Synthesis and Anti-HBV Activities of the Indirect Galactopyranosyl Derivatives of Matijin-Su†

doi:10.7503/cjcu20160222

Abstract

Abstract:

To explore the effect of the length of the linker on the activities of the derivatives of Matijin-Su(MTS) with potential for hepatic targeting, six galactosyl derivatives of MTS with potential for hepatic targeting were synthesized by binding galactosyl to derivatives of MTS using triethylene glycol or tetraethylene glycol as a linking arm, and their structures were confirmed by means of ¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMQC and ESI-MS. The anti-HBV activities of those compounds were evaluated using HepG2 2.2.15 cells. The screening results showed that all the target compounds had inhibitory effect on HBV DNA replication in HepG2 2.2.15 cells in a dose-response manner. The inhibition rates of compounds 15b(72.24%), 15c(56.49%), 15f(65.24%) on the replication of HBV DNA were better than other tested compounds, when the in concentration of the drug was 50 μg/mL. The results can provide reference for further research of hepatic targeting MTS derivatives. For the evaluation of the hepatic target distribution of galactopyranosyl derivatives of MTS, compound 15b with best anti HBV activity will be selected to do tissue distribution experiments in vivo and comparative study with derivative of MTS(13b) and Y101.

Key words: Hepatic targeting, Glacatose, Derivatives of Matijin-Su(MTS), Anti-hepatitis B virus activity

CLC Number:

O629

TrendMD:

XU Guangcan,YUAN Jie,LIU Qingchuan,HUANG Zhengming,LIANG Guangyi,XU Bixue. Synthesis and Anti-HBV Activities of the Indirect Galactopyranosyl Derivatives of Matijin-Su^†[J]. Chem. J. Chinese Universities, 2016, 37(8): 1451.

Figures/Tables 10

Fig.1 Chemical structures of MTS(A) and Y101(B)

Fig.2 General structure of hepatic targeting MTS derivatives

Scheme 1 Synthetic routes of target compounds 15a—15f (1) Ac2O, CH3COONa, 140 ℃; (2) 4-methylphenylsulfonyl chloride, pyridine, r.t.; (3) 0.4 nm molecular sieves, BF3·Et2O, CH2Cl2, 0 ℃ to r.t.; (4) phthalimide potassium, DMF, 110 ℃; (5) N2H4·H2O, MeOH, H2O, 80 ℃; (6)(Boc)2O, NaHCO3, EtOH, r.t.; (7) Ac2O, pyridine, r.t.; (8) TFA, CH2Cl2, 0 ℃; (9) IBCF, NMM, CH2Cl2/DMF, 0 ℃ to r.t.; (10) (a) NaOH, DMF, r.t.; (b) IBCF, NMM, CH2Cl2/DMF, 0 ℃ to r.t.; (11) NaOH, DMF, r.t.; (12) IBCF, NMM, CH2Cl2/DMF, 0 ℃ to r.t.; (13) CH3ONa, CH3OH/CH2Cl2, r.t..

Table 1 Appearance, yields, melting points, specific rotation and ESI-MS data for all the intermediates*

Compd.	Appearance	Yield(%)	m.p./℃	[α $] D 20$ /(°)(c=0.5, CH₃OH)	ESI-MS, m/z
3a	Pale oil	40
3b	Pale oil	55
4a	Pale oil	49			657.0[M+Na]⁺
4b	Pale oil	45
5a	Pale oil	87
5b	Pale oil	84
8a	Pale oil	79			580.1[M+H]⁺
8b	Pale oil	82			626.5[M+Na]⁺
9a	Pale oil				502.0[M+Na]⁺
9b	Pale oil				524.1[M+H]⁺
14a	White solid	79	130—132	-29.89	896.4[M+H]⁺
14b	White solid	83	133—134	-31.37	1026.3[M+Na]⁺
14c	White solid	65	145—146	-43.17	978.4[M+Na]⁺
14d	White solid	97	128—129	-27.82	962.2[M+Na]⁺
14e	White solid	79	132—135	-33.39	1048.3[M+H]⁺
14f	White solid	68	146—148	-34.68	1022.3[M+Na]⁺

Table 1 Appearance, yields, melting points, specific rotation and ESI-MS data for all the intermediates*

Compd.	Appearance	Yield(%)	m.p./℃	[α $] D 20$ /(°)(c=0.5, CH₃OH)	ESI-MS, m/z
3a	Pale oil	40
3b	Pale oil	55
4a	Pale oil	49			657.0[M+Na]⁺
4b	Pale oil	45
5a	Pale oil	87
5b	Pale oil	84
8a	Pale oil	79			580.1[M+H]⁺
8b	Pale oil	82			626.5[M+Na]⁺
9a	Pale oil				502.0[M+Na]⁺
9b	Pale oil				524.1[M+H]⁺
14a	White solid	79	130—132	-29.89	896.4[M+H]⁺
14b	White solid	83	133—134	-31.37	1026.3[M+Na]⁺
14c	White solid	65	145—146	-43.17	978.4[M+Na]⁺
14d	White solid	97	128—129	-27.82	962.2[M+Na]⁺
14e	White solid	79	132—135	-33.39	1048.3[M+H]⁺
14f	White solid	68	146—148	-34.68	1022.3[M+Na]⁺

Table 2 1H NMR data for intermediates 3 and 4*

Compd.	¹H NMR(CDCl₃), δ
3a	7.80(d, J=8.3 Hz, 2H), 7.35(d, J=8.0 Hz, 2H), 4.17(t, J=4.8 Hz, 2H), 3.75—3.68(m, 4H), 3.63—3.55(m, 6H), 2.45(s, 3H)
3b	7.79(d, J=8.3 Hz, 2H), 7.33(d, J=8.0 Hz, 2H), 4.15(t, J=4.8 Hz, 2H), 3.75—3.56(m, 14H), 2.44(s, 3H)
4a	7.79(d, J=8.3 Hz, 2H), 7.34(d, J=7.9 Hz, 2H), 5.38(dd, J=3.4, 1.0 Hz, 1H), 5.20(dd, J=10.5, 8.0 Hz, 1H), 5.02(dd, J=10.5, 3.4 Hz, 1H), 4.56(d, J=8.0 Hz, 1H), 4.20—4.09(m, 4H), 3.98—3.89(m, 2H), 3.73(ddd, J=11.0, 7.0, 3.9 Hz, 1H), 3.70—3.55(m, 8H), 2.45(s, 3H), 2.15(s, 3H), 2.05(s, 3H), 2.05(s, 3H), 1.99(s, 3H)
4b	7.79(d, J=8.3 Hz, 2H), 7.35(d, J=8.1 Hz, 2H), 5.38(dd, J=2.6, 0.8 Hz, 1H), 5.19(dd, J=10.5, 8.0 Hz, 1H), 5.01(dd, J=10.5, 3.4 Hz, 1H), 4.56(d, J=8.0 Hz, 1H), 4.19—4.08(m, 4H), 4.00—3.84(m, 2H), 3.80—3.55(m, 13H), 2.44(s, 3H), 2.14(s, 3H), 2.04(d, J=3.1 Hz, 6H), 1.97(s, 3H)

