新型N-甲基马蹄金素衍生物的合成及抗乙肝病毒活性

Synthesis and Anti-HBV Activities of Novel N-methylated Derivatives of MTS

以L-苯丙氨酸甲酯盐酸盐为原料,依次经缩合、还原、甲基化和催化氢化反应制得N-甲基-L-苯丙氨醇(4); 4依次与N-Fmoc-L-苯丙氨酸(5a)或N-Fmoc-L-酪氨酸(5b)经缩合和脱Fmoc反应制得游离氨基化合物7a或7b;7a(7b)与多种苯甲酸衍生物反应合成了20个新型的N-甲基马蹄金素衍生物(8a～8t),其结构经~1H NMR,^(13)C NMR和MS(ESI)表征。以2.2.15细胞模型进行了初步的抗乙肝病毒(HBV)活性评价。结果表明:化合物8n和8o显示出一定的抗HBV活性,IC_(50)分别为52.5μmol·L^(-1)和49.2μmol·L^(-1)。

Staring from L-phenylalanine methyl ester hydrochloride, N -methyl-L-phenylalaninol( 4 ) was synthesized by a four-step reaction of condensation, reduction, methylation and hydrogenation. Condensation of 4 with N -Fmoc-L-phenylalanine( 5a ) or N -Fmoc-L-tyrosine( 5b ) provided 6a and 6b , respectively. Deprotection of the Fmoc group of 6a and 6b provided intermediates 7a and 7b , respectively. Condensation of 7a or 7b with different derivatives of benzoic acid provided twenty novel N -methyl derivatives of MTS( 8a^8t ). The structures were characterized by ^1H NMR,^13C NMR and MS(ESI). The anti-HBV activities of 8a^8t were evaluated in 2.2.15 cells model. The results showed that 8n and 8o exhibited anti-HBV activities with IC 50 of 52.5 μmol·L^-1 and 49.2 μmol·L^-1 , respectively.