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目的在研究非糖类α-糖苷酶抑制剂的过程中,发现3-(4-苯磺酰氨基)苯甲酰基-2H-1-苯并吡喃-2-酮类化合物具有显著的α-糖苷酶抑制活性。为进一步探讨该类化合物的构效关系,将4-位的苯磺酰氨基替换为甲磺酰氨基和乙酰氨基,合成3-(4-甲磺酰胺基/乙酰基)苯甲酰基-2H-1-苯并吡喃-2-酮类化合物,并评价其α-糖苷酶抑制活性。方法以4-硝基苯甲酸为原料,经氯代、酰化、水解、还原反应制得4-氨基-β-氧代苯丙酸乙酯,与甲磺酰氯/乙酰氯经酰化反应得4-甲磺酰氨基/乙酰氨基-β-氧代苯丙酸乙酯,再与取代水杨醛经Knoev-ernagel缩合,同时环合得到目标化合物。采用酵母α-葡萄糖苷酶对所合成的目标化合物进行α-糖苷酶抑制活性评价。结果合成了22个目标化合物,结构经1H-NMR和IR确证。大部分3-(4-甲磺酰氨基/乙酰氨基)苯甲酰基-2H-1-苯并吡喃-2-酮类化合物未表现出α-糖苷酶抑制活性,只有化合物3-(4-甲磺酰氨基)苯甲酰基-6,8-二叔丁基-2H-1-苯并吡喃-2-酮(10f)表现出良好的α-糖苷酶抑制活性,IC50值为10.16μmol.L-1。结论对于3-苯甲酰基-2H-1-苯并吡喃-2-酮类化合物,其苯甲酰基以4-位甲磺酰氨基/乙酰氨基取代对该类化合物的α-糖苷酶抑制活性不利,该类化合物的构效关系值得进一步研究。
OBJECTIVE In the process of studying non-sugar α-glycosidase inhibitors, 3- (4-phenylsulfonylamino) benzoyl-2H-1-benzopyran-2-ones were found to have significant α- Glycosidase inhibitory activity. To further explore the structure-activity relationship of this class of compounds, 4- (4-methanesulfonamido) was substituted with methanesulfonamido and acetamido to synthesize 3- (4-methanesulfonamido / acetyl) 1-benzopyran-2-ones, and their α-glycosidase inhibitory activity was evaluated. Methods 4-Nitro-benzoic acid was used as starting material to prepare ethyl 4-amino-β-oxobenzene propionate by chlorination, acylation, hydrolysis and reduction. After acylation with methanesulfonyl chloride / 4-methanesulfonamido / acetylamino-β-oxobenzenepropanoic acid ethyl ester, and then replaced with salicylaldehyde Knoev-ernagel condensation, while cyclization to give the target compound. The synthesized target compounds were evaluated for α-glycosidase inhibitory activity using yeast α-glucosidase. Results Twenty-two target compounds were synthesized and their structures were confirmed by 1H-NMR and IR. Most of the 3- (4-methanesulfonamido / acetylamino) benzoyl-2H-1-benzopyran-2-ones showed no a-glucosidase inhibitory activity except that the compound 3- (4- Methanesulfonylamino) benzoyl-6,8-di-tert-butyl-2H-1-benzopyran-2-one (10f) showed a good α-glycosidase inhibitory activity with an IC 50 value of 10.16 μmol. L-1. Conclusions For 3-benzoyl-2H-1-benzopyran-2-ones, the benzoyl group substitutes the 4-position mesylamino / acetylamino group for the α-glucosidase inhibitory activity Adverse, the structure-activity relationship of these compounds deserves further study.