Table 3 1H NMR and 13C NMR data for intermediates 5, 8 and 14

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
5a	7.84(dd, J=5.5, 3.0 Hz, 2H), 7.71(dd, J=5.5, 3.0 Hz, 2H), 5.38(dd, J=3.4, 0.9 Hz, 1H), 5.19(dd, J=10.5, 8.0 Hz, 1H), 5.02(dd, J=10.5, 3.4 Hz, 1H), 4.55(d, J=8.0 Hz, 1H), 4.20—4.08(m, 2H), 3.95—3.52(m, 13H), 2.14(s, 3H), 2.04(s, 6H), 1.97(s, 3H)	170.6, 170.4, 170.3, 169.7, 168.4, 168.4, 134.1, 132.2, 123.4, 101.5, 71.0, 70.8, 70.7, 70.5, 70.2, 69.2, 69.0, 68.1, 67.2, 61.5, 37.3, 20.9, 20.8, 20.8, 20.8
5b	7.85(dd, J=5.5, 3.0 Hz, 2H), 7.74(dd, J=5.5, 3.0 Hz, 2H), 5.40(dd, J=3.4, 0.8 Hz, 1H), 5.21(dd, J=10.5, 8.0 Hz, 1H), 5.03(dd, J=10.5, 3.4 Hz, 1H), 4.59(d, J=8.0 Hz, 1H), 4.22—4.13(m, 2H), 4.03—3.52(m, 17H), 2.15(s, 3H), 2.06(s, 3H), 2.05(s, 3H), 1.99(s, 3H)	170.6, 170.4, 170.3, 169.7,168.43, 168.39, 134.1, 132.2, 123.4, 101.5, 71.0, 70.79, 70.76 70.7, 70.5, 70.3, 70.2, 69.2, 69.0, 68.1, 67.2, 61.5, 37.3, 20.9, 20.84, 20.82, 20.8
8a	5.26(t, J=8.6 Hz, 1H), 5.10(s, 1H), 4.94(dd, J=10.2, 3.2 Hz, 1H), 4.54(d, J=7.8 Hz, 1H), 4.32(dd, J=6.3, 4.5 Hz, 2H), 4.05(d, J=2.8 Hz, 1H), 3.81—3.51(m, 12H), 2.11(s, 3H), 2.09(s, 3H), 2.06(s, 3H), 1.84(s, 3H),1.45(s, 9H)	170.6, 170.4, 170.3, 169.6, 156.1, 101.58, 71.0, 70.8, 70.8,70.72, 70.65, 69.2, 69.0, 67.2, 61.4, 40.5, 28.6, 28.0, 21.0, 19.8, 19.7
8b	5.37(dd, J=8.4, 1.0 Hz, 1H), 5.20(dd, J=10.5, 8.0 Hz, 1H), 5.01(dd, J=10.5, 3.4 Hz, 1H), 4.56(d, J=8.0 Hz, 1H), 4.21—4.07(m, 2H), 4.00—3.87(m, 2H), 3.81—3.70(m, 1H), 3.70—3.30(m, 14H), 2.14(s, 3H), 2.05(s, 3H), 2.04(s, 3H), 1.97(s, 3H), 1.43(s, 9H)	170.5, 170.4, 170.3, 169.6, 156.1, 101.5, 71.0, 70.83, 70.77, 70.72, 70.65, 70.41, 70.37, 69.2, 69.0, 67.2, 61.4, 40.5, 28.6, 28.0, 20.9, 20.8, 20.7
14a	7.68(dd, J=8.8, 5.3 Hz, 2H), 7.31—7.04(m, 12H), 6.75—6.65(m, 2H), 6.39(t, J=4.4 Hz, 1H), 5.39(d, J=2.6 Hz, 1H), 5.22(dd, J=10.5, 7.9 Hz, 1H), 5.04(dd, J=10.5, 3.4 Hz, 1H), 4.87—4.77(m, 1H), 4.64—4.53(m, 2H), 4.22—4.07(m, 2H), 4.00—3.89(m, 2H), 3.77—3.68(m, 1H), 3.67—3.42(m, 7H), 3.42—3.31(m, 3H), 3.13(d, J=7.1 Hz, 2H), 3.01(d, J=6.9 Hz, 2H), 2.12(s, 3H), 2.04(s, 3H), 2.02(s, 3H), 1.98(s, 3H)	170.6,170.41, 170.36, 170.3, 169.8, 166.3, 166.2, 163.8, 136.6, 136.4, 129.93, 129.90, 129.7, 129.6, 129.44, 129.42, 128.9, 128.6, 127.3, 127.0, 115.9, 115.7, 101. 4, 71.0, 70.8, 70.7, 70.3, 70.3, 69.7, 69.2, 69.0, 67.2, 61.4, 54.8, 54.6, 39.4, 38.1, 38.2, 20.9, 20.8, 20.80, 20.75
14b	7.98(s, 1H), 7.81(d, J=8.1 Hz, 1H), 7.61(d, J=7.9 Hz, 1H), 7.30—7.04(m, 11H), 6.94—6.86(m, 2H), 6.47(t, J=4.9 Hz, 1H), 5.38(d, J=3.3 Hz, 1H), 5.21(dd, J=10.5, 8.0 Hz, 1H), 5.04(dd, J=10.5, 3.4 Hz, 1H), 4.92—4.83(m, 1H), 4.69—4.59(m, 1H), 4.55(d, J=8.0 Hz, 1H), 4.21—4.07(m, 2H), 4.00—3.88(m, 2H), 3.77—3.67(m, 1H), 3.66—3.41(m, 7H), 3.40—3.29(m, 3H), 3.11(d, J=6.9 Hz, 2H), 3.00(d, J=7.0 Hz, 2H), 2.12(s, 3H), 2.03(s, 3H), 2.02(s, 3H), 1.98(s, 3H)	170.5, 170.4, 170.3,170.21, 170.16, 169.7, 165.6, 140.6, 136.4, 136.3, 136.2, 135.6, 130.1, 129.3, 128.6, 128.4, 127.0, 126.8, 126.2, 101.2, 94.1, 70.8, 70.6, 70.5, 70.1, 70.1, 69.5, 69.0, 68.8, 67.0, 61.2, 54.7, 54.5, 39.2, 38.6, 38.1, 20.8, 20.64, 20.61, 20.57
14c	7.61(d, J=8.6 Hz, 2H), 7.39(d, J=8.5 Hz, 2H), 7.20—7.07(m, 7H), 6.80(d, J=8.6 Hz, 2H), 6.71(d, J=7.3 Hz, 1H), 6.62(d, J=7.8 Hz, 1H), 6.37(t, J=4.9 Hz, 1H), 5.39(d, J=2.6 Hz, 1H), 5.22(dd, J=10.5, 8.0 Hz, 1H), 5.05(dd, J=10.5, 3.4 Hz, 1H), 4.80—4.68(m, 1H), 4.63—4.53(m, 2H), 4.23—4.08(m, 2H), 4.02—3.90(m, 4H), 3.77—3.67(m, 1H), 3.65—3.33(m, 10H), 3.10—3.05(m, 2H, 3a-H), 3.02(d, J=6.8 Hz, 2H), 2.13(s, 3H), 2.04(s, 3H), 2.03(s, 3H,), 1.99(s, 3H), 1.39(t, J=7.0 Hz, 3H)	170.61, 170.59, 170.41, 170.35,170.3, 169.8, 166.2, 158.2, 138.3, 136.6, 132.2, 130.5 129.4, 129.0, 128.7, 128.6, 128.0, 127.0, 114.9, 101.5, 71.0, 70.81, 70.75, 70.4, 70.3, 69.7, 69.3, 69.0, 67.2, 63.5, 61.4, 55.0, 54.6, 39.4, 38.5, 37.3, 21.0, 20.83, 20.80, 20.75, 15.0
14d	7.69(dd, J=8.8, 5.3 Hz, 2H), 7.31—7.05(m, 12H), 6.77(d, J=7.6 Hz, 2H), 6.43(t, J=4.3 Hz, 1H), 5.38(d, J=3.4 Hz, 1H,), 5.21(dd, J=10.5, 7.9 Hz, 1H), 5.05(dd, J=10.5, 3.4 Hz, 1H) 4.87—4.77(m, 1H), 4.63—4.55(m, 2H), 4.20—4.08(m, 2H), 3.98—3.90(m, 2H), 3.79—3.69(m, 1H), 3.66—3.43(m, 11H), 3.42—3.30(m, 3H), 3.13(d, J=6.9 Hz, 2H), 3.01(d, J=6.9 Hz, 2H), 2.13(s, 3H), 2.03(s, 3H), 2.02(s, 3H), 1.97(s, 3H)	170.63, 170.57, 170.41, 170.38,170.3, 169.7, 166.3, 166.2, 163.8, 136.6, 136.5, 129.98, 129.95, 129.7, 129.6, 129.4, 129.0, 128.6, 127.2, 126.9, 115.8, 115.6, 101.3, 71.0, 70.8, 70.7, 70.61, 70.58, 70.32, 70.29, 69.7, 69.1, 68.9, 67.2, 61.4, 54.8, 54.6, 39.4, 38.7, 38.2, 20.9, 20.80, 20.78, 20.75
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
14e	7.98(s, 1H), 7.81(d, J=8.1 Hz, 1H), 7.61(d, J=7.9 Hz, 1H), 7.30—7.04(m, 11H), 6.92(d, J=7.8 Hz, 2H), 6.49(t, J=5.0 Hz, 1H), 5.38(d, J=3.3 Hz, 1H), 5.20(dd, J=10.5, 8.0 Hz, 1H), 5.05(dd, J=10.5, 3.4 Hz, 1H), 4.91—4.82(m, 1H), 4.67—4.56(m, 2H), 4.20—4.07(m, 2H), 3.98—3.90(m, 2H), 3.77—3.69(m, 1H), 3.67—3.48(m, 10H), 3.48—3.29(m, 4H), 3.11(d, J=6.9 Hz, 2H), 3.01(dd, J=6.9, 1.5 Hz, 2H), 2.12(s, 3H), 2.03(s, 3H), 2.01(s, 3H), 1.97(s, 3H)	170.5, 170.4, 170.23, 170.21, 170.19, 169.5, 165.6, 140.5, 136.4, 136.3, 136.2, 135.7, 130.1, 129.3, 129.2, 128.7, 128.3, 127.0, 126.7, 126.3, 101.1, 94.1, 70.8, 70.5, 70.5, 70.41, 70.38, 70.12, 70.09, 69.4, 68.9, 68.8, 67.0, 61.2, 54.7, 54.4, 39.2, 38.6, 38.1, 20.7, 20.62, 20.60, 20.58
14f	7.63(d, J=8.7 Hz, 2H), 7.39(d, J=8.7 Hz, 2H), 7.19—7.06(m, 7H), 6.79(d, J=8.6 Hz, 2H), 5.39(dd, J=3.4, 1.0 Hz, 1H), 5.22(dd, J=10.5, 7.9 Hz, 1H), 5.06(dd, J=10.5, 3.4 Hz, 1H), 4.83—4.76(m, 1H), 4.65—4.57(m, 2H), 4.20—4.09(m, 2H), 4.01—3.92(m, 4H), 3.78—3.70(m, 1H), 3.67—3.29(m, 14H), 3.07(dd, J=6.7, 2.3 Hz, 2H), 3.02(d, J=6.9 Hz, 2H), 2.13(s, 3H), 2.05(s, 3H), 2.03(s, 3H), 1.98(s, 3H), 1.38(t, J=7.0 Hz, 3H)	170.7, 170.6, 170.39, 170.36, 170.3, 169.7, 166.2, 158.2, 138.2, 136.6, 132.2, 130.4, 129.4, 128.9, 128.7, 128.68, 128.1, 127.0, 114.8, 101.4, 71.0, 70.8, 70.7, 70.6, 70.6, 70.3, 70.3, 69.6, 69.1, 68.9, 67.2, 63.5, 61.4, 55.0, 54.6, 39.3, 38.6, 37.4, 20.9, 20.80, 20.78, 20.7, 15.0

