6-氟-4-羟基-3-氧代-3,4-二氢喹喔啉-1(2H)-羧酸叔丁酯的合成、晶体结构及抗肿瘤活性研究

摘要/Abstract

摘要： 喹喔啉类化合物由于具有显著的生物活性而被广泛应用于医药、化工领域,特别是抗癌药物研发领域。本文通过四步反应法首次合成了6-氟-4-羟基-3-氧代-3,4-二氢喹喔啉-1(2H)-羧酸叔丁酯,经溶液结晶法获得其单晶体。晶体学分析表明,该化合物属单斜晶系,空间群C2/c,晶胞常数a=1.286 63(10) nm,b=2.252 49(17) nm,c=1.015 64(7) nm,Z=8,ρ_c＝1.359 g·cm^-3,R=0.053 8,R_w=0.140 6。在B3LYP/6-311+G(2d, p)模式下使用密度泛函理论(DFT)计算了该化合物的最佳结构,与X射线单晶衍射确定的晶体结构基本一致。抗肿瘤活性研究表明其有良好的抗肿瘤作用。此外,通过DFT计算了分子的静电势和前沿分子轨道。

关键词: 喹喔啉类化合物, 6-氟-4-羟基-3-氧代-3,4-二氢喹喔啉-1(2H)-羧酸叔丁酯, 晶体结构, 密度泛函理论, 合成, 抗肿瘤活性

Abstract: Quinoxaline compounds are widely used in the fields of medicine and chemical industry, especially in the development of anticancer drugs, due to their significant biological activity. 6-fluoro-4-hydroxy-3-oxo-3,4-dihydroquinoline-1 (2H)-carboxylic acid tert-butyl ester was synthesized through a four-step reaction method in this paper, and its single crystal was obtained by solution crystallization method. Crystallographic analysis indicates that the compound belongs to monoclinic crystal system with space group C2/c, the unit cell dimensions are a=1.286 63(10) nm, b=2.252 49(17) nm, c=1.015 64(7) nm, Z=8, ρ_c=1.359 g·cm^-3, R=0.053 8, R_w=0.140 6. The optimal structure was calculated using density functional theory (DFT) in B3LYP/6-311+G (2d, p) mode. The results are basically consistent with those obtained by X-ray single crystal diffraction. The antitumor activity study shows that the compound has good antitumor effect. In addition, the electrostatic potential and frontier molecular orbitals of the molecules were calculated by DFT to further understand their physical and chemical properties.

Key words: quinoxaline compound, 6-fluoro-4-hydroxy-3-oxo-3,4-dihydroquinoxalin-1 (2H)-carboxylic acid tert-butyl ester, crystal structure, density functional theory, synthesis, antitumor activity

中图分类号:

TQ225.2

毛云虹, 赵春深. 6-氟-4-羟基-3-氧代-3,4-二氢喹喔啉-1(2H)-羧酸叔丁酯的合成、晶体结构及抗肿瘤活性研究[J]. 人工晶体学报, 2024, 53(7): 1257-1268.

MAO Yunhong, ZHAO Chunshen. Synthesis, Crystal Structure and Antitumor Activity of 6-Fluoro-4-Hydroxy-3-Oxo-3,4-Dihydroquinoxaline-1 (2H)-Carboxylic Acid Tert-Butyl Ester[J]. JOURNAL OF SYNTHETIC CRYSTALS, 2024, 53(7): 1257-1268.

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