| Coumarin compounds have diverse biological activities such as anti-tumor, anti-bacterial, anti-coagulant, anti-viral, anti-inflammatory, anti-vascular sclerosis, especially in terms of anti-bacterial activity. A large number of1,2,3-triazole compounds have been found to have potential anti-bacterial, analgesic, anti-inflammatory, anti-spasmodic, anti-tumor, anti-viral and anti-cancer activity. Steroid drugs are commonly used in anti-HIV, anti-cancer, anti-infection and in the treatment of rheumatism and cardiovascular. In this paper, using the combination of drug design principles, the naphthol coumarins are connected with triazole and steroids, which may have good biological activity such as anti-bacterial activity.First, with two different naphtholes as the raw materials, several kinds of4-azido-naphtholmethyl coumarins were synthesized from4-chloroethyl-acetoacetate by means of Pechmann reaction with methane-sulfonic acid as a Lewis acid catalyst under solvent-free conditions and at room temperature. The times were less than1h, and the average reaction yield is above60.0%. Then the obtained products were used to react with sodium azide in acetone solvent to afford4-azidomethyl-naphthol coumarin by means of Nucleophilic substitution reaction. In this reaction system, no additional catalyst was added. Because sodium azide, as a strong base, was both the catalyst and the reactant, which can ensure the smooth progress of the Nucleophilic substitution reaction. And the average reaction yield is above70.0%. Finally, with cuprous chloride as the catalyst, two series of4’-1,2,3-triazole coumarins which are composed of10new compounds were synthesized by means of "Click" chemical reactions between alkynes and4-azidomethyl-naphthol coumarin in acetone solvent. This "Click" reaction showed many advantages such as high regioselectivity, mild reaction conditions, less by-products, and high reaction yield.At the same time, we also explored the synthesis of other new coumarin derivatives by means of nucleophilic substitution reaction between4-chloromethyl-naphthol coumarin and N-phenylpiperazine in DMF at80℃. The target products were expected to exhibit good biological activity especially anti-bacterial activity. The structures of all new coumarin derivatives were characterized and eventually confirmed by1H NMR,13C NMR, FRIR, and MS. |
