寡肽手性膦酸酯硫脲的合成及其抗烟草花叶病毒活性

为了寻找新型具有抗烟草花叶病毒 (TMV) 作用的化合物，在前期研究工作基础上，以取代苄胺、氨基酸及亚膦酸二烷基酯等为原料，按照由C端向N端依次接肽的合成策略，采用缩合剂O-苯并三氮唑-四甲基脲六氟膦酸酯 (HBTU) 合成酰胺的方法，获得了18个新型寡肽手性膦酸酯硫脲，其结构均经红外光谱、(1H、13C、31P、19F) NMR及元素分析确证和表征，并首次研究了该类化合物抗TMV活性。结果表明:部分目标物对TMV具有较高治疗作用，其中化合物 5i 、 5j 和 5p 在500 μg/mL时对TMV侵染的活体治疗作用效果分别为52.6%、55.7%和56.1%，接近对照药剂宁南霉素 (55.4%)。值得进一步结构改造和构型优化，并在此基础上进行作用机制研究。

Synthesis and anti-tobacco mosaic virus activity of oligopeptide chiral thioureas containing phosphonate moiety

In order to develop more effective anti-tobacco mosaic virus (TMV) agents, 18 noval oligopeptide chiral thioureas containing phosphonate moiety have been synthesized. Substituted benzylamines, amino acids and dialkyl phosphonate were employed as the starting materials. C-to-N synthesis strategy and coupling reagent O-benzotriazole-N,N,N'',N''-tetramethylurea(HBTU) were used. The structures of the target compounds were characterized by IR, (¹H, ¹³C, ³¹P, ¹⁹F) NMR and elemental analysis. The Anti-TMV activities of target compounds were evaluated for the first time. The results indicate that these compounds have a high therapeutic effect on TMV, and exhibit good anti-plant virus activities. The curative rates of 5i, 5j and 5p against TMV were 52.6%, 55.7% and 56.1%, respectively, which were comparable to the curative rate (55.4%) of the commercial reference ningnanmycin.