, 34.70, 14.08
2f	7.02—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.19(q, 2H, OCH₂, J=7.0 Hz), 3.25(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz), 1.28(t, 3H, CH₃, J=7.0 Hz)	170.04, 163.99, 160.33(dd, J_C—F=250.37, 6.87 Hz), 151.48, 135.50, 131.11(t, J_C—F=10.13 Hz), 130.43, 126.06, 125.22, 121.62, 118.21(t, J_C—F=18.25 Hz), 112.08(dd, J_C—F=20.50, 5.12 Hz), 61.58, 55.98, 35.88, 14.04
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
2g	7.00—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.73(s, 3H, OCH₃), 3.23(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz)	170.62, 163.86, 160.36(dd, J_C—F=250.25, 6.75 Hz), 151.42, 135.49, 131.12(t, J_C—F=10.13 Hz), 130.48, 126.14, 125.39, 121.50, 118.15(t, J_C—F=18.12 Hz), 112.11(dd, J_C—F=20.25, 4.87 Hz), 55.69, 52.64, 35.89
2h	6.95—7.58(m, 7H, PhH), 4.35(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.78(s, 3H, OCH₃), 3.07—3.16(m, 2H, CH₂)	170.54, 166.78, 163.31(dd, J_C—F=247.25, 12.62 Hz), 151.97, 140.87(t, J_C—F=8.87 Hz), 135.54, 130.66, 125.92, 125.05, 120.96, 110.34(dd, J_C—F=20.62, 6.12 Hz), 106.44(t, J_C—F=25.75 Hz), 55.82, 52.76, 31.54
2i	7.02—7.60(m, 7H, PhH), 4.49(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.19(q, 2H, OCH₂, J=7.0 Hz), 3.25(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.0 Hz), 1.28(t, 3H, CH₃, J=7.0 Hz)	170.04, 163.99, 160.33(dd, J_C—F=250.37, 6.87 Hz), 151.48, 135.50, 131.11(t, J_C—F=10.13 Hz), 130.43, 126.06, 125.22, 121.62, 118.21(t, J_C—F=18.25 Hz), 112.08(dd, J_C—F=20.50, 5.12 Hz), 61.58, 55.98, 35.88, 14.04
2j	6.95—7.59(m, 7H, PhH), 4.33(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.06—3.17(m, 2H, CH₂), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.54, 166.89, 163.28(dd, J_C—F=247.63, 12.25 Hz), 152.02, 140.95(t, J_C—F=8.62 Hz), 135.56, 130.60, 125.84, 124.98, 121.06, 110.34(dd, J_C—F=20.25, 6.62 Hz), 106.38(t, J_C—F=25.37 Hz), 61.77, 56.09, 31.52, 14.08
2k	7.09—7.90(m, 6H, PhH), 4.51(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.78(s, 3H, OCH₃), 3.18(t, 1H, CH₂, J=13.5 Hz), 3.07(dd, 1H, CH₂, J=13.0, 5.5 Hz)	165.95, 160.96, 146.51, 142.76, 140.79, 139.17, 130.83, 125.88, 121.27, 120.19, 119.61, 113.61, 108.03, 53.67, 50.70, 30.00
2l	6.96—7.62(m, 6H, PhH), 4.52(dd, 1H, SCH, J=11.5, 5.5 Hz), 3.76(s, 3H, OCH₃), 3.26(t, 1H, CH₂, J=12.0 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.49, 162.93, 162.99, 162.08, 161.82, 159.81, 151.19, 135.50, 130.53, 126.22, 125.22, 121.42, 114.83, 101.02, 55.80, 52.69, 35.78
2m	7.02—8.03(m, 6H, PhH), 4.51(dd, 1H, SCH, J=11.5, 5.5 Hz), 3.78(s, 3H, OCH₃), 3.15(t, 1H, CH₂, J=12.0 Hz), 3.08(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.75, 165.36, 154.56, 152.02, 151.23, 149.70, 135.57, 130.63, 125.99, 124.97, 123.25, 121.50, 108.30, 55.48, 52.67, 34.70
2n	6.77—7.59(m, 6H, PhH), 4.47(dd, 1H, SCH, J=12.0, 5.5 Hz), 3.73(s, 3H, OCH₃), 3.21(t, 1H, CH₂, J=12.5 Hz), 2.82(dd, 1H, CH₂, J=13.0, 5.5 Hz)	170.75, 165.36, 162.99, 162.08, 161.82, 159.81, 151.27, 135.50, 130.53, 126.22, 125.22, 121.42, 114.83, 101.02, 55.75, 52.64, 35.81
2o	7.12—7.72(m, 6H, PhH), 4.34(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.78(s, 3H, OCH₃), 3.04—3.16(m, 2H, CH₂)	170.46, 165.75, 152.42, 151.91, 150.42, 135.56, 140.87, 130.70, 125.96, 125.04, 120.85, 111.69, 55.75, 52.81, 31.15
2p	7.09—7.89(m, 6H, PhH), 4.47(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.23(q, 2H, OCH₂, J=7.0 Hz), 3.19(t, 1H, CH₂, J=13.5 Hz), 3.06(dd, 1H, CH₂, J=13.0, 5.5 Hz)	165.95, 160.96, 146.51, 142.76, 140.79, 139.17, 130.83, 125.88, 121.27, 120.19, 119.61, 113.61, 108.03, 53.67, 50.70, 30.00
2q	6.96—7.61(m, 6H, PhH), 4.52(dd, 1H, SCH, J=11.5, 5.5 Hz), 4.20(q, 2H, OCH₂, J=7.0 Hz), 3.26(t, 1H, CH₂, J=12.5 Hz), 2.87(dd, 1H, CH₂, J=13.0, 5.5 Hz)	169.94, 163.04, 146.51, 142.76, 140.79, 139.17, 130.83, 125.88, 121.27, 120.19, 119.61, 113.61, 108.03, 61.66, 56.10, 35.79, 14.03
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
2r	6.78—7.59(m, 6H, PhH), 4.45(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.18(q, 2H, OCH₂, J=7.0 Hz), 3.22(t, 1H, CH₂, J=12.5 Hz), 2.82(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.27(t, 3H, CH₃, J=7.0 Hz)	169.97, 163.24, 161.64, 160.83, 151.17, 135.55, 130.50, 126.24, 125.22, 121.61, 114.80, 101.04, 61.66, 56.05, 35.85, 14.04
2s	6.78—7.59(m, 6H, PhH), 4.45(dd, 1H, SCH, J=12.0, 5.5 Hz), 4.18(q, 2H, OCH₂, J=7.0 Hz), 3.22(t, 1H, CH₂, J=12.5 Hz), 2.82(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.27(t, 3H, CH₃, J=7.0 Hz)	169.97, 163.24, 161.64, 160.83, 151.17, 135.55, 130.50, 126.24, 125.22, 121.61, 114.80, 101.04, 61.66, 56.05, 35.85, 14.04
2t	7.12—7.73(m, 6H, PhH), 4.31(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.13(t, 1H, CH₂, J=12.5 Hz), 3.05(dd, 1H, CH₂, J=13.0, 5.5 Hz), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.54, 166.89, 163.28(dd, J_C—F=247.63, 12.25 Hz), 152.02, 140.95(t, J_C—F=8.62 Hz), 135.56, 130.60, 125.84, 124.98, 121.06, 110.34(dd, J_C—F=20.25, 6.62 Hz), 106.38(t, J_C—F=25.37 Hz), 61.77, 56.09, 31.52, 14.08
2u	7.14—8.34(m, 8H, PhH), 4.40(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.80(s, 3H, OCH₃), 3.17—3.25(m, 2H, CH₂)	170.60, 167.66, 152.25, 138.33, 135.52, 131.47, 130.64, 130.49, 129.35, 127.71, 125.76, 125.03, 124.12, 120.93, 55.83, 52.73, 31.45
2v	7.14—8.17(m, 8H, PhH), 4.39(dd, 1H, SCH, J=12.0, 6.0 Hz), 3.80(s, 3H, OCH₃), 3.17—3.25(m, 2H, CH₂)	170.08, 168.17, 152.10, 140.70, 135.57, 132.81, 130.61, 127.74, 125.84, 125.75, 125.04, 122.80, 121.10, 61.16, 56.10, 31.69
2w	7.15—8.48(m, 7H, PhH), 4.41(dd, 1H, SCH, J=12.0, J=6.0 Hz), 3.79(s, 3H, OCH₃), 3.25(t, 1H, CH₂, J=12.0 Hz), 3.18(dd, 1H, CH₂, J=13.5, 6.0 Hz)	170.40, 166.25, 151.78, 139.64, 135.60, 132.29, 130.77, 127.32, 126.21, 125.14, 124.47, 124.25, 122.08, 120.09, 55.89, 52.80, 31.34
2x	7.12—8.32(m, 8H, PhH), 4.35(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.27(q, 2H, OCH₂, J=7.0 Hz), 3.14—3.22(m, 2H, CH₂), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.60, 167.66, 152.25, 138.33, 135.52, 131.47, 130.64, 130.49, 129.35, 127.71, 125.76, 125.03, 124.12, 120.93, 55.83, 52.73, 31.45
2y	7.14—8.17(m, 8H, PhH), 4.34(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.14—3.23(m, 2H, CH₂), 1.31(t, 3H, CH₃, J=7.0 Hz)	170.08, 168.17, 152.10, 140.70, 135.57, 132.81, 130.61, 127.74, 125.84, 125.75, 125.04, 122.80, 121.10, 61.16, 56.10, 31.69, 14.08
2z	7.17—8.50(m, 7H, PhH), 4.39(dd, 1H, SCH, J=12.0, 6.0 Hz), 4.27(q, 2H, OCH₂, J=7.0 Hz), 3.26(t, 1H, CH₂, J=12.0 Hz), 3.19(dd, 1H, CH₂, J=13.5, 6.0 Hz), 1.30(t, 3H, CH₃, J=7.0 Hz)	169.78, 166.36, 151.83, 139.81, 135.58, 132.32, 130.67, 127.33, 126.11, 125.09, 124.38, 124.25, 122.08, 121.12, 61.84, 56.22, 31.43, 13.99

