Synthesis and Biological Activity of Lipoic Acid Ester Derivatives†

doi:10.7503/cjcu20180270

Abstract

Abstract:

A series of lipoic acid derivatives was synthesized via the modification of carboxyl groups of lipoic acid, 23 target compounds were obtained and characterized by nuclear magnetic resonance and high resolution mass spectrometry. Lipoic acid derivatives were employed in order to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated and compared by the acrolein assay, 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium(ABTS) assay and ferric reducing antioxidant power(FRAP) assay. Acrolein scavenging activity test results showed that most compounds exhibited acrolein scavenging activities, compounds 3a, 3b, 3e, 3f, 3k, 3m, 3q, 3v and 3w had good acrolein scavenging activities, especially compound 3a showed the highest acrolein scavenging activity which was stronger than carnosine. The experimental results showed that most compounds exhibited DPPH scavenging activities, compounds 3o, 3p, 3v and 3w had good DPPH scavenging activities, especially compound 3w showed the highest DPPH scavenging activity, which was close to 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(Trolox) and Vitamin C. The results showed that most compounds exhibited ABTS scavenging activities, compounds 3b, 3e, 3u, 3v and 3w had good ABTS scavenging activities, especially compound 3w showed the highest ABTS scavenging activity, which was very close to trolox and Vitamin C. FRAP experimental results showed that most compounds exhibited reduction activities to ferric ion-2,4,6-tri(2-pyridyl)-s-triazine(Fe³⁺-TPTZ) complex, compounds 3b, 3v and 3w had good reduction activities to Fe³⁺-TPTZ complex, especially compound 3w showed the highest reduction activity to Fe³⁺-TPTZ complex, which was stronger than Vitamin C and trolox. The results showed that most compounds exhibited hydroxyl radical scavenging activities, compounds 3j and 3w had good hydroxyl radical scavenging activities, especially compound 3w showed the highest hydroxyl radical scavenging activity which was stronger than trolox. Plasma stability assay results showed that compared with lipoic acid, twenty-three compounds had good plasma stability.

Key words: Lipoic acid derivative, Acrolein scavenging, Antioxidant activity, Plasma stability

CLC Number:

O623

TrendMD:

ZHANG Luyun, XU Qian, XIA Guangqing, CONG Li, WANG Yu, ZHANG Hui, ZHU Junyi, ZANG Hao. Synthesis and Biological Activity of Lipoic Acid Ester Derivatives^†[J]. Chem. J. Chinese Universities, 2018, 39(10): 2198.

Figures/Tables 9

References 33

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Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3a	Light yellow oil	53	None	259.0329
3b	Light yellow oil	50	None	273.0487
3c	Light yellow oil	89	None	249.0877
3d	Light yellow oil	89	None	285.1959
3e	Light yellow oil	61	None	299.1490
3f	Light yellow oil	79	None	313.2271
3g	Light yellow oil	80	None	327.2429
3h	Light yellow oil	91	None	341.2583
3i	Light yellow oil	69	None	355.2741
3j	Light yellow oil	56	None	369.2899
3k	Light yellow oil	66	None	383.3055
3l	Light yellow oil	54	None	397.3211
3m	Light yellow oil	67	None	305.1645
3n	Light yellow oil	58	None	319.1805
3o	Light yellow oil	80	None	309.1594
3p	Light yellow oil	81	None	325.1368
3q	Light yellow oil	94	None	320.1755
Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3r	Light yellow oil	77	None	323.1389
3s	Light yellow solid	84	89—90	373.1545
3t	White solid	52	101—103	362.1860
3u	Light yellow oil	58	None	353.2586
3v	Light yellow oil	80	None	349.1431
3w	Light yellow oil	47	None	365.0705

Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3a	Light yellow oil	53	None	259.0329
3b	Light yellow oil	50	None	273.0487
3c	Light yellow oil	89	None	249.0877
3d	Light yellow oil	89	None	285.1959
3e	Light yellow oil	61	None	299.1490
3f	Light yellow oil	79	None	313.2271
3g	Light yellow oil	80	None	327.2429
3h	Light yellow oil	91	None	341.2583
3i	Light yellow oil	69	None	355.2741
3j	Light yellow oil	56	None	369.2899
3k	Light yellow oil	66	None	383.3055
3l	Light yellow oil	54	None	397.3211
3m	Light yellow oil	67	None	305.1645
3n	Light yellow oil	58	None	319.1805
3o	Light yellow oil	80	None	309.1594
3p	Light yellow oil	81	None	325.1368
3q	Light yellow oil	94	None	320.1755
Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3r	Light yellow oil	77	None	323.1389
3s	Light yellow solid	84	89—90	373.1545
3t	White solid	52	101—103	362.1860
3u	Light yellow oil	58	None	353.2586
3v	Light yellow oil	80	None	349.1431
3w	Light yellow oil	47	None	365.0705

Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3a	3.61(q, 2H), 3.57(s, 3H), 3.18(t, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.31(s, 2H), 1.87(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H)	172.8, 56.0, 51.1, 39.9, 38.1, 34.0, 33.1, 28.1, 24.2
3b	4.05(d, 2H), 3.61(q, 1H), 3.18(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.28(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H), 1.23(s, 1H), 1.17(s, 3H)	172.8, 59.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.2, 14.1
3c	3.96(s, 2H), 3.61(q, 1H), 3.18(q, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.30(s, 2H), 1.86(q, 1H), 1.67(d, 1H), 1.57(s, 5H), 1.38(d, 2H), 0.88(s, 3H)	172.8, 65.1, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 24.2, 21.5, 10.2
3d	4.01(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.54(s, 5H), 1.33(t, 4H), 0.88(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 30.2, 28.1, 24.2, 18.6, 13.5
3e	4.00(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.55(d, 5H), 1.37(s, 2H), 1.29(d, 4H), 0.87(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 27.8, 27.6, 24.2, 21.7, 13.8
3f	4.00(s, 2H), 3.60(q, 1H), 3.18(t, 1H), 3.11(t, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.55(s, 5H), 1.37(d, 2H), 1.27(s, 6H), 0.86(s, 3H)	172.8, 63.7, 56.0, 39.9, 38.1, 34.0, 33.3, 30.8, 28.1, 28.1, 25.0, 24.2, 22.0, 13.8
3g	4.00(s, 2H), 3.60(t, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(t, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(d, 8H), 0.86(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.1, 28.3, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3h	4.00(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.67(d, 1H), 1.55(s, 5H), 1.37(s, 2H), 1.26(d, 10H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.2, 28.6, 28.6, 28.1, 28.1, 25.4, 24.2, 22.0, 13.9
3i	4.00(s, 2H), 3.60(q, 1H), 3.17(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(d, 1H), 1.66(q, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(t, 12H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.8, 38.0, 34.0, 33.3, 31.2, 28.8, 28.6, 28.6, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3j	3.99(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(d, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 14H), 0.85(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.2, 28.9, 28.9, 28.6, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3k	3.99(s, 2H), 3.59(t, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 16H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3l	3.99(s, 2H), 3.59(q, 1H), 3.17(q, 1H), 3.12(s, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 18H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3m	7.42(t, 2H), 7.26(s, 1H), 7.12(t, 2H), 3.65(q, 1H), 3.20(d, 1H), 3.12(t, 1H), 2.59(s, 2H), 2.43(d, 1H), 1.90(t, 1H), 1.67(d, 4H), 1.48(d, 2H)	171.7, 150.5, 129.4, 129.4, 125.7, 121.8, 121.8, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.1
Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3n	7.36(d, 5H), 5.09(s, 2H), 3.59(q, 1H), 3.16(s, 1H), 3.10(t, 1H), 2.36(t, 3H), 1.84(q, 1H), 1.64(d, 1H), 1.56(q, 3H), 1.37(s, 2H)	172.6, 136.2, 128.4, 128.4, 127.9, 127.9, 127.9, 65.3, 56.0, 39.8, 38.1, 34.0, 33.3, 28.0, 24.2
3o	7.69(s, 1H), 6.50(d, 1H), 6.45(d, 1H), 5.04(s, 2H), 3.59(s, 1H), 3.17(d, 1H), 3.11(q, 1H), 2.39(d, 1H), 2.32(s, 2H), 1.85(q, 1H), 1.64(q, 1H), 1.54(s, 3H), 1.35(s, 2H)	172.4, 149.4, 143.6, 110.7, 110.7, 57.3, 56.0, 39.8, 38.1, 33.9, 33.1, 27.9, 24.1
3p	7.55(q, 1H), 7.16(d, 1H), 7.01(q, 1H), 5.25(s, 2H), 3.58(s, 1H), 3.16(s, 1H), 3.10(d, 1H), 2.39(s, 1H), 2.33(s, 2H), 1.84(t, 1H), 1.64(s, 1H), 1.55(s, 3H), 1.35(d, 2H)	172.5, 138.1, 128.3, 127.3, 126.8, 59.8, 56.0, 39.8, 38.1, 33.9, 33.2, 28.0, 24.2
3q	8.54(s, 1H), 7.81(s, 1H), 7.39(d, 1H), 7.33(s, 1H), 5.15(s, 2H), 3.61(s, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.42(s, 3H), 1.87(t, 1H), 1.58(s, 1H), 1.40(s, 3H), 1.23(s, 2H)	172.5, 155.7, 149.1, 136.9, 122.9, 121.5, 66.0, 56.0, 39.8, 38.1, 34.0, 33.2, 28.0, 24.1
3r	8.47(s, 1H), 8.22(d, 1H), 6.52(d, 1H), 3.62(d, 1H), 3.19(d, 1H), 3.12(t, 1H), 2.57(t, 2H), 2.42(q, 1H), 1.89(q, 1H), 1.70(s, 1H), 1.59—1.65(m, 3H), 1.47(q, 2H)	171.4, 170.1, 156.8, 149.7, 141.0, 116.8, 56.0, 39.8, 38.1, 34.0, 32.6, 27.8, 24.1
3s	8.07(d, 1H), 7.77(d, 1H), 7.27(s, 1H), 7.15(d, 1H), 6.48(d, 1H), 3.66(s, 1H), 3.19(s, 1H), 3.14(s, 1H), 2.63(s, 2H), 2.43(d, 1H), 1.90(d, 1H), 1.69(t, 3H), 1.61(s, 1H), 1.48(d, 2H)	171.3, 159.7, 154.1, 152.9, 143.8, 129.3, 118.6, 116.6, 115.5, 110.0, 56.0, 39.9, 38.1, 34.0, 33.3, 27.9, 23.9
3t	9.98(s, 1H), 7.58(d, 2H), 7.03(d, 2H), 3.65(q, 1H), 3.19(d, 1H), 3.12(d, 1H), 2.56(t, 2H), 2.43(d, 1H), 2.03(s, 3H), 1.89(d, 1H), 1.60—1.71(m, 4H), 1.46(d, 2H)	171.8, 168.2, 145.6, 136.9, 121.8, 121.8, 119.8, 119.8, 56.0, 39.9, 38.1, 34.0, 33.2, 28.0, 25.3, 24.1
3u	4.79(s, 1H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.24(s, 2H), 1.87(t, 2H), 1.63(q, 3H), 1.53(s, 3H), 1.36(s, 2H), 1.30(d, 1H), 1.06(s, 1H), 0.91(d, 6H), 0.87(d, 3H), 0.81(t, 2H)	172.2, 70.0, 56.0, 46.9, 43.6, 40.0, 39.9, 38.1, 34.0, 33.6, 32.7, 31.8, 28.0, 26.5, 25.2, 24.3, 22.1
3v	7.07(d, 2H), 6.77(d, 2H), 5.23(s, 1H), 4.24—4.27(m, 2H), 3.52(t, 1H), 3.17(t, 1H), 3.11(t, 1H), 2.86(s, 2H), 2.45(d, 1H), 2.29(d, 2H), 1.89(t, 1H), 1.63(q, 4H), 1.42(s, 1H), 1.38(s, 1H)	173.7, 154.4, 130.0, 130.0, 129.7, 115.4, 115.4, 65.1, 56.4, 40.2, 38.4, 34.5, 34.2, 34.1, 28.7, 24.6
3w	8.74(s, 1H), 8.68(s, 1H), 6.63(d, 1H), 6.60(d, 1H), 6.46(q, 1H), 4.12(s, 2H), 3.59(q, 1H), 3.17(s, 1H), 3.11(t, 1H), 2.68(s, 2H), 2.40(d, 1H), 2.27(s, 2H), 1.86(t, 1H), 1.63(d, 1H), 1.51(d, 3H), 1.34(t, 2H)	172.7, 145.0, 143.7, 128.5, 119.4, 116.1, 115.4, 64.6, 56.0, 40.1, 38.1, 34.0, 33.8, 33.4, 28.0, 24.2

Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3a	3.61(q, 2H), 3.57(s, 3H), 3.18(t, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.31(s, 2H), 1.87(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H)	172.8, 56.0, 51.1, 39.9, 38.1, 34.0, 33.1, 28.1, 24.2
3b	4.05(d, 2H), 3.61(q, 1H), 3.18(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.28(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H), 1.23(s, 1H), 1.17(s, 3H)	172.8, 59.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.2, 14.1
3c	3.96(s, 2H), 3.61(q, 1H), 3.18(q, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.30(s, 2H), 1.86(q, 1H), 1.67(d, 1H), 1.57(s, 5H), 1.38(d, 2H), 0.88(s, 3H)	172.8, 65.1, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 24.2, 21.5, 10.2
3d	4.01(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.54(s, 5H), 1.33(t, 4H), 0.88(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 30.2, 28.1, 24.2, 18.6, 13.5
3e	4.00(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.55(d, 5H), 1.37(s, 2H), 1.29(d, 4H), 0.87(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 27.8, 27.6, 24.2, 21.7, 13.8
3f	4.00(s, 2H), 3.60(q, 1H), 3.18(t, 1H), 3.11(t, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.55(s, 5H), 1.37(d, 2H), 1.27(s, 6H), 0.86(s, 3H)	172.8, 63.7, 56.0, 39.9, 38.1, 34.0, 33.3, 30.8, 28.1, 28.1, 25.0, 24.2, 22.0, 13.8
3g	4.00(s, 2H), 3.60(t, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(t, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(d, 8H), 0.86(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.1, 28.3, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3h	4.00(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.67(d, 1H), 1.55(s, 5H), 1.37(s, 2H), 1.26(d, 10H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.2, 28.6, 28.6, 28.1, 28.1, 25.4, 24.2, 22.0, 13.9
3i	4.00(s, 2H), 3.60(q, 1H), 3.17(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(d, 1H), 1.66(q, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(t, 12H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.8, 38.0, 34.0, 33.3, 31.2, 28.8, 28.6, 28.6, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3j	3.99(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(d, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 14H), 0.85(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.2, 28.9, 28.9, 28.6, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3k	3.99(s, 2H), 3.59(t, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 16H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3l	3.99(s, 2H), 3.59(q, 1H), 3.17(q, 1H), 3.12(s, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 18H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3m	7.42(t, 2H), 7.26(s, 1H), 7.12(t, 2H), 3.65(q, 1H), 3.20(d, 1H), 3.12(t, 1H), 2.59(s, 2H), 2.43(d, 1H), 1.90(t, 1H), 1.67(d, 4H), 1.48(d, 2H)	171.7, 150.5, 129.4, 129.4, 125.7, 121.8, 121.8, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.1
Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3n	7.36(d, 5H), 5.09(s, 2H), 3.59(q, 1H), 3.16(s, 1H), 3.10(t, 1H), 2.36(t, 3H), 1.84(q, 1H), 1.64(d, 1H), 1.56(q, 3H), 1.37(s, 2H)	172.6, 136.2, 128.4, 128.4, 127.9, 127.9, 127.9, 65.3, 56.0, 39.8, 38.1, 34.0, 33.3, 28.0, 24.2
3o	7.69(s, 1H), 6.50(d, 1H), 6.45(d, 1H), 5.04(s, 2H), 3.59(s, 1H), 3.17(d, 1H), 3.11(q, 1H), 2.39(d, 1H), 2.32(s, 2H), 1.85(q, 1H), 1.64(q, 1H), 1.54(s, 3H), 1.35(s, 2H)	172.4, 149.4, 143.6, 110.7, 110.7, 57.3, 56.0, 39.8, 38.1, 33.9, 33.1, 27.9, 24.1
3p	7.55(q, 1H), 7.16(d, 1H), 7.01(q, 1H), 5.25(s, 2H), 3.58(s, 1H), 3.16(s, 1H), 3.10(d, 1H), 2.39(s, 1H), 2.33(s, 2H), 1.84(t, 1H), 1.64(s, 1H), 1.55(s, 3H), 1.35(d, 2H)	172.5, 138.1, 128.3, 127.3, 126.8, 59.8, 56.0, 39.8, 38.1, 33.9, 33.2, 28.0, 24.2
3q	8.54(s, 1H), 7.81(s, 1H), 7.39(d, 1H), 7.33(s, 1H), 5.15(s, 2H), 3.61(s, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.42(s, 3H), 1.87(t, 1H), 1.58(s, 1H), 1.40(s, 3H), 1.23(s, 2H)	172.5, 155.7, 149.1, 136.9, 122.9, 121.5, 66.0, 56.0, 39.8, 38.1, 34.0, 33.2, 28.0, 24.1
3r	8.47(s, 1H), 8.22(d, 1H), 6.52(d, 1H), 3.62(d, 1H), 3.19(d, 1H), 3.12(t, 1H), 2.57(t, 2H), 2.42(q, 1H), 1.89(q, 1H), 1.70(s, 1H), 1.59—1.65(m, 3H), 1.47(q, 2H)	171.4, 170.1, 156.8, 149.7, 141.0, 116.8, 56.0, 39.8, 38.1, 34.0, 32.6, 27.8, 24.1
3s	8.07(d, 1H), 7.77(d, 1H), 7.27(s, 1H), 7.15(d, 1H), 6.48(d, 1H), 3.66(s, 1H), 3.19(s, 1H), 3.14(s, 1H), 2.63(s, 2H), 2.43(d, 1H), 1.90(d, 1H), 1.69(t, 3H), 1.61(s, 1H), 1.48(d, 2H)	171.3, 159.7, 154.1, 152.9, 143.8, 129.3, 118.6, 116.6, 115.5, 110.0, 56.0, 39.9, 38.1, 34.0, 33.3, 27.9, 23.9
3t	9.98(s, 1H), 7.58(d, 2H), 7.03(d, 2H), 3.65(q, 1H), 3.19(d, 1H), 3.12(d, 1H), 2.56(t, 2H), 2.43(d, 1H), 2.03(s, 3H), 1.89(d, 1H), 1.60—1.71(m, 4H), 1.46(d, 2H)	171.8, 168.2, 145.6, 136.9, 121.8, 121.8, 119.8, 119.8, 56.0, 39.9, 38.1, 34.0, 33.2, 28.0, 25.3, 24.1
3u	4.79(s, 1H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.24(s, 2H), 1.87(t, 2H), 1.63(q, 3H), 1.53(s, 3H), 1.36(s, 2H), 1.30(d, 1H), 1.06(s, 1H), 0.91(d, 6H), 0.87(d, 3H), 0.81(t, 2H)	172.2, 70.0, 56.0, 46.9, 43.6, 40.0, 39.9, 38.1, 34.0, 33.6, 32.7, 31.8, 28.0, 26.5, 25.2, 24.3, 22.1
3v	7.07(d, 2H), 6.77(d, 2H), 5.23(s, 1H), 4.24—4.27(m, 2H), 3.52(t, 1H), 3.17(t, 1H), 3.11(t, 1H), 2.86(s, 2H), 2.45(d, 1H), 2.29(d, 2H), 1.89(t, 1H), 1.63(q, 4H), 1.42(s, 1H), 1.38(s, 1H)	173.7, 154.4, 130.0, 130.0, 129.7, 115.4, 115.4, 65.1, 56.4, 40.2, 38.4, 34.5, 34.2, 34.1, 28.7, 24.6
3w	8.74(s, 1H), 8.68(s, 1H), 6.63(d, 1H), 6.60(d, 1H), 6.46(q, 1H), 4.12(s, 2H), 3.59(q, 1H), 3.17(s, 1H), 3.11(t, 1H), 2.68(s, 2H), 2.40(d, 1H), 2.27(s, 2H), 1.86(t, 1H), 1.63(d, 1H), 1.51(d, 3H), 1.34(t, 2H)	172.7, 145.0, 143.7, 128.5, 119.4, 116.1, 115.4, 64.6, 56.0, 40.1, 38.1, 34.0, 33.8, 33.4, 28.0, 24.2

