Abstract:

Using 3-carene, a major component of turpentine, as the raw material, 3-isopropyl-5-cresol(1) and carvacrol(2) were first synthesized, and then 14 carbamate compounds containing isopropyl cresol structure were further prepared by their reactions with isocyanates(method A) or carbamoyl chlorides(method B). The acetylcholinesterase(AChE) inhibitory activities for all synthetic compounds were studied. The research results showed that the reaction of phenolic compounds with isocyanates was an efficient synthesis process for the preparation of carbamates. The larger N-substituent structure in the isocyanate, the easier reaction occurs, and the molar yield of aryl substitution products could reach more than 90%. In terms of AChE inhibition, the activities of 3-isopropyl-5-cresol derivatives were generally higher than those of carvacrol derivatives. The activities of N-aliphatic substituted products were significantly higher than those of N-aryl substituted products, and the activities of short-chain aliphatic substituted products were higher than those of long-chain aliphatic and cycloaliphatic groups substituted products. The N-methyl substituted product of 3-isopropyl-5-cresol showed the excellent AChE inhibitory activity of 90.5% against Huperzine A and surpassed the positive control Listigmine(89.6%), which was a commercial AChE inhibitor with carbamate. The activity of N, N-dimethyl substituted product of 3-isopropyl-5-cresol was evidently higher than its N-methyl substituted product, whose inhibition efficiency reached 97.9% of Huperzine A. The relationship between the concentration and the inhibition rate showed that 3-isopropyl-5-methylphenyl-N, N-dimethylcarbamate(Ⅰ-2) had a substantially equivalent AChE inhibitory activity to Huperzine A when the concentration was greater than 1.25 mmol/L, indicating that it had the potential to be developed as a therapeutic drug for Alzheimer's disease or insecticide.

Key words: turpentine, 3-carene, carbamate, acetylcholinesterase inhibitor, 3-isopropyl-5-methylphenyl-N, N-dimethylcarbamate