Scheme 2 Synthesis routes of compounds 6a—6c a. Ar=2,3-F2C6H3; b. Ar=2,5-F2C6H3; c. Ar=3,4-F2C6H3

Table 3 Yields, melting points, HRMS and IR data for compounds 3—6

Compd.	Isolated yield(%)	m.p./℃	HRMS(calcd., [M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
3a	45.2	56—57	318.0938(318.0936)	1734.1, 1610.6
3b	48.3	68—70	318.0938(318.0936)	1747.6, 1610.6
3c	43.7	76—77	318.0937(318.0936)	1726.4, 1616.4
3d	37.6	53—55	332.1093(332.1092)	1722.5, 1622.6
3e	35.9	46—47	332.1094(332.1092)	1736.0, 1628.0
3f	45.5	36—37	332.1091(332.1092)	1734.1, 1618.3
4a	92.1	86—88	317.1093(317.1096)	3327.3, 1743.7, 1612.5
4b	95.3	90—92	317.1093(317.1096)	3356.3, 1745.6, 1618.3
4c	89.8	89—91	317.1093(317.1096)	3362.0, 1741.8, 1601.0
4d	87.9	90—92	331.1249(331.1252)	3365.9, 1726.4, 1618.3
4e	85.9	85—87	331.1248(331.1252)	3373.6, 1736.0, 1610.6
4f	87.7	81—83	331.1250(331.1252)	3375.5, 1732.1, 1612.5
5a	87.9	109—111	336.0864(336.0864)	3391.0, 1718.6
5b	86.8		336.0859(336.0864)	3390.9, 1720.6
5c	89.0	103—105	336.0863(336.0864)	3385.2, 1720.6
5d	85.4	108—110	350.1019(350.1020)	3387.1, 1710.9
5e	88.5		350.1016(350.1020)	3392.9, 1720.6
5f	90.0		350.1016(350.1020)	3388.7, 1710.6
6a	87.3	91—93	276.0652(276.0653)	1608.9
6b	83.5	97—99	276.0656(276.0653)	1612.5
6c	79.2	89—91	276.0651(276.0653)	1610.7