Table 3 1H NMR and 13C NMR data for intermediates 5, 8 and 14

Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
5a	7.84(dd, J=5.5, 3.0 Hz, 2H), 7.71(dd, J=5.5, 3.0 Hz, 2H), 5.38(dd, J=3.4, 0.9 Hz, 1H), 5.19(dd, J=10.5, 8.0 Hz, 1H), 5.02(dd, J=10.5, 3.4 Hz, 1H), 4.55(d, J=8.0 Hz, 1H), 4.20—4.08(m, 2H), 3.95—3.52(m, 13H), 2.14(s, 3H), 2.04(s, 6H), 1.97(s, 3H)	170.6, 170.4, 170.3, 169.7, 168.4, 168.4, 134.1, 132.2, 123.4, 101.5, 71.0, 70.8, 70.7, 70.5, 70.2, 69.2, 69.0, 68.1, 67.2, 61.5, 37.3, 20.9, 20.8, 20.8, 20.8
5b	7.85(dd, J=5.5, 3.0 Hz, 2H), 7.74(dd, J=5.5, 3.0 Hz, 2H), 5.40(dd, J=3.4, 0.8 Hz, 1H), 5.21(dd, J=10.5, 8.0 Hz, 1H), 5.03(dd, J=10.5, 3.4 Hz, 1H), 4.59(d, J=8.0 Hz, 1H), 4.22—4.13(m, 2H), 4.03—3.52(m, 17H), 2.15(s, 3H), 2.06(s, 3H), 2.05(s, 3H), 1.99(s, 3H)	170.6, 170.4, 170.3, 169.7,168.43, 168.39, 134.1, 132.2, 123.4, 101.5, 71.0, 70.79, 70.76 70.7, 70.5, 70.3, 70.2, 69.2, 69.0, 68.1, 67.2, 61.5, 37.3, 20.9, 20.84, 20.82, 20.8
8a	5.26(t, J=8.6 Hz, 1H), 5.10(s, 1H), 4.94(dd, J=10.2, 3.2 Hz, 1H), 4.54(d, J=7.8 Hz, 1H), 4.32(dd, J=6.3, 4.5 Hz, 2H), 4.05(d, J=2.8 Hz, 1H), 3.81—3.51(m, 12H), 2.11(s, 3H), 2.09(s, 3H), 2.06(s, 3H), 1.84(s, 3H),1.45(s, 9H)	170.6, 170.4, 170.3, 169.6, 156.1, 101.58, 71.0, 70.8, 70.8,70.72, 70.65, 69.2, 69.0, 67.2, 61.4, 40.5, 28.6, 28.0, 21.0, 19.8, 19.7
8b	5.37(dd, J=8.4, 1.0 Hz, 1H), 5.20(dd, J=10.5, 8.0 Hz, 1H), 5.01(dd, J=10.5, 3.4 Hz, 1H), 4.56(d, J=8.0 Hz, 1H), 4.21—4.07(m, 2H), 4.00—3.87(m, 2H), 3.81—3.70(m, 1H), 3.70—3.30(m, 14H), 2.14(s, 3H), 2.05(s, 3H), 2.04(s, 3H), 1.97(s, 3H), 1.43(s, 9H)	170.5, 170.4, 170.3, 169.6, 156.1, 101.5, 71.0, 70.83, 70.77, 70.72, 70.65, 70.41, 70.37, 69.2, 69.0, 67.2, 61.4, 40.5, 28.6, 28.0, 20.9, 20.8, 20.7
14a	7.68(dd, J=8.8, 5.3 Hz, 2H), 7.31—7.04(m, 12H), 6.75—6.65(m, 2H), 6.39(t, J=4.4 Hz, 1H), 5.39(d, J=2.6 Hz, 1H), 5.22(dd, J=10.5, 7.9 Hz, 1H), 5.04(dd, J=10.5, 3.4 Hz, 1H), 4.87—4.77(m, 1H), 4.64—4.53(m, 2H), 4.22—4.07(m, 2H), 4.00—3.89(m, 2H), 3.77—3.68(m, 1H), 3.67—3.42(m, 7H), 3.42—3.31(m, 3H), 3.13(d, J=7.1 Hz, 2H), 3.01(d, J=6.9 Hz, 2H), 2.12(s, 3H), 2.04(s, 3H), 2.02(s, 3H), 1.98(s, 3H)	170.6,170.41, 170.36, 170.3, 169.8, 166.3, 166.2, 163.8, 136.6, 136.4, 129.93, 129.90, 129.7, 129.6, 129.44, 129.42, 128.9, 128.6, 127.3, 127.0, 115.9, 115.7, 101. 4, 71.0, 70.8, 70.7, 70.3, 70.3, 69.7, 69.2, 69.0, 67.2, 61.4, 54.8, 54.6, 39.4, 38.1, 38.2, 20.9, 20.8, 20.80, 20.75
14b	7.98(s, 1H), 7.81(d, J=8.1 Hz, 1H), 7.61(d, J=7.9 Hz, 1H), 7.30—7.04(m, 11H), 6.94—6.86(m, 2H), 6.47(t, J=4.9 Hz, 1H), 5.38(d, J=3.3 Hz, 1H), 5.21(dd, J=10.5, 8.0 Hz, 1H), 5.04(dd, J=10.5, 3.4 Hz, 1H), 4.92—4.83(m, 1H), 4.69—4.59(m, 1H), 4.55(d, J=8.0 Hz, 1H), 4.21—4.07(m, 2H), 4.00—3.88(m, 2H), 3.77—3.67(m, 1H), 3.66—3.41(m, 7H), 3.40—3.29(m, 3H), 3.11(d, J=6.9 Hz, 2H), 3.00(d, J=7.0 Hz, 2H), 2.12(s, 3H), 2.03(s, 3H), 2.02(s, 3H), 1.98(s, 3H)	170.5, 170.4, 170.3,170.21, 170.16, 169.7, 165.6, 140.6, 136.4, 136.3, 136.2, 135.6, 130.1, 129.3, 128.6, 128.4, 127.0, 126.8, 126.2, 101.2, 94.1, 70.8, 70.6, 70.5, 70.1, 70.1, 69.5, 69.0, 68.8, 67.0, 61.2, 54.7, 54.5, 39.2, 38.6, 38.1, 20.8, 20.64, 20.61, 20.57
