Synthesis Of N - Substituted Caramine Derivatives And Their Anticancer Activity

Coumalic acid contains a 2H-pyran-2-one unit.Many compounds that contain2H-pyran-2-one units have very good biological activity,including:anti-tumor effect,antibacterial action,anti-neurotoxic effect,anti-phytotoxicity effect and the inhibition effects on the HIV protease or acetylcholine esterase.Meanwhile,such compounds could be used for the treatment of Alzheimer’s disease and high cholesterol symptom.SK-F12 is a kind of alkaloids that was extracted from the ocean by SK Chemical Corporation of Korea.Its structure contains a 2H-pyran-2-one unit,the 5 position of which was connected to the alkaloid by single bond.MTT reduction assay was performed to evaluate its anti-tumor activity.Cisplatin was used as positive control and its 50%inhibitory concentration (IC₅₀)value on human lung cancer cells（A549）was 1.56μg / ml,while that of SK-F12 was 0.0014μg / mL.The results showed that SK-F12 had a very good anti-tumoractivity. The further study showed that the 2H-pyran-2-one ring was responsible for its bioactivity.Based on the good anti-tumor activity of SK-F12,we used SK-F12 as lead compound, designed and synthesized 21 N-substitued coumalic amide derivatives,all of which were novel and have not been reported before.The structures of all the compounds have been confirmed by ¹H-NMR and MS spectrometry.