Table 3 Yields, melting points, HRMS and IR data for compounds 3—6

Compd.	Isolated yield(%)	m.p./℃	HRMS(calcd., [M+H]⁺), m/z	IR(KBr), $ν ˙$ /cm^-1
3a	45.2	56—57	318.0938(318.0936)	1734.1, 1610.6
3b	48.3	68—70	318.0938(318.0936)	1747.6, 1610.6
3c	43.7	76—77	318.0937(318.0936)	1726.4, 1616.4
3d	37.6	53—55	332.1093(332.1092)	1722.5, 1622.6
3e	35.9	46—47	332.1094(332.1092)	1736.0, 1628.0
3f	45.5	36—37	332.1091(332.1092)	1734.1, 1618.3
4a	92.1	86—88	317.1093(317.1096)	3327.3, 1743.7, 1612.5
4b	95.3	90—92	317.1093(317.1096)	3356.3, 1745.6, 1618.3
4c	89.8	89—91	317.1093(317.1096)	3362.0, 1741.8, 1601.0
4d	87.9	90—92	331.1249(331.1252)	3365.9, 1726.4, 1618.3
4e	85.9	85—87	331.1248(331.1252)	3373.6, 1736.0, 1610.6
4f	87.7	81—83	331.1250(331.1252)	3375.5, 1732.1, 1612.5
5a	87.9	109—111	336.0864(336.0864)	3391.0, 1718.6
5b	86.8		336.0859(336.0864)	3390.9, 1720.6
5c	89.0	103—105	336.0863(336.0864)	3385.2, 1720.6
5d	85.4	108—110	350.1019(350.1020)	3387.1, 1710.9
5e	88.5		350.1016(350.1020)	3392.9, 1720.6
5f	90.0		350.1016(350.1020)	3388.7, 1710.6
6a	87.3	91—93	276.0652(276.0653)	1608.9
6b	83.5	97—99	276.0656(276.0653)	1612.5
6c	79.2	89—91	276.0651(276.0653)	1610.7

