脱氢枞酸酰胺基-3, 4-二氢嘧啶酮衍生物的合成与抗病毒活性研究

doi:10.3969/j.issn.0253-2417.2019.02.007

Abstract

Abstract:

Dehydroabietic acid chloride was prepared via the reaction of dehydroabietic acid and thionylchloride, dehydroabietic acid acylthiosemicarbazide was synthesized by thiosemicarbazone and dehydroabietic acid chloride, followed by the reaction of dehydroabietic acid acylthiosemicarbazide, aromatic aldehydes with ethyl acetate to obtain ten dehydroabietic acid amide derived 3, 4-dihydropyrimidinones: 4-phenyl-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3a), 4-(4-methoxyphenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-di-hydropyrimidine-2-thione (3b), 4-(2-methoxyphenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimi-dine-2-thione (3c), 4-(4-methylphenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3d), 4-(4-bromophenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3e), 4-(4-p-tri-fluoromethylphenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3f). 4-(4-chlorophen-yl)-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3g), 4-(2, 6-dichlorophenyl)- 6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3h), 4-(2-nitrophenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-dihydropyrimidine-2-thione (3i), 4-(3-nitrophenyl)-6-methyl-1-dehydroabietic acid amide-3, 4-di-hydropyrimidine-2-thione (3j).The target compounds were characterized by FT-IR, MS, ¹H NMR and ¹³C NMR. The cytotoxicity of these 3, 4-dihydropyrimidinone derivatives (compounds 3a-3j) were tested with monkey embryonic kidney cells (MA-104 cells). The antiviral activities against the Herpes simplex virus type Ⅰ (HSV-1) of these derivatives were further evaluated with methyl thiazolyl tetrazolium(MTT) method. The results indicated that the cytotoxicity of these derivatives kept in a low level, compounds 3a, 3b, 3d, 3e, 3h, 3i and 3j showed lower cytotoxicity than the drug ribavirin; compound 3j performed better inhibitory activity of HSV-1(50% inhibitory concentration(IC₅₀) 0.465 g/L, selective index(SI)12.18) which was similar to ribavirin (IC₅₀=0.156 g/L, SI=12.6), and the other compounds showed weak inhibitory activity of HSV-1.

Key words: rosin, dehydroabietic acid, 3, 4-dihydropyrimidinone, antiviral activity

CLC Number:

TQ35
O621.3

Yunlong LUO,Minggui SHEN,Zhaosheng CAI,Shibin SHANG,Zhanqian SONG. Synthesis and Antiviral Activity Evaluation of Dehydroabietic Acid Amide Derived 3, 4-Dihydropyrimidinthiones[J]. Chemistry and Industry of Forest Products, 2019, 39(2): 46-52.

Figures/Tables 3

References 10

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编号 No.	溶剂 solvent	催化剂用量/% catalyst dosage	分离产率/% yield
1	H₂O	10	35
2	乙腈 acetonitrile	10	51
3	四氢呋喃 tetrahydrofuran	10	41
4	1, 4-二氧六环 1, 4-dioxane	10	40
5	甲苯 toluene	10	27
6	甲醇 methanol	10	78
7	乙醇 ethanol	0	—
8	乙醇 ethanol	5	75
9	乙醇 ethanol	10	82

化合物 compound	半数毒性质量浓度(TC₅₀)/(g·L^-1) 50% toxic concentration	半数抑制浓度(IC₅₀)/(g·L^-1) 50% inhibitory concentration	选择指数(SI) selective index
3a	5.193	2.099	2.474
3b	3.201	1.286	2.489
3c	0.368	0.392	0.939
3d	3.365	2.153	1.563
3e	2.922	0.676	4.322
3f	1.207	0.378	3.193
3g	1.148	0.362	3.171
3h	2.421	1.101	2.198
3i	2.192	1.018	2.1530
3j	5.664	0.465	12.180
利巴韦林 Ribavirin	1.967	0.156	12.600

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Synthesis and Antiviral Activity Evaluation of Dehydroabietic Acid Amide Derived 3, 4-Dihydropyrimidinthiones

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