一种氨基葡萄糖棉酚Schiff碱衍生物的制备及其抗HIV-1病毒活性

摘要

目的: 确定1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱结构及其优势构象,并探讨其抗HIV-1病毒活性.方法: 制备1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱, 并利用红外光谱, 核磁波谱技术和PM6半经典计算等方法对其结构进行解析;采用HIV-lIIIB/TZM-bl细胞指示系统测定其抗HIV-1病毒活性.结果: 光谱分析表明1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱新化合物具有烯胺-烯胺结构特征,并归属了所有碳原子和氢质子化学位移;PM6研究表明1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱烯胺-烯胺和亚胺-亚胺构型的生成热分别为-4 168.415 kJ·mol-1和-4 150.080 kJ·mol-1,烯胺-烯胺构型在能量上更有利,并确立了其优势构象,分子内氢键使其更为稳定,与光谱分析结果一致;新化合物显示了较强的抗艾滋病毒活性,可能作用在病毒感染细胞的进入阶段.结论: 1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱以烯胺-烯胺构型存在,具有一定抗艾滋病毒活性.%Objective: To confirm the structure and preferential conformation of the Schiff base of gossypol with 1, 3, 4, 6-tetra-O-acetyl-β-D-glucosamine and explore its anti-HIV-1 activity.Methods: The Schiff base of gossypol with 11, 3, 4, 6-tetra-O-acetyl-β-D-glucosamine was synthesized and identified by FT-IR, NMR spectroscopy and the PM6 semi-classical calculation.The inhibitory activity of the novel compound against the laboratory-adapted HIV-1IIIB strain was examined using the HIV-1IIIB/TZM-bl indicator cell culture system.Results: The 1H and 13C-NMR signals of the new Schiff base were assigned.The PM6 semi-classical calculation indicated that enamine-enamine tautomeric form of the new Schiff base was more stable,which was stabilized by the intramolecular hydrogen bonds.The anti-HIV-1 test showed that the compound could block the entry of HIV-1IIIB into the target cells.Conclusion: The Schiff base of gossypol with 1, 3, 4, 6-tetra-O-acetyl-β-D-glucosamine exhibits enamine-enamine tautomeric form in solution, which shows potential anti-HIV-1 activity.