14c	7.61(d, J=8.6 Hz, 2H), 7.39(d, J=8.5 Hz, 2H), 7.20—7.07(m, 7H), 6.80(d, J=8.6 Hz, 2H), 6.71(d, J=7.3 Hz, 1H), 6.62(d, J=7.8 Hz, 1H), 6.37(t, J=4.9 Hz, 1H), 5.39(d, J=2.6 Hz, 1H), 5.22(dd, J=10.5, 8.0 Hz, 1H), 5.05(dd, J=10.5, 3.4 Hz, 1H), 4.80—4.68(m, 1H), 4.63—4.53(m, 2H), 4.23—4.08(m, 2H), 4.02—3.90(m, 4H), 3.77—3.67(m, 1H), 3.65—3.33(m, 10H), 3.10—3.05(m, 2H, 3a-H), 3.02(d, J=6.8 Hz, 2H), 2.13(s, 3H), 2.04(s, 3H), 2.03(s, 3H,), 1.99(s, 3H), 1.39(t, J=7.0 Hz, 3H)	170.61, 170.59, 170.41, 170.35,170.3, 169.8, 166.2, 158.2, 138.3, 136.6, 132.2, 130.5 129.4, 129.0, 128.7, 128.6, 128.0, 127.0, 114.9, 101.5, 71.0, 70.81, 70.75, 70.4, 70.3, 69.7, 69.3, 69.0, 67.2, 63.5, 61.4, 55.0, 54.6, 39.4, 38.5, 37.3, 21.0, 20.83, 20.80, 20.75, 15.0
14d	7.69(dd, J=8.8, 5.3 Hz, 2H), 7.31—7.05(m, 12H), 6.77(d, J=7.6 Hz, 2H), 6.43(t, J=4.3 Hz, 1H), 5.38(d, J=3.4 Hz, 1H,), 5.21(dd, J=10.5, 7.9 Hz, 1H), 5.05(dd, J=10.5, 3.4 Hz, 1H) 4.87—4.77(m, 1H), 4.63—4.55(m, 2H), 4.20—4.08(m, 2H), 3.98—3.90(m, 2H), 3.79—3.69(m, 1H), 3.66—3.43(m, 11H), 3.42—3.30(m, 3H), 3.13(d, J=6.9 Hz, 2H), 3.01(d, J=6.9 Hz, 2H), 2.13(s, 3H), 2.03(s, 3H), 2.02(s, 3H), 1.97(s, 3H)	170.63, 170.57, 170.41, 170.38,170.3, 169.7, 166.3, 166.2, 163.8, 136.6, 136.5, 129.98, 129.95, 129.7, 129.6, 129.4, 129.0, 128.6, 127.2, 126.9, 115.8, 115.6, 101.3, 71.0, 70.8, 70.7, 70.61, 70.58, 70.32, 70.29, 69.7, 69.1, 68.9, 67.2, 61.4, 54.8, 54.6, 39.4, 38.7, 38.2, 20.9, 20.80, 20.78, 20.75
Compd.	¹H NMR(400 MHz, CDCl₃), δ	¹³C NMR(100 MHz, CDCl₃), δ
14e	7.98(s, 1H), 7.81(d, J=8.1 Hz, 1H), 7.61(d, J=7.9 Hz, 1H), 7.30—7.04(m, 11H), 6.92(d, J=7.8 Hz, 2H), 6.49(t, J=5.0 Hz, 1H), 5.38(d, J=3.3 Hz, 1H), 5.20(dd, J=10.5, 8.0 Hz, 1H), 5.05(dd, J=10.5, 3.4 Hz, 1H), 4.91—4.82(m, 1H), 4.67—4.56(m, 2H), 4.20—4.07(m, 2H), 3.98—3.90(m, 2H), 3.77—3.69(m, 1H), 3.67—3.48(m, 10H), 3.48—3.29(m, 4H), 3.11(d, J=6.9 Hz, 2H), 3.01(dd, J=6.9, 1.5 Hz, 2H), 2.12(s, 3H), 2.03(s, 3H), 2.01(s, 3H), 1.97(s, 3H)	170.5, 170.4, 170.23, 170.21, 170.19, 169.5, 165.6, 140.5, 136.4, 136.3, 136.2, 135.7, 130.1, 129.3, 129.2, 128.7, 128.3, 127.0, 126.7, 126.3, 101.1, 94.1, 70.8, 70.5, 70.5, 70.41, 70.38, 70.12, 70.09, 69.4, 68.9, 68.8, 67.0, 61.2, 54.7, 54.4, 39.2, 38.6, 38.1, 20.7, 20.62, 20.60, 20.58
14f	7.63(d, J=8.7 Hz, 2H), 7.39(d, J=8.7 Hz, 2H), 7.19—7.06(m, 7H), 6.79(d, J=8.6 Hz, 2H), 5.39(dd, J=3.4, 1.0 Hz, 1H), 5.22(dd, J=10.5, 7.9 Hz, 1H), 5.06(dd, J=10.5, 3.4 Hz, 1H), 4.83—4.76(m, 1H), 4.65—4.57(m, 2H), 4.20—4.09(m, 2H), 4.01—3.92(m, 4H), 3.78—3.70(m, 1H), 3.67—3.29(m, 14H), 3.07(dd, J=6.7, 2.3 Hz, 2H), 3.02(d, J=6.9 Hz, 2H), 2.13(s, 3H), 2.05(s, 3H), 2.03(s, 3H), 1.98(s, 3H), 1.38(t, J=7.0 Hz, 3H)	170.7, 170.6, 170.39, 170.36, 170.3, 169.7, 166.2, 158.2, 138.2, 136.6, 132.2, 130.4, 129.4, 128.9, 128.7, 128.68, 128.1, 127.0, 114.8, 101.4, 71.0, 70.8, 70.7, 70.6, 70.6, 70.3, 70.3, 69.6, 69.1, 68.9, 67.2, 63.5, 61.4, 55.0, 54.6, 39.3, 38.6, 37.4, 20.9, 20.80, 20.78, 20.7, 15.0

