An Efficient Directly Conversion of the Ethyl p-Methoxycinnamate into N,N-dimethyl-p-Methoxycinnamamide and study the structure-activity relationship on anti-inflammatory activity

Ismiarni Komala,Ahmad Thantow,Supandi Supandi,Andrianopsyah Mas Jaya Putra

doi:10.22146/ijp.812

Abstract

Ethyl p-methoxycinnamate (EPMC) (1) is a major natural ester found in the rhizome of Kaempferia galanga and has been reported to have anti-inflammatory activity. Some of the structural modification of this compound has been carried out in order to study the structure-activity relationship on its anti-inflammatory activity. In the present study, we report a new, simple and efficient procedure in the conversion of the ethyl p-methoxycinnamate into N,N-dimethyl-p-methoxycinnamamide (5) and then study the structure-activity relationship on its anti-inflammatory activity. The reaction was carried out through a microwave-assisted direct amidation between (EPMC) (1) with dimethylformamide (DMF) in the basic condition. The mixture was irradiated by using unmodified microwave-oven at 300 W for 1 minute to obtain compound (5) in 88.8% yields. The extensive analysis of the GCMS and NMR data supported that the product of synthesis is N,N-dimethyl-p-methoxycinnamamide (5). Evaluation of the anti-inflammatory activity of compound 5 by using anti-denaturation of heat bovine serum albumin (BSA) assay indicated that N,N-dimethyl-p-methoxycinnamamide (5) still have anti-denaturation activity. Compound 5 has an amide functional group which is more slowly hydrolyzed if compared to 1. Hence, the reaction has successfully produced a more stable compound which still has anti-inflammatory activity

Highlights

Ethyl p-methoxycinnamate (EPMC) (1) is an ester anti-inflammatory compound that is isolated from the rhizome of Kaempferia galanga (Komala, et al, 2018; Komala et al, 2017)
Our previous research suggested that ethyl ester of the EPMC (1) is responsible for its anti-inflammatory properties
In order to find an optimal condition of reaction, initially, EPMC (1 mmol) and DMF (2mL) were reacted in a variety amount of NaOH in 2mL ethanol

Summary

Introduction

Ethyl p-methoxycinnamate (EPMC) (1) is an ester anti-inflammatory compound that is isolated from the rhizome of Kaempferia galanga (Komala, et al, 2018; Komala et al, 2017). In order to circumvent carboxylate-ammonium salts formation in this reaction, the reaction needs to be conducted at very harsh conditions (>100 C).it is necessary to initiate the activate carboxylic acids by using coupling reagent prior to treatment with amines (Figueiredo, et al, 2016; Pattabiraman and Bode, 2011) In recent research, it has been developed the catalytic protocol in performing direct amidation of carboxylic acids with amines, in which boronic acid. Ismiarni Komala derivatives are found as a prominent catalyst used (Pattabiraman and Bode, 2011; Sabatini, et al, 2017) Another method that is currently being considered in order to form amide bonds is a direct amidation of the ester by using a variation of amines. The product of the reaction was evaluated for its antiinflammatory activity and further analyzed for its structure-activity relationship on the antiinflammatory activity

Methods

Results

Conclusion