Efficient synthesis of benzimidazolyl-phenoxyacetic acid O-acetylxylopyranosyl and O-acetylgalactopyranosyl esters and their antiviral activity

Abstract

Six benzimidazolylphenoxyacetic acid O-acetylxylopyranosyl and O-acetylgalactopyranosyl esters were synthesized through esterification reactions at room temperature using 4-dimethylaminopyridine as a catalyst and triethylamine as a deacidification reagent. Their structure was confirmed by IR, 1 H NMR spectra, MS, and elemental analysis. The synthesized compounds are all of β-configuration. The results show that DMAP is an effective catalyst; the yields can reach 63.6%. The above esters showed improved antiviral activity against tobacco mosaic virus. Keywords: O-acetylgalactopyranosyl esters, O-acetylxylopyranosyl esters, benzimidazolylphenoxyacetic acid esters, tobacco mosaic virus, DMAP/Et 3 N.A number of authors have reported the bioactivity of benzimidazole and its derivatives. They are applied widely in medicinal chemistry, agriculture, and also as plant virus inhibitors [1][2][3][4].4-Dimethylaminopyridine (DMAP) is widely used in organic synthesis as a nucleophilic reaction catalyst [5,6]. It can efficiently catalyze esterification reactions, but it has been rarely reported as a catalyst for the synthesis of benzimidazolylphenoxyacetic acid esters. In view of the above, and in connection with our recent work on the search for new phytoantiviral agents [7,8], we selected DMAP as a catalyst and Et 3 N as a deacidification reagent for the preparation of saccharide esters 1-6.The reactions are shown in Scheme 1, and the results are summarized in Table 1. We found that the reactions in the presence of DMAP/Et 3 N proceeded quickly and smoothly at room temperature under mild conditions and with a substantially increased yield (up to 63.6%), and decrease in reaction time compared with the phase-transfer catalyst (Bu 4 NBr) method. This method is simple; the amount of catalyst DMAP is small. Optimum reaction conditions were as follows: 1.5-2.5 h at 20-25°C with equimolar ratio of reagents (1 ml of Et 3 N and 0.3 mmol of DMAP for 5.25 mmol of acid).The antiviral activity of benzimidazolylphenoxyacetic acid esters (43-58%) against tobacco mosaic virus (TMV) is higher than that of the parent acids (about 30% [8]), xylopyranosyl derivatives being more active than galactopyranosyl analogues (Table 1).As far as we know, this is the first example of benzimidazolylphenoxyacetic acid saccharide esters synthesized using the DMAP/Et 3 N method. We propose (Scheme 2) that DMAP first reacted with O-acetylglycosyl bromide, quickly forming an unstable intermediate (DMAP salt), with increased __________________________________________________________________________________________