Table 4 1H NMR and 13C NMR data for compounds 3—6

Compd.	¹H NMR(500 MHz), δ	¹³C NMR(125 MHz), δ
3a^a	6.93—7.81(m, 7H, PhH), 5.81(dd, 1H, OCH, J=9.5, 2.5 Hz), 3.69(s, 3H, OCH₃), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(d, 1H, CH₂, J=16.0 Hz)	169.67, 156.46, 150.92(dd, J_C—F=246.62, 12.62 Hz), 149.55(dd, J_C—F=251.62, 13.62 Hz), 144.01, 132.82, 129.97, 127.92, 125.70, 125.01, 124.65(dd, J_C—F=10.87, 4.37 Hz), 122.67, 119.45(d, J_C—F=17.00 Hz), 116.87, 69.83, 52.08, 34.87
3b^a	6.93—7.84(m, 7H, PhH), 5.84(dd, 1H, OCH, J=9.5, 2.5 Hz), 3.70(s, 3H, OCH₃), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(dd, 1H, CH₂, J=15.5, 2.5 Hz)	169.79, 158.98(dd, J_C—F=243.75, 3.37 Hz), 157.25(dd, J_C—F=247.00, 3.87 Hz), 156.13, 144.01, 132.80, 129.95, 127.90, 124.79(dd, J_C—F=13.37, 8.37 Hz), 122.67, 119.42(t, J_C—F=17.00 Hz), 117.31(dd, J_C—F=23.50, 11.25 Hz), 116.86, 116.39(t, J_C—F=22.50 Hz), 69.73, 52.07, 34.79
3c^a	6.95—8.00(m, 7H, PhH), 5.89(dd, 1H, OCH, J=9.5, 2.5 Hz), 3.76(s, 3H, OCH₃), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(dd, 1H, CH₂, J=16.0, 3.0 Hz)	169.82, 156.62, 150.92(dd, J_C—F=246.62, 12.62 Hz), 149.55(dd, J_C—F=251.62, 13.62 Hz), 143.42, 132.77, 129.60, 127.79, 123.08, 122.80, 116.95(dd, J_C—F=10.87, 4.37 Hz), 116.88, 67.75, 52.27, 35.26
3d^a	6.93—7.81(m, 7H, PhH), 5.81(dd, 1H, OCH, J=9.5, 2.5 Hz), 4.14(q, 2H, OCH₂, J=7.0 Hz), 2.86(dd, 1H, CH₂, J=16.0, 9.5 Hz), 2.61(d, 1H, CH₂, J=15.5 Hz), 1.24(t, 3H, CH₃, J=7.0 Hz)	169.21, 156.62, 150.92(dd, J_C—F=246.62, 12.62 Hz), 149.55(dd, J_C—F=251.62, 13.62 Hz), 144.10, 132.84, 129.94, 127.92, 125.78, 125.03, 124.65(dd, J_C—F=6.50, 4.37 Hz), 122.62, 119.43(d, J_C—F=17.00 Hz), 116.84, 69.91, 61.09, 35.20, 14.10
3e^a	6.93—7.83(m, 7H, PhH), 5.84(dd, 1H, OCH, J=9.5, 2.5 Hz), 4.14(q, 2H, OCH₂, J=7.0 Hz), 2.85(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.61(dd, 1H, CH₂, J=15.5, 2.5 Hz), 1.24(t, 3H, CH₃, J=7.0 Hz)	169.35, 158.98(dd, J_C—F=243.75, 3.37 Hz), 157.25(dd, J_C—F=247.00, 3.87 Hz), 156.23, 144.10, 132.82, 129.92, 127.90, 124.84(dd, J_C—F=13.37, 8.37 Hz), 122.63, 119.42(dd, J_C—F=17.00, 10.00 Hz), 117.31(dd, J_C—F=23.50, 11.25 Hz), 116.84, 116.39(dd, J_C—F=22.50, 5.00 Hz), 69.79, 61.09, 35.12, 14.13
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
3f^a	6.95—8.00(m, 7H, PhH), 5.89(dd, 1H, OCH, J=9.5, 2.5 Hz), 4.14(q, 2H, OCH₂, J=7.0 Hz), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(dd, 1H, CH₂, J=16.0, 3.0 Hz), 1.24(t, 3H, CH₃, J=7.0 Hz)	169.38, 156.73, 152.92(dd, J_C—F=246.62, 12.62 Hz), 150.45(dd, J_C—F=251.62, 13.62 Hz), 143.52, 132.81, 131.84, 129.55, 127.78, 123,12(dd, J_C—F=65.00, 3.50 Hz), 122.74, 116.95(dd, J_C—F=10.87, 4.37 Hz), 116.86, 67.84, 61.30, 35.56, 14.15
4a^a	6.99—7.12(m, 7H, PhH), 4.70(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.43(s, 1H, NH), 3.78(s, 3H, OCH₃), 3.42(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.89(t, 1H, CH₂, J=12.5 Hz)	173.03, 163.27, 150.84(dd, J_C—F=246.6, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 138.14, 137.70, 130.53(d, J_C—F=8.75 Hz), 128.98, 127.27, 125.06, 124.29(dd, J_C—F=6.50, 4.50 Hz), 121.82, 121.50, 118.40(d, J_C—F=17.12 Hz), 65.49, 52.67, 35.40
4b^a	6.99—7.69(m, 7H, PhH), 4.70(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.41(s, 1H, NH), 3.79(s, 3H, OCH₃), 3.43(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.85(t, 1H, CH₂, J=12.5 Hz)	173.07, 163.20, 158.84(dd, J_C—F=246.6, 13.25 Hz), 156.65(dd, J_C—F=250.00, 13.62 Hz), 138.16, 137.73, 129.58(dd, J_C—F=14.50, 7.25 Hz), 128.93, 127.27, 121.87, 121.53, 118.15(dd, J_C—F=24.62, 9.50 Hz), 117.77(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 65.59, 52.65, 35.14
4c^a	6.98—7.99(m, 7H, PhH), 4.55(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.34(s, 1H, NH), 3.82(s, 3H, OCH₃), 3.44(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.88(dd, 1H, CH₂, J=10.5, 3.0 Hz)	172.78, 163.20, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 138.79, 137.17, 135.86, 128.80, 126.94, 125.06, 123.34(dd, J_C—F=6.50, 4.50 Hz), 122.11, 121.38, 118.40(dd, J_C—F=123.25, 17.75 Hz), 65.81, 52.79, 31.70
4d^a	6.97—7.70(m, 7H, PhH), 4.66(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.43(s, 1H, NH), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.41(dd, 1H, CH₂, J=13.5, 3.5 Hz), 2.87(t, 1H, CH₂, J=12.5 Hz), 1.28(t, 3H, CH₃, J=7.5 Hz)	172.53, 163.39, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 138.14, 137.74, 130.53(d, J_C—F=8.75 Hz), 128.98, 127.26, 125.06, 124.29(dd, J_C—F=6.50, 4.50 Hz), 120.82, 121.47, 118.40(d, J_C—F=17.12 Hz), 65.58, 61.87, 35.41, 14.16