Compd.	Scavenging ratio(%)			Compd.	Scavenging ratio(%)
Compd.	1 h	2 h	3 h	Compd.	1 h	2 h	3 h
3a	66.8±0.9	86.6±1.0	96.6±0.9	3n	48.0±0.5	58.9±0.8	63.9±1.1
3b	67.0±0.6	77.8±0.9	88.2±1.2	3o	53.1±0.4	61.9±0.9	71.8±0.8
3c	37.1±1.4	48.9±1.4	58.9±1.5	3p	53.9±0.6	63.7±0.7	68.2±0.9
3d	42.5±1.7	55.2±1.6	72.5±1.4	3q	45.3±0.6	57.5±0.8	82.5±1.4
3e	76.0±1.9	84.1±1.7	90.0±1.9	3r	52.5±0.4	65.9±0.7	77.5±0.7
3f	55.3±0.9	76.3±1.7	87.3±1.8	3s	50.0±0.5	62.5±0.6	72.5±0.8
3g	45.9±1.4	58.9±1.3	68.4±1.7	3t	48.9±0.4	68.7±0.7	76.9±1.1
3h	37.7±0.6	53.8±1.6	58.7±1.4	3u	57.5±0.5	72.5±0.8	77.5±1.4
3i	47.0±0.7	52.5±0.6	57.5±1.1	3v	74.8±0.3	84.9±0.8	93.1±1.0
3j	42.9±0.4	66.6±1.4	74.1±1.5	3w	58.1±0.4	74.9±0.7	82.4±0.8
3k	61.9±0.7	70.6±0.9	82.5±1.4	Lipoic acid	25.7±0.2	47.5±0.7	57.5±0.8
3l	42.5±0.9	57.5±1.1	72.5±1.3	Carnosine	79.2±1.4	89.6±1.0	96.2±1.1
3m	37.5±0.5	57.5±1.4	82.5±1.2	GSH	90.0±0.7	100.0±0.5	100.0±0.3