Table 4 Appearance, yields, melting points, specific rotation, MS and IR data for the target compounds 15a—15f

Compd.	Appearance	Yield (%)	m.p./℃	[α $] D 20 a$ /(°) (c=0.5)	HRMS(calcd.)^b, m/z	IR(KBr), $ν ˙$ /cm^-1
15a	White solid	88	156—157	-80.73	750.3010(750.3014)	3283, 2880, 1634, 1542, 1507, 1076, 700
15b	White solid	89	168—169	-46.64	858.2074(858.2075)	3278, 2875, 1635, 1540, 1508, 1075, 698
15c	White solid	88	182—184	-36.09	810.3001(810.2981)	3284, 2924, 1632, 1542, 1512, 1073, 677
15d	White solid	74	151—152	-36.99	794.3265(794.3276)	3282, 2875, 1635, 1542, 1506, 1077, 699
15e	White solid	73	166—167	-39.71	902.2334(902.2337)	3273, 2873, 1635, 1534, 1506, 1077, 698
15f	White solid	78	186—189	-43.17	832.3429(832.3423)	3279, 2873, 1632, 1539, 1512, 1091, 702

Table 4 Appearance, yields, melting points, specific rotation, MS and IR data for the target compounds 15a—15f

Compd.	Appearance	Yield (%)	m.p./℃	[α $] D 20 a$ /(°) (c=0.5)	HRMS(calcd.)^b, m/z	IR(KBr), $ν ˙$ /cm^-1
15a	White solid	88	156—157	-80.73	750.3010(750.3014)	3283, 2880, 1634, 1542, 1507, 1076, 700
15b	White solid	89	168—169	-46.64	858.2074(858.2075)	3278, 2875, 1635, 1540, 1508, 1075, 698
15c	White solid	88	182—184	-36.09	810.3001(810.2981)	3284, 2924, 1632, 1542, 1512, 1073, 677
15d	White solid	74	151—152	-36.99	794.3265(794.3276)	3282, 2875, 1635, 1542, 1506, 1077, 699
15e	White solid	73	166—167	-39.71	902.2334(902.2337)	3273, 2873, 1635, 1534, 1506, 1077, 698
15f	White solid	78	186—189	-43.17	832.3429(832.3423)	3279, 2873, 1632, 1539, 1512, 1091, 702