4e^a	6.97—7.68(m, 7H, PhH), 4.65(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.40(s, 1H, NH), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.42(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.84(t, 1H, CH₂, J=12.5 Hz)	172.58, 163.31, 157.84(dd, J_C—F=246.60, 13.25 Hz), 156.65(dd, J_C—F=250.00, 13.62 Hz), 138.14, 137.78, 129.68(dd, J_C—F=14.50, 7.25 Hz), 128.96, 127.24, 121.83, 121.50, 118.10(dd, J_C—F=24.62, 9.50 Hz), 117.75(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 65.66, 61.85, 35.17, 14.17
4f^a	6.97—7.78(m, 7H, PhH), 4.55(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.35(s, 1H, NH), 4.25(q, 2H, OCH₂, J=7.0 Hz), 3.42(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.88(dd, 1H, CH₂, J=10.5, 3.0 Hz)	172.28, 163.24, 150.64(dd, J_C—F=246.60, 13.25 Hz), 149.45(dd, J_C—F=250.00, 13.62 Hz), 138.80, 137.27, 135.97, 128.84, 126.92, 123.34(dd, J_C—F=6.50, 4.50 Hz), 122.05, 121.39, 118.40(dd, J_C—F=123.25, 17.75 Hz), 65.89, 62.01, 31.76, 14.24
5a^b	6.79—7.68(m, 7H, PhH), 5.42—5.45(m, 1H, NCH), 4.92(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 3.67(s, 3H, OCH₃), 2.53—2.59(m, 1H, CH₂), 2.35—2.40(m, 1H, CH₂)	173.03, 163.27, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 149.51, 128.98, 132.83, 128.72, 124.69(dd, J_C—F=6.50, 4.50 Hz), 124.07, 120.86, 120.08, 116.40(d, J_C—F=17.12 Hz), 51.73, 50.64, 43.17, 37.05
5b^b	6.79—7.68(m, 7H, PhH), 5.42—5.45(m, 1H, NCH), 4.92(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 3.67(s, 3H, OCH₃), 2.53—2.59(m, 1H, CH₂), 2.35—2.40(m, 1H, CH₂)	173.03, 163.27, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 149.51, 128.98, 132.83, 128.72, 124.69(dd, J_C—F=6.50, 4.50 Hz), 124.07, 120.86, 120.08, 116.40(d, J_C—F=17.12 Hz), 51.73, 50.64, 43.17, 37.05
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
5c^b	6.78—7.62(m, 7H, PhH), 5.06—5.09(m, 1H, NCH), 4.88(s, 1H, NH), 3.98(dd, 1H, NCH, J=10.0, 5.0 Hz), 3.66(s, 3H, OCH₃), 2.43—2.49(m, 1H, CH₂), 2.34—2.40(m, 1H, CH₂)	171.26, 150.55(dd, J_C—F=244.37, 12.50 Hz), 149.34(dd, J_C—F=250.00, 13.62 Hz), 149.18, 141.20, 133.04, 128.83, 123.73(dd, J_C—F=6.50, 4.50 Hz), 120.77, 120.03, 119.86, 117.03(dd, J_C—F=123.25, 17.75 Hz), 56.33, 51.73, 42.68, 38.14
5d^b	6.81—7.69(m, 7H, PhH), 5.43—5.46(m, 1H, NCH), 4.91(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 4.12(q, 2H, OCH₂, J=7.0 Hz), 2.55—2.60(m, 1H, CH₂), 2.37—2.42(m, 1H, CH₂), 1.23(t, 3H, CH₃, J=7.5 Hz)	170.57, 163.27, 150.64(dd, J_C—F=246.60, 13.25 Hz), 149.44(dd, J_C—F=250.00, 13.62 Hz), 149.32, 132.94, 132.70, 128.72, 124.67(dd, J_C—F=6.50, 4.50 Hz), 124.04, 120.91, 120.26, 120.15, 116.19(d, J_C—F=17.12 Hz), 60.91, 50.67, 43.38, 37.18, 13.56
5e^b	6.79—7.68(m, 7H, PhH), 5.42—5.45(m, 1H, NCH), 4.92(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 4.12(q, 2H, OCH₂, J=7.0 Hz), 2.53—2.59(m, 1H, CH₂), 2.35—2.40(m, 1H, CH₂), 1.23(t, 3H, CH₃, J=7.5 Hz)	173.03, 163.27, 150.64(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 149.51, 128.88, 132.53, 127.72, 124.59(dd, J_C—F=6.50, 4.50 Hz), 124.07, 120.86, 120.28, 116.43(d, J_C—F=17.12 Hz), 62.63, 52.64, 42.67, 37.65, 13.79
5f^b	6.78—7.62(m, 7H, PhH), 5.06—5.09(m, 1H, NCH), 4.88(s, 1H, NH), 3.98(dd, 1H, NCH, J=10.0, 5.0 Hz), 4.12(q, 2H, OCH₂, J=7.0 Hz), 2.43—2.49(m, 1H, CH₂), 2.34—2.40(m, 1H, CH₂), 1.23(t, 3H, CH₃, J=7.5 Hz)	171.26, 150.55(dd, J_C—F=244.37, 12.50 Hz), 149.34(dd, J_C—F=250.00, 13.62 Hz), 149.18, 141.20, 133.04, 128.83, 123.73(dd, J_C—F=6.50, 4.50 Hz), 120.77, 120.03, 119.86, 117.03(dd, J_C—F=123.25, 17.75 Hz), 66.30, 51.73, 42.68, 37.14, 13.46
6a^a	7.10—7.82(m, 7H, PhH), 3.69(t, 2H, SCH₂, J=7.0 Hz), 2.93(t, 2H, SCCH₂, J=7.0 Hz)	168.57, 151.86, 150.95(dd, J_C—F=247.12, 13.37 Hz), 149.70(dd, J_C—F=251.00, 13.87 Hz), 134.84, 129.65, 129.37(d, J_C—F=8.75 Hz), 125.53, 125.28, 125.10, 124.28(dd, J_C—F=6.50, 4.50 Hz), 123.88, 119.03(d, J_C—F=17.12 Hz), 41.25, 33.01
6b^a	7.10—7.92(m, 7H, PhH), 3.68(t, 2H, SCH₂, J=7.0 Hz), 2.94(t, 2H, SCCH₂, J=7.0 Hz)	168.59, 151.79, 150.90(dd, J_C—F=247.10, 13.35 Hz), 149.70(dd, J_C—F=251.00, 13.87 Hz), 134.83, 129.59, 129.36(d, J_C—F=8.75 Hz), 125.51, 125.29, 125.05, 124.22(dd, J_C—F=6.50, 4.50 Hz), 123.88, 119.00(d, J_C—F=17.12 Hz), 41.05, 32.01
6c^a	7.10—8.00(m, 7H, PhH), 3.66(t, 2H, SCH₂, J=7.0 Hz), 2.96(t, 2H, SCCH₂, J=7.0 Hz)	168.61, 152.33(dd, J_C—F=247.12, 13.37 Hz), 150.95(dd, J_C—F=247.12, 13.37 Hz), 149.70(dd, J_C—F=251.00, 13.87 Hz), 134.84, 129.65, 129.37(d, J_C—F=8.75 Hz), 125.53, 125.28, 125.10, 124.28(dd, J_C—F=6.50, 4.50 Hz), 123.88, 119.03(d, J_C—F=17.12 Hz), 41.53, 29.49

