Abstract

The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (5) and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (7), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance (NMR) from ¹H, ¹³C, APT, COSY, HSQC, and HMBC spectra. Additional HOMO-LUMO DFT calculations corroborated the NMR results and pointed to the most stable stereoisomers of each compound. Besides, further docking and molecular dynamic studies suggest that the stereoisomers (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, and 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione of these compounds may act as DNA intercalators and qualify as potential leads for the development of new anticancer drugs.

Communicated by Ramaswamy H. Sarma

摘要

化合物7-氯-9-(2-羟基-4,4-二甲基-6-氧代环己-1-烯-1-基)-3,3-二甲基-2,3,4,9-四氢-1H- xanthen-1-one ( 5 ) 和 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1 ,3-diazinane-2,4,6-trione ( 7 ) 由二甲酮和巴比妥酸合成，并通过核磁共振 (NMR) 从¹ H, ¹³获得了它们的三维结构和精确的化学位移分配C、APT、COSY、HSQC 和 HMBC 光谱。额外的 HOMO-LUMO DFT 计算证实了 NMR 结果，并指出了每种化合物最稳定的立体异构体。此外，进一步的对接和分子动力学研究表明立体异构体 (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-二甲基-2,3,4,9-四氢-1H-xanthen-1-one 和 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[这些化合物中的 2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione 可以作为 DNA 嵌入剂，并有资格作为开发新抗癌药物的潜在线索。

由 Ramaswamy H. Sarma 交流