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

Synthesis and Anti-HIV-1 Activity of One Schiff Base Derivative with Glucosamine of Gossypol

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-l_(ⅢB)/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 k J·mol^(-1)和-4 150.080 k J·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-glueosamine and explore its anti-HIV-1 activity. Methods： The Schiff base of gossypol with 11, 3, 4, 6-tetra-O-acetyl- β-D-glueosamine 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-1 mB/TZM-bl indicator eeU culture system. Results ： The ^1H and ^13 C-NMR signals of the new Schiff base were assigned. The PM6 semi-classical calculation indicated that enamine-enamine tautomeric form of the new Sehiff 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 ceils. 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.