Table 4 1H NMR and 13C NMR data for compounds 3—6

Compd.	¹H NMR(500 MHz), δ	¹³C NMR(125 MHz), δ
3a^a	6.93—7.81(m, 7H, PhH), 5.81(dd, 1H, OCH, J=9.5, 2.5 Hz), 3.69(s, 3H, OCH₃), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(d, 1H, CH₂, J=16.0 Hz)	169.67, 156.46, 150.92(dd, J_C—F=246.62, 12.62 Hz), 149.55(dd, J_C—F=251.62, 13.62 Hz), 144.01, 132.82, 129.97, 127.92, 125.70, 125.01, 124.65(dd, J_C—F=10.87, 4.37 Hz), 122.67, 119.45(d, J_C—F=17.00 Hz), 116.87, 69.83, 52.08, 34.87
3b^a	6.93—7.84(m, 7H, PhH), 5.84(dd, 1H, OCH, J=9.5, 2.5 Hz), 3.70(s, 3H, OCH₃), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(dd, 1H, CH₂, J=15.5, 2.5 Hz)	169.79, 158.98(dd, J_C—F=243.75, 3.37 Hz), 157.25(dd, J_C—F=247.00, 3.87 Hz), 156.13, 144.01, 132.80, 129.95, 127.90, 124.79(dd, J_C—F=13.37, 8.37 Hz), 122.67, 119.42(t, J_C—F=17.00 Hz), 117.31(dd, J_C—F=23.50, 11.25 Hz), 116.86, 116.39(t, J_C—F=22.50 Hz), 69.73, 52.07, 34.79
3c^a	6.95—8.00(m, 7H, PhH), 5.89(dd, 1H, OCH, J=9.5, 2.5 Hz), 3.76(s, 3H, OCH₃), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(dd, 1H, CH₂, J=16.0, 3.0 Hz)	169.82, 156.62, 150.92(dd, J_C—F=246.62, 12.62 Hz), 149.55(dd, J_C—F=251.62, 13.62 Hz), 143.42, 132.77, 129.60, 127.79, 123.08, 122.80, 116.95(dd, J_C—F=10.87, 4.37 Hz), 116.88, 67.75, 52.27, 35.26
3d^a	6.93—7.81(m, 7H, PhH), 5.81(dd, 1H, OCH, J=9.5, 2.5 Hz), 4.14(q, 2H, OCH₂, J=7.0 Hz), 2.86(dd, 1H, CH₂, J=16.0, 9.5 Hz), 2.61(d, 1H, CH₂, J=15.5 Hz), 1.24(t, 3H, CH₃, J=7.0 Hz)	169.21, 156.62, 150.92(dd, J_C—F=246.62, 12.62 Hz), 149.55(dd, J_C—F=251.62, 13.62 Hz), 144.10, 132.84, 129.94, 127.92, 125.78, 125.03, 124.65(dd, J_C—F=6.50, 4.37 Hz), 122.62, 119.43(d, J_C—F=17.00 Hz), 116.84, 69.91, 61.09, 35.20, 14.10
3e^a	6.93—7.83(m, 7H, PhH), 5.84(dd, 1H, OCH, J=9.5, 2.5 Hz), 4.14(q, 2H, OCH₂, J=7.0 Hz), 2.85(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.61(dd, 1H, CH₂, J=15.5, 2.5 Hz), 1.24(t, 3H, CH₃, J=7.0 Hz)	169.35, 158.98(dd, J_C—F=243.75, 3.37 Hz), 157.25(dd, J_C—F=247.00, 3.87 Hz), 156.23, 144.10, 132.82, 129.92, 127.90, 124.84(dd, J_C—F=13.37, 8.37 Hz), 122.63, 119.42(dd, J_C—F=17.00, 10.00 Hz), 117.31(dd, J_C—F=23.50, 11.25 Hz), 116.84, 116.39(dd, J_C—F=22.50, 5.00 Hz), 69.79, 61.09, 35.12, 14.13
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
3f^a	6.95—8.00(m, 7H, PhH), 5.89(dd, 1H, OCH, J=9.5, 2.5 Hz), 4.14(q, 2H, OCH₂, J=7.0 Hz), 2.88(dd, 1H, CH₂, J=15.5, 9.5 Hz), 2.62(dd, 1H, CH₂, J=16.0, 3.0 Hz), 1.24(t, 3H, CH₃, J=7.0 Hz)	169.38, 156.73, 152.92(dd, J_C—F=246.62, 12.62 Hz), 150.45(dd, J_C—F=251.62, 13.62 Hz), 143.52, 132.81, 131.84, 129.55, 127.78, 123,12(dd, J_C—F=65.00, 3.50 Hz), 122.74, 116.95(dd, J_C—F=10.87, 4.37 Hz), 116.86, 67.84, 61.30, 35.56, 14.15
4a^a	6.99—7.12(m, 7H, PhH), 4.70(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.43(s, 1H, NH), 3.78(s, 3H, OCH₃), 3.42(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.89(t, 1H, CH₂, J=12.5 Hz)	173.03, 163.27, 150.84(dd, J_C—F=246.6, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 138.14, 137.70, 130.53(d, J_C—F=8.75 Hz), 128.98, 127.27, 125.06, 124.29(dd, J_C—F=6.50, 4.50 Hz), 121.82, 121.50, 118.40(d, J_C—F=17.12 Hz), 65.49, 52.67, 35.40
4b^a	6.99—7.69(m, 7H, PhH), 4.70(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.41(s, 1H, NH), 3.79(s, 3H, OCH₃), 3.43(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.85(t, 1H, CH₂, J=12.5 Hz)	173.07, 163.20, 158.84(dd, J_C—F=246.6, 13.25 Hz), 156.65(dd, J_C—F=250.00, 13.62 Hz), 138.16, 137.73, 129.58(dd, J_C—F=14.50, 7.25 Hz), 128.93, 127.27, 121.87, 121.53, 118.15(dd, J_C—F=24.62, 9.50 Hz), 117.77(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 65.59, 52.65, 35.14
4c^a	6.98—7.99(m, 7H, PhH), 4.55(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.34(s, 1H, NH), 3.82(s, 3H, OCH₃), 3.44(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.88(dd, 1H, CH₂, J=10.5, 3.0 Hz)	172.78, 163.20, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 138.79, 137.17, 135.86, 128.80, 126.94, 125.06, 123.34(dd, J_C—F=6.50, 4.50 Hz), 122.11, 121.38, 118.40(dd, J_C—F=123.25, 17.75 Hz), 65.81, 52.79, 31.70
4d^a	6.97—7.70(m, 7H, PhH), 4.66(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.43(s, 1H, NH), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.41(dd, 1H, CH₂, J=13.5, 3.5 Hz), 2.87(t, 1H, CH₂, J=12.5 Hz), 1.28(t, 3H, CH₃, J=7.5 Hz)	172.53, 163.39, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 138.14, 137.74, 130.53(d, J_C—F=8.75 Hz), 128.98, 127.26, 125.06, 124.29(dd, J_C—F=6.50, 4.50 Hz), 120.82, 121.47, 118.40(d, J_C—F=17.12 Hz), 65.58, 61.87, 35.41, 14.16