Table 5 1H NMR and 13C NMR data for the target compounds 15a—15f

Compd.	¹H NMR(400 MHz, DMSO-d₆), δ	¹³C NMR(100 MHz, DMSO-d₆), δ
15a	8.55(d, J=8.4 Hz, 1H), 8.08(d, J=8.2 Hz, 1H), 8.01(t, J=5.5 Hz, 1H), 7.79(dd, J=8.7, 5.6 Hz, 2H), 7.29—7.06(m, 12H), 4.80(d, J=4.3 Hz, 1H), 4.69—4.59(m, 2H), 4.54(t, J=5.7 Hz, 1H), 4.47(dd, J=13.7, 8.3 Hz, 1H), 4.33(d, J=4.5 Hz, 1H), 4.05(d, J=7.0 Hz, 1H), 3.85—3.73(m, 1H), 3.62—3.09(m, 17H), 3.05—2.75(m, 4H)	171.1, 170.8, 165.2, 162.7, 138.3, 137.6, 130.4, 130.1, 130.0, 129.3, 129.2,128.07, 128.05, 126.3, 126.2, 115.3, 115.1, 103.6, 75.2, 73.5, 70.5, 69.78, 69.75, 69.7, 69.0, 68.2, 67.7, 60.5, 54.9, 54.0, 38.7, 37.9, 36.8
15b	8.64(d, J=8.5 Hz, 1H), 8.12—8.05(m, 2H), 8.01(t, J=5.6 Hz, 1H), 7.85(d, J=7.8 Hz, 1H), 7.71(d, J=7.9 Hz, 1H), 7.28—7.08(m, 11H), 4.80(d, J=4.4 Hz, 1H), 4.69—4.60(m, 2H), 4.54(t, J=5.6 Hz, 1H), 4.47(dd, J=13.6, 8.3 Hz, 1H), 4.33(d, J=4.5 Hz, 1H), 4.05(d, J=7.1 Hz, 1H), 3.85—3.75(m, 1H), 3.61—3.10(m, 17H), 3.06—2.76(m, 4H)	170.9, 170.8, 164.8, 139.9, 138.3, 137.6, 136.0, 135.8, 130.5, 129.3, 129.1, 128.1, 128.0, 126.9, 126.3, 103.6, 94.6, 75.2, 73.5, 70.5, 69.8, 69.7, 69.0, 68.2, 67.7, 60.5, 54.8, 54.0, 38.7, 37.9, 36.8
15c	8.58(d, J=8.4 Hz, 1H), 8.10(d, J=8.0 Hz, 1H), 8.01(t, J=5.7 Hz, 1H), 7.77(d, J =8.7 Hz, 2H), 7.52(d, J=8.7 Hz, 2H, 7.21—7.10(m, 7H), 6.75(d, J=8.7 Hz, 2H), 4.81(d, J=4.5 Hz, 1H), 4.68(d, J=5.2 Hz), 4.63—4.56(m, 1H), 4.55(t, J=5.7 Hz, 1H), 4.52—4.48(m,	171.3, 171.0, 165.4, 157.2, 137.8, 136.4, 132.9, 130.3, 130.2, 129.6, 129.5, 128.5, 128.2, 126.5, 114.1, 103.8, 75.4, 73.7, 70.7,69.98, 69.94,
Compd.	¹H NMR(400 MHz, DMSO-d₆), δ	¹³C NMR(100 MHz, DMSO-d₆), δ
15c	1H), 4.34(d, J=4.5 Hz, 1H), 4.07(d, J=7.3 Hz, 1H), 3.91(q, J=7.0 Hz, 2Ha), 3.85—3.77(m, 1H), 3.62—3.58(m, 1H), 3.57—3.44(m, 11H), 3.39—3.10(m, 4H), 2.99—2.91(m, 2H), 2.82(dd, J=13.8, 9.4 Hz, 2H), 1.25(t, J=7.0 Hz, 3H)	69.9, 69.2, 68.4, 67.9, 63.0, 60.7, 55.3, 54.2, 39.9, 38.6, 37.9, 36.1
15d	7.74(dd, J=8.7, 5.4 Hz, 2H), 7.30—7.08(m, 12H), 4.79(dd, J=9.4, 5.7 Hz, 1H), 4.60(t, J=7.3 Hz, 1H), 4.24(d, J=7.5 Hz, 1H), 4.02—3.95(m, 1H), 3.83—3.22(m, 21H), 3.21—3.05(m, 2H), 3.03—2.85(m, 2H)	173.3, 173.1, 169.0, 167.5, 165.0, 138.6, 138.2, 131.5, 131.2, 131.1, 130.4, 130.3, 129.5, 129.4, 127.8, 116.4, 116.2, 105.1, 76.7, 74.9, 72.5, 71.6, 71.5, 71.3, 70.4, 70.3, 69.6, 62.5, 56.6, 56.0, 40.4, 39.2, 38.4
15e	8.01(s, 1H), 7.87(d, J=8.0 Hz, 1H), 7.65(d, J=8.2 Hz, 1H), 7.28—7.10(m, 11H), 4.79(dd, J=9.4, 5.6 Hz, 1H, 2-H), 4.61(dd, J=8.1, 6.3 Hz, 1H,), 4.24(d, J=7.5 Hz, 1H), 4.03—3.96(m, 1H), 3.85—3.23(m, 21H), 3.21—3.07(m, 2H), 3.01—2.87(m, 2H)	173.2, 173.1, 168.4, 141.8, 138.6, 138.2, 137.6, 137.2, 131.3, 130.4, 130.3, 129.5, 129.5, 127.8, 105.1, 94.6, 76.7, 74.9, 72.5,71.54, 71.48, 71.3, 70.4, 70.3, 69.6, 62.5, 56.6, 56.0, 40.4, 39.2, 38.3
15f	8.60(d, J=8.4 Hz, 1H), 8.12(d, J=8.0 Hz, 1H), 8.02(t, J=5.4 Hz, 1H), 7.79(d, J=8.6 Hz, 2H), 7.53(d, J=8.6 Hz, 2H), 7.24—7.12(m, 7H), 6.77(d, J=8.6 Hz, 2H), 4.83(d, J=4.4 Hz, 1H), 4.70(d, J=5.0 Hz, 1H), 4.66—4.45(m, 3H), 4.36(d, J=4.6 Hz, 1H), 4.08(d, J=7.0 Hz, 1H), 3.93(q, J=7.0 Hz, 2H), 3.88—3.55(m, 2H), 3.59—3.10(m, 20H), 3.03—2.92(m, 2H), 2.90—2.79(m, 2H), 1.27(t, J=7.0 Hz, 3H)	171.0, 170.7, 165.2, 157.0, 137.5, 136.2, 136.0, 132.7, 130.1, 129.9, 129.3, 129.2, 128.3, 128.0, 126.3, 113.9, 103.6, 75.2, 73.5, 70.5, 69.8, 69.7, 69.6, 68.9, 68.2, 67.7, 62.8, 60.4, 55.1, 54.0, 38.6, 37.9, 36.0, 14.7

