Compound 4-hydroxyphenylglyoxal hydrate was chosen as starting material, which can react with N-methoxylamine hydrochloride in one step of oximation reaction, affording phenolic natural product buxifoximes A in yield of 79%. Meanwhile, we also synthesized compound 2, a natural analogue of Buxifoximes A, according to a known procedure. Furthermore, the inhibitory effect of compound and compound 2 on cancer cell proliferation was evaluated and found to possess potent inhibitory activity against MV4-11. Meanwhile, preliminary structure–activity relationships for these two compounds are discussed.