4e^a	6.97—7.68(m, 7H, PhH), 4.65(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.40(s, 1H, NH), 4.22(q, 2H, OCH₂, J=7.0 Hz), 3.42(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.84(t, 1H, CH₂, J=12.5 Hz)	172.58, 163.31, 157.84(dd, J_C—F=246.60, 13.25 Hz), 156.65(dd, J_C—F=250.00, 13.62 Hz), 138.14, 137.78, 129.68(dd, J_C—F=14.50, 7.25 Hz), 128.96, 127.24, 121.83, 121.50, 118.10(dd, J_C—F=24.62, 9.50 Hz), 117.75(dd, J_C—F=26.50, 8.37 Hz), 116.72(dd, J_C—F=25.37, 3.62 Hz), 65.66, 61.85, 35.17, 14.17
4f^a	6.97—7.78(m, 7H, PhH), 4.55(dd, 1H, NCH, J=11.0, 4.0 Hz), 4.35(s, 1H, NH), 4.25(q, 2H, OCH₂, J=7.0 Hz), 3.42(dd, 1H, CH₂, J=13.5, 4.0 Hz), 2.88(dd, 1H, CH₂, J=10.5, 3.0 Hz)	172.28, 163.24, 150.64(dd, J_C—F=246.60, 13.25 Hz), 149.45(dd, J_C—F=250.00, 13.62 Hz), 138.80, 137.27, 135.97, 128.84, 126.92, 123.34(dd, J_C—F=6.50, 4.50 Hz), 122.05, 121.39, 118.40(dd, J_C—F=123.25, 17.75 Hz), 65.89, 62.01, 31.76, 14.24
5a^b	6.79—7.68(m, 7H, PhH), 5.42—5.45(m, 1H, NCH), 4.92(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 3.67(s, 3H, OCH₃), 2.53—2.59(m, 1H, CH₂), 2.35—2.40(m, 1H, CH₂)	173.03, 163.27, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 149.51, 128.98, 132.83, 128.72, 124.69(dd, J_C—F=6.50, 4.50 Hz), 124.07, 120.86, 120.08, 116.40(d, J_C—F=17.12 Hz), 51.73, 50.64, 43.17, 37.05
5b^b	6.79—7.68(m, 7H, PhH), 5.42—5.45(m, 1H, NCH), 4.92(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 3.67(s, 3H, OCH₃), 2.53—2.59(m, 1H, CH₂), 2.35—2.40(m, 1H, CH₂)	173.03, 163.27, 150.84(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 149.51, 128.98, 132.83, 128.72, 124.69(dd, J_C—F=6.50, 4.50 Hz), 124.07, 120.86, 120.08, 116.40(d, J_C—F=17.12 Hz), 51.73, 50.64, 43.17, 37.05
Compd.	¹H NMR(500 MHz, CDCl₃), δ	¹³C NMR(125 MHz, CDCl₃), δ
5c^b	6.78—7.62(m, 7H, PhH), 5.06—5.09(m, 1H, NCH), 4.88(s, 1H, NH), 3.98(dd, 1H, NCH, J=10.0, 5.0 Hz), 3.66(s, 3H, OCH₃), 2.43—2.49(m, 1H, CH₂), 2.34—2.40(m, 1H, CH₂)	171.26, 150.55(dd, J_C—F=244.37, 12.50 Hz), 149.34(dd, J_C—F=250.00, 13.62 Hz), 149.18, 141.20, 133.04, 128.83, 123.73(dd, J_C—F=6.50, 4.50 Hz), 120.77, 120.03, 119.86, 117.03(dd, J_C—F=123.25, 17.75 Hz), 56.33, 51.73, 42.68, 38.14
5d^b	6.81—7.69(m, 7H, PhH), 5.43—5.46(m, 1H, NCH), 4.91(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 4.12(q, 2H, OCH₂, J=7.0 Hz), 2.55—2.60(m, 1H, CH₂), 2.37—2.42(m, 1H, CH₂), 1.23(t, 3H, CH₃, J=7.5 Hz)	170.57, 163.27, 150.64(dd, J_C—F=246.60, 13.25 Hz), 149.44(dd, J_C—F=250.00, 13.62 Hz), 149.32, 132.94, 132.70, 128.72, 124.67(dd, J_C—F=6.50, 4.50 Hz), 124.04, 120.91, 120.26, 120.15, 116.19(d, J_C—F=17.12 Hz), 60.91, 50.67, 43.38, 37.18, 13.56
5e^b	6.79—7.68(m, 7H, PhH), 5.42—5.45(m, 1H, NCH), 4.92(s, 1H, NH), 4.11(dd, 1H, NCH, J=10.0, 5.0 Hz), 4.12(q, 2H, OCH₂, J=7.0 Hz), 2.53—2.59(m, 1H, CH₂), 2.35—2.40(m, 1H, CH₂), 1.23(t, 3H, CH₃, J=7.5 Hz)	173.03, 163.27, 150.64(dd, J_C—F=246.60, 13.25 Hz), 149.65(dd, J_C—F=250.00, 13.62 Hz), 149.51, 128.88, 132.53, 127.72, 124.59(dd, J_C—F=6.50, 4.50 Hz), 124.07, 120.86, 120.28, 116.43(d, J_C—F=17.12 Hz), 62.63, 52.64, 42.67, 37.65, 13.79
5f^b	6.78—7.62(m, 7H, PhH), 5.06—5.09(m, 1H, NCH), 4.88(s, 1H, NH), 3.98(dd, 1H, NCH, J=10.0, 5.0 Hz), 4.12(q, 2H, OCH₂, J=7.0 Hz), 2.43—2.49(m, 1H, CH₂), 2.34—2.40(m, 1H, CH₂), 1.23(t, 3H, CH₃, J=7.5 Hz)	171.26, 150.55(dd, J_C—F=244.37, 12.50 Hz), 149.34(dd, J_C—F=250.00, 13.62 Hz), 149.18, 141.20, 133.04, 128.83, 123.73(dd, J_C—F=6.50, 4.50 Hz), 120.77, 120.03, 119.86, 117.03(dd, J_C—F=123.25, 17.75 Hz), 66.30, 51.73, 42.68, 37.14, 13.46
6a^a	7.10—7.82(m, 7H, PhH), 3.69(t, 2H, SCH₂, J=7.0 Hz), 2.93(t, 2H, SCCH₂, J=7.0 Hz)	168.57, 151.86, 150.95(dd, J_C—F=247.12, 13.37 Hz), 149.70(dd, J_C—F=251.00, 13.87 Hz), 134.84, 129.65, 129.37(d, J_C—F=8.75 Hz), 125.53, 125.28, 125.10, 124.28(dd, J_C—F=6.50, 4.50 Hz), 123.88, 119.03(d, J_C—F=17.12 Hz), 41.25, 33.01
6b^a	7.10—7.92(m, 7H, PhH), 3.68(t, 2H, SCH₂, J=7.0 Hz), 2.94(t, 2H, SCCH₂, J=7.0 Hz)	168.59, 151.79, 150.90(dd, J_C—F=247.10, 13.35 Hz), 149.70(dd, J_C—F=251.00, 13.87 Hz), 134.83, 129.59, 129.36(d, J_C—F=8.75 Hz), 125.51, 125.29, 125.05, 124.22(dd, J_C—F=6.50, 4.50 Hz), 123.88, 119.00(d, J_C—F=17.12 Hz), 41.05, 32.01
6c^a	7.10—8.00(m, 7H, PhH), 3.66(t, 2H, SCH₂, J=7.0 Hz), 2.96(t, 2H, SCCH₂, J=7.0 Hz)	168.61, 152.33(dd, J_C—F=247.12, 13.37 Hz), 150.95(dd, J_C—F=247.12, 13.37 Hz), 149.70(dd, J_C—F=251.00, 13.87 Hz), 134.84, 129.65, 129.37(d, J_C—F=8.75 Hz), 125.53, 125.28, 125.10, 124.28(dd, J_C—F=6.50, 4.50 Hz), 123.88, 119.03(d, J_C—F=17.12 Hz), 41.53, 29.49