Table 5 1H NMR and 13C NMR data for the target compounds 15a—15f

Compd.	¹H NMR(400 MHz, DMSO-d₆), δ	¹³C NMR(100 MHz, DMSO-d₆), δ
15a	8.55(d, J=8.4 Hz, 1H), 8.08(d, J=8.2 Hz, 1H), 8.01(t, J=5.5 Hz, 1H), 7.79(dd, J=8.7, 5.6 Hz, 2H), 7.29—7.06(m, 12H), 4.80(d, J=4.3 Hz, 1H), 4.69—4.59(m, 2H), 4.54(t, J=5.7 Hz, 1H), 4.47(dd, J=13.7, 8.3 Hz, 1H), 4.33(d, J=4.5 Hz, 1H), 4.05(d, J=7.0 Hz, 1H), 3.85—3.73(m, 1H), 3.62—3.09(m, 17H), 3.05—2.75(m, 4H)	171.1, 170.8, 165.2, 162.7, 138.3, 137.6, 130.4, 130.1, 130.0, 129.3, 129.2,128.07, 128.05, 126.3, 126.2, 115.3, 115.1, 103.6, 75.2, 73.5, 70.5, 69.78, 69.75, 69.7, 69.0, 68.2, 67.7, 60.5, 54.9, 54.0, 38.7, 37.9, 36.8
15b	8.64(d, J=8.5 Hz, 1H), 8.12—8.05(m, 2H), 8.01(t, J=5.6 Hz, 1H), 7.85(d, J=7.8 Hz, 1H), 7.71(d, J=7.9 Hz, 1H), 7.28—7.08(m, 11H), 4.80(d, J=4.4 Hz, 1H), 4.69—4.60(m, 2H), 4.54(t, J=5.6 Hz, 1H), 4.47(dd, J=13.6, 8.3 Hz, 1H), 4.33(d, J=4.5 Hz, 1H), 4.05(d, J=7.1 Hz, 1H), 3.85—3.75(m, 1H), 3.61—3.10(m, 17H), 3.06—2.76(m, 4H)	170.9, 170.8, 164.8, 139.9, 138.3, 137.6, 136.0, 135.8, 130.5, 129.3, 129.1, 128.1, 128.0, 126.9, 126.3, 103.6, 94.6, 75.2, 73.5, 70.5, 69.8, 69.7, 69.0, 68.2, 67.7, 60.5, 54.8, 54.0, 38.7, 37.9, 36.8
15c	8.58(d, J=8.4 Hz, 1H), 8.10(d, J=8.0 Hz, 1H), 8.01(t, J=5.7 Hz, 1H), 7.77(d, J =8.7 Hz, 2H), 7.52(d, J=8.7 Hz, 2H, 7.21—7.10(m, 7H), 6.75(d, J=8.7 Hz, 2H), 4.81(d, J=4.5 Hz, 1H), 4.68(d, J=5.2 Hz), 4.63—4.56(m, 1H), 4.55(t, J=5.7 Hz, 1H), 4.52—4.48(m,	171.3, 171.0, 165.4, 157.2, 137.8, 136.4, 132.9, 130.3, 130.2, 129.6, 129.5, 128.5, 128.2, 126.5, 114.1, 103.8, 75.4, 73.7, 70.7,69.98, 69.94,
Compd.	¹H NMR(400 MHz, DMSO-d₆), δ	¹³C NMR(100 MHz, DMSO-d₆), δ
15c	1H), 4.34(d, J=4.5 Hz, 1H), 4.07(d, J=7.3 Hz, 1H), 3.91(q, J=7.0 Hz, 2Ha), 3.85—3.77(m, 1H), 3.62—3.58(m, 1H), 3.57—3.44(m, 11H), 3.39—3.10(m, 4H), 2.99—2.91(m, 2H), 2.82(dd, J=13.8, 9.4 Hz, 2H), 1.25(t, J=7.0 Hz, 3H)	69.9, 69.2, 68.4, 67.9, 63.0, 60.7, 55.3, 54.2, 39.9, 38.6, 37.9, 36.1
15d	7.74(dd, J=8.7, 5.4 Hz, 2H), 7.30—7.08(m, 12H), 4.79(dd, J=9.4, 5.7 Hz, 1H), 4.60(t, J=7.3 Hz, 1H), 4.24(d, J=7.5 Hz, 1H), 4.02—3.95(m, 1H), 3.83—3.22(m, 21H), 3.21—3.05(m, 2H), 3.03—2.85(m, 2H)	173.3, 173.1, 169.0, 167.5, 165.0, 138.6, 138.2, 131.5, 131.2, 131.1, 130.4, 130.3, 129.5, 129.4, 127.8, 116.4, 116.2, 105.1, 76.7, 74.9, 72.5, 71.6, 71.5, 71.3, 70.4, 70.3, 69.6, 62.5, 56.6, 56.0, 40.4, 39.2, 38.4
15e	8.01(s, 1H), 7.87(d, J=8.0 Hz, 1H), 7.65(d, J=8.2 Hz, 1H), 7.28—7.10(m, 11H), 4.79(dd, J=9.4, 5.6 Hz, 1H, 2-H), 4.61(dd, J=8.1, 6.3 Hz, 1H,), 4.24(d, J=7.5 Hz, 1H), 4.03—3.96(m, 1H), 3.85—3.23(m, 21H), 3.21—3.07(m, 2H), 3.01—2.87(m, 2H)	173.2, 173.1, 168.4, 141.8, 138.6, 138.2, 137.6, 137.2, 131.3, 130.4, 130.3, 129.5, 129.5, 127.8, 105.1, 94.6, 76.7, 74.9, 72.5,71.54, 71.48, 71.3, 70.4, 70.3, 69.6, 62.5, 56.6, 56.0, 40.4, 39.2, 38.3
15f	8.60(d, J=8.4 Hz, 1H), 8.12(d, J=8.0 Hz, 1H), 8.02(t, J=5.4 Hz, 1H), 7.79(d, J=8.6 Hz, 2H), 7.53(d, J=8.6 Hz, 2H), 7.24—7.12(m, 7H), 6.77(d, J=8.6 Hz, 2H), 4.83(d, J=4.4 Hz, 1H), 4.70(d, J=5.0 Hz, 1H), 4.66—4.45(m, 3H), 4.36(d, J=4.6 Hz, 1H), 4.08(d, J=7.0 Hz, 1H), 3.93(q, J=7.0 Hz, 2H), 3.88—3.55(m, 2H), 3.59—3.10(m, 20H), 3.03—2.92(m, 2H), 2.90—2.79(m, 2H), 1.27(t, J=7.0 Hz, 3H)	171.0, 170.7, 165.2, 157.0, 137.5, 136.2, 136.0, 132.7, 130.1, 129.9, 129.3, 129.2, 128.3, 128.0, 126.3, 113.9, 103.6, 75.2, 73.5, 70.5, 69.8, 69.7, 69.6, 68.9, 68.2, 67.7, 62.8, 60.4, 55.1, 54.0, 38.6, 37.9, 36.0, 14.7

Scheme 2 Synthetic route 2 for intermediate 5a

Table 6 Inhibition ratios for the replication of HBV DNA of compounds 15a—15f*

Compd.	Inhibition ratio(%)
Compd.	12.5 μg/mL	25 μg/mL	50 μg/mL
15a	19.08±0.71	40.61±2.13	43.88±0.55
15b	65.57±2.41	70.27±7.73	72.24±2.07
15c	29.89±1.68	25.60±1.04	56.49±0.73
15d	16.48±3.66	29.19±1.90	41.28±1.63
15e	11.04±0.19	12.54±2.60	33.05±1.00
15f	25.07±0.73	16.97±1.12	65.24±2.23
Lamivudine			92.57±1.03

