Abstract：OBJECTIVE To carry out stucture modification and bioactivity evaluation of natural product osthole in order to search for candidate antibacterial compounds. METHODS Using osthole as raw material, the intermediates 1 were synthesized by selenium dioxide oxidation, and the intermediates 2 were synthesized by reduction with sodium borohydride. A series of osthol sulfonic ester derivatives were synthesized by reaction of intermediate 2 with sulfonyl chloride. And the antibacterial activities of the products were evaluated by agar dilution method. RESULTS Sixteen title compounds were synthesized, and their structures were clearly elucidated by NMR and MS. The results showed that osthole derivatives had potential activities against the tested bacteria. The MIC of compound 3p against S.aureu and MRSA were 32, 32 μg·mL-1, respectively. The anti-S.aureu activity was significantly better than osthole, close to that of oxacillin, while the activity of anti-MRSA was much higher than those of osthole and oxacillin. CONCLUSION The sulfonate derivatives of osthole are significantly active against MRSA, which are worthy of further structural optimization and study.
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