3-O-乙酰基熊果酸3-乙酰基-2-[(未)取代苯基]-2,3-二氢-1,3, -噁二唑-5-甲酯的合成及其抗炎活性研究

熊果酸与氯乙酸乙酯反应制得熊果酸乙氧甲酰基甲酯(2), 2与水合肼反应得到熊果酸甲酰肼甲酯(3), 3与羰基化合物反应得到一系列酰腙4a～4g, 再将4a～4g与乙酸酐作用, 环合得到3-O-乙酰基熊果酸3-乙酰基-2-[(未)取代苯基]-2,3-二氢-1,3,4-噁二唑-5-甲酯(5a～5g). 15个新化合物均未见文献报道, 其结构经¹H NMR, IR, MS加以确证, 并进行了药理结果筛选. 结果表明, 部分化合物具有良好的抗炎活性. 其中, 化合物5a (40 mg•kg^－1), 5d (40 mg•kg^－1), 5g (40 mg•kg^－1)与熊果酸相比, 具有更强的疗效.

Synthesis and Anti-inflammatory Activity of 3-Acetyl-2-[(un)substituted phenyl]-2,3-dihydro-1,3,4-oxadiazol-5-methyl 3-O-Acetylursolate

Ethoxycarbonylmethyl ursolate obtained by a reaction of ursolic acid with ClCH₂COOC₂H₅ reacted with hydrazine hydrate to give hydrazi-nocarbonylmethyl ursolate (3). Reaction of the hydrazide 3 with keto compounds give the corresponding hydrazones 4a～4g, which could be readily convered to 3-acetyl-2-[(un)substituted phenyl]-2,3-dihydro-1,3,4-oxadiazol-5-methyl 3-O-acetylursolate (5a～5g) in good yields by treatment with Ac₂O. The structures of new products were characterized by ¹H NMR, IR and MS spectra. By the preliminary bio-assay test some of such compounds show good anti-inflammatory activity. For example, compounds 5a (40 mg•kg^－1), 5d (40 mg•kg^－1) and 5g (40 mg•kg^－1) were better than the parent ursolic acid.