Table 5 Zone(mm) of growth inhibition of compounds 2a

Compd.	C. albicans ATCC10231	C. Neofonmans			Compd.	C. albicans ATCC10231	C. Neofonmans
Compd.	C. albicans ATCC10231	ATCC 34874	Clinical isolate				ATCC 34874	Clinical isolate
2a	9.4	24.3		24.5	2o	6.0	17.3		21.2
2b	6.0	21.4		24.0	2p	6.0	6.0		6.0
2c	6.0	21.2		24.0	2q	6.0	6.0		6.0
2d	6.0	22.5		20.9	2r	6.0	6.0		6.0
2e	6.0	23.4		23.3	2s	6.0	6.0		6.0
2f	6.0	23.8		19.9	2t	6.0	15.3		15.3
2g	6.0	6.0		6.0	2u	6.0	13.8		13.7
2h	6.0	15.3		17.8	2v	6.0	10.3		10.2
2i	6.0	6.0		6.0	2w	6.0	6.0		6.0
2j	6.0	13.8		13.1	2x	6.0	6.0		6.0
2k	6.0	6.0		6.0	2y	6.0	6.0		6.0
2l	6.0	6.0		6.0	2z	6.0	6.0		6.0
2m	6.0	6.0		6.0	DMSO	6.0	6.0		6.0
2n	6.0	6.0		6.0	A^b	6.3	22.5		22.6

Table 6 MIC, MIC80 and MFC values(μg/mL) for compounds 2a—2f and fluconazole

Compd.	MIC		MIC₈₀		MFC
	C. Neofonmans		C. Neofonmans		C. Neofonmans
	ATCC 34874	Clinical isolate	ATCC 34874	Clinical isolate	ATCC 34874	Clinical isolate
2a	1.0	0.8	2.0	2.0	10.0	9.0
2b	1.5	1.5	2.0	2.0	12.0	10.0
2c	4.5	3.0	2.0	2.0	17.0	16.0
2d	2.0	2.0	1.5	1.5	12.0	12.0
2e	3.0	3.0	1.5	1.5	12.0	10.0
2f	5.0	4.0	2.0	2.0	15.0	16.0
Fluconazole	>128.0	>128.0	2.0	3.0	>128.0	>128.0

Table 7 Zone(mm) of growth inhibition of compounds 3—6a

Compd.	C. Neofonmans		Compd.	C. Neofonmans
Compd.	ATCC34874		Clinical isolate	ATCC34874	Clinical isolate
3a—3f	6.0	6.0	5a—5f	6.0	6.0
4a	13.4	13.5	6a—6c	6.0	6.0
4b	16.3	16.5	A^b	22.5	22.6
4c—4f	6.0	6.0

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