References 28

[1]	Li G. , Viral Hepatitis , People’s Medical Publishing House, Beijing, 2002, 22— 41
	( 李刚. 病毒性肝炎, 北京: 人卫出版社, 2002, 22— 41)
[2]	Zoulim, F. , Liver Int., 2013, 31( S1), 111- 116 doi: 10.1111/liv.12069 URL pmid: 23286855
[3]	Feng D., R. , Liang, S. , Wang Y., Y. , Xu Y., J. , Chem. Res. Chinese Universities, 2014, 30( 5), 749- 754 doi: 10.1016/j.biomaterials.2014.03.014 URL pmid: 24685267
[4]	Pardo, M. , Bartolome, J. , Carreno, V. , Arch. Med. Res., 2007, 38( 6), 661- 677 doi: 10.1016/j.arcmed.2006.12.013 URL pmid: 17613358
[5]	刘玉明, 梁光义, 徐必学. 天然产物研究与开发, 2003, 15( 1), 15- 17 doi: 10.3969/j.issn.1001-6880.2003.01.005 URL
	Liu Y., M. , Liang G., Y. , Xu B., X. , Nat. Prod. Res. Dev., 2003, 15( 1), 15- 17 doi: 10.3969/j.issn.1001-6880.2003.01.005 URL
[6]	Xu B., X. , Huang Z., M. , Liu C., X. , Cai Z., G. , Pan W., D. , Cao P., X. , Hao X., J. , Liang G., Y. , Bioorg. Med. Chem., 2009, 17( 8), 3118- 3125
[7]	Qiu J., Y. , Xu B., X. , Huang Z., M. , Pan W., D. , Cao P., X. , Liu C., X. , Hao X., J. , Song B. A.. Liang G., Y. , Bioorg. Med. Chem., 2011, 19( 18), 5352- 5360
[8]	邱净英, 黄正明, 潘卫东, 曹佩雪, 梁光义. 中国药科大学学报, 2012, 43( 5), 390- 394
	Qiu J., Y. , Huang Z., M. , Pan W., D. , Cao P., X. , Liang G., Y. , J. Chin. Pharm. Univ., 2012, 43( 5), 390- 394
[9]	梁光平, 胡占兴, 刘青川, 黄正明, 张建新, 梁光义, 徐必学. 高等学校化学学报, 2014, 35( 11), 2353- 2359 doi: 10.7503/cjcu20140223
	Liang G., P. , Hu Z., X. , Liu Q., C. , Huang Z., M. , Zhang J., X. , Liang G., Y. , Xu B., X. , Chem. J. Chinese Universities, 2014, 35( 11), 2353- 2359 doi: 10.7503/cjcu20140223
[10]	Ashwell, G. , Harford, J. , Annu. Rev. Biochem., 1982, 51( 4), 531- 554
[11]	Morell A., G. , Gregoriadis, G. , Scheinberg I., H. , Hickman, J. , Ashwell, G. , J. Biol. Chem., 1971, 246( 5), 1461- 1467
[12]	Steirer L., M. , Park E., I. , Townsend R., R. , Jacques U., B. , J. Biol. Chem., 2009, 284( 6), 3777- 3783 doi: 10.1074/jbc.M808689200 URL pmid: 19075021
[13]	Hashida, M. , Nishikawa, M. , Takakura, Y. , J. Controlled Release, 1995, 36( 12), 99- 107 doi: 10.1016/0168-3659(95)00050-I URL
[14]	Wang Y., Q. , Su, J. , Cai W., W. , Lu, P. , Yuan L., F. , Jin, T. , Chen S., Y. , Sheng, J. , Drug, Design , Development and Therapy, 2013, 7( 3), 211- 221
[15]	吴卫, 程怡, 吴琼. 南京医科大学学报, 2012, 32( 2), 168- 171 doi: 10.7655 URL
	Wu, W. , Cheng, Y. , Wu, Q. , J. Nanjing. Med. Univ., 2012, 32( 2), 168- 171 doi: 10.7655 URL
[16]	吴超, 郭伟英. 辽宁医学院学报, 2008, 29( 6), 490- 491 doi: 10.3969/j.issn.1674-0424.2008.06.004 URL
	Wu, C. , Guo W., Y. , J. Liaoning Med. Univ., 2008, 29( 6), 490- 491 doi: 10.3969/j.issn.1674-0424.2008.06.004 URL
[17]	袁洁, 刘青川, 徐广灿, 胡占兴, 梁光平, 黄正明, 刘昌孝, 梁光义, 徐必学. 有机化学, 2015, 35( 10), 2176- 2183 doi: 10.6023/cjoc201505011
	Yuan, J. , Liu Q., C. , Xu G., C. , Hu Z., X. , Liang G., P. , Huang Z., M. , Liu C., X. , Liang G., Y. , Xu B., X. , Chin. J. Org. Chem., 2015, 35( 10), 2176- 2183 doi: 10.6023/cjoc201505011
[18]	Lee Y., C. , Lee R., T. , Carbohydrates in Chemistry and, Biology , Wiley-VCH, Weinheim, 2000, 549-592
[19]	Biessen E., A. , Beuting D., M. , Roelen H., C. , Marel G. A. V., D. , Boom J. H., V. , Berkel T. J., V. , J. Med. Chem., 1995, 38( 9), 1538- 1546
[20]	Dean, B. , Oguchi, H. , Cai, S. , Otsuji, E. , Tashiro, K. , Hakomori, S. , Toyokuni, T. , Carbohydr. Res., 1993, 245( 2), 175- 192 doi: 10.1016/0008-6215(93)80071-L URL pmid: 8370021
[21]	徐广灿, 刘青川, 袁洁, 胡占兴, 马芳芳, 梁光义, 徐必学. 有机化学, 2016, 36( 7), 1617- 1625 doi: 10.6023/cjoc201512051
	Xu G., C. , Liu Q., C. , Yuan, J. , Hu Z., X. , Ma F., F. , Liang G., Y. , Xu B., X. , J. Org. Chem., 2016, 36( 7), 1617- 1625 doi: 10.6023/cjoc201512051
[22]	Percec, V. , Leowanawat, P. , Sun H., J. , Kulikov, O. , Nusbaum C., D. , Tran T., M. , Bertin, A. , Wilson D., A. , Peterca, M. , Zhang S., D. , Kamat N., P. , Vargo, K. , Moock, D. , Johnston E., D. , Hammer D., A. , Pochan D., J. , Chen Y., X. , Chabre Y., M. , Shiao T., C. , Bergeron-Blerk, M. , André, S. , Roy, R. , Gabius H., J. , Heiney P., A. , J. Am. Chem. Soc., 2013, 135( 24), 9055- 9077
[23]	Zhang S., D. , Moussodia R., O , Sun H., J. , Leowanawat, P. , Muncan, A. , Nusbaum C., D. , Chelling K., M. , Heiney P., A. , Klein M., L. , Andre, S. , Roy, R. , Gabius H., J. , Perec, V. , Angew. Chem. Int. Ed., 2014, 53( 41), 10899- 10903
[24]	Ligeour, C. , Dupin, L. , Marra, A. , Eur. J. Org. Chem., 2014, 2014( 34), 7621- 7630 doi: 10.1002/ejoc.201402902 URL
[25]	Li Y., X. , Wang F., J. , Chen, W. , Wan Y., Y. , Li Z., M. , Chem. Res. Chinese Universities, 2015, 31( 6), 952- 957
[26]	Alker, D. , Arrowsmith J., E. , Eur. J. Med. Chem., 1991, 26( 91), 907- 913 doi: 10.1016/0223-5234(91)90132-7 URL
[27]	Chen, N. , Xie, J. , J. Org. Chem., 2014, 79( 21), 10716- 10724 doi: 10.1021/jo502128h URL pmid: 25318074
[28]	Cai M. S., Li Z. J., Carbohydrate Chemistry: Fundamentals, Reactions, Synthesis, Isolation and Structure, Chemical Industry Press, Beijing, 2006, 370— 373
	( 蔡孟深, 李中军. 糖化学基础、反应、合成、分离及结构 , 北京: 化学工业出版社, 2006, 370— 373)