SYNTHESIS AND PROPERTIES OF NEW N-ACYL DERIVATIVES OF ANTHRANILIC ACID

Abstract

A series of N-acyl derivatives of anthranil (or o -aminobenzoic acid) was first synthesized, namely 2-(4-octylbenzamido)benzoic acid, 2-(4-(heptyloxy)- benzamido)benzoic acid, 2-(4-(heptylsulfanyl)benz-amido)benzoic acid. 2-(4-octylbenzamido)benzoic acid was synthesized in five stages of octylbenzene, by acylating chloride acid using a Friedie-Crafts reaction. 2-(4-(heptyloxy)benzamido)benzoic acid was prepared from the methyl ester of p-hydroxybenzoic acid which, at the first stage, was activated with 1-bromoheptane in acetonitrile with potassium carbonate and catalytic amount of sodium iodide at heating. After that, hydrolysis of the ester group by hydroxide in the methanol–water system was performed. Synthesis of 2-(4-(heptylsulfanyl)benzamido)benzoic acid was carried out from p-sulfanylbenzoic acid, which was activated with 1-bromoheptane, in a system of ethanol–water with sodium hydroxide. Chlorinated hydrides of acids were obtained by reaction of acids with chlorinated thionyl in benzene. Acylation of the tret-butyl ester of anthranilic acid with formed chlorohydrides was carried out in pyridine upon heating and in dichloromethane with triethylamine (as the base), and dimethylaminopyridine (catalyst).At the last stage of the synthesis of all derivatives, the hydrolysis of tret-butyl esters with trifluoroacetic acid in dichloromethane to the formation of terminal compounds took place.The composition and structure of the synthesized compounds were determined using NMR 1H, infrared spectroscopy. The shape and position of the bands in the IR absorption spectra of the synthesized anthranilic acid derivatives are shifted and splited in comparison with the parent acid due to the presence of a secondary amino group, an additional aromatic moiety, and a different nature of the substitutes in the para-position to the amino group. For all synthesized derivatives, the sensitivity of various morphological forms Candida albicans was determined. The influence of the test substances on the cells of the yeast fungus was determined for 24–48 hours using Saburo and Spider nutrient media with the  addition of mannitol. Compared with the already known influence of anthranilic acid on Candida albicans cells grown in Saburo nutrient medium for 24 hours, the compounds studied were more effective at all stages of cultivation. It has been shown that the synthetic derivatives studied are more active with respect to the cells in the biofilm composition, which consists of the yeast-like form of Candida albicans, than those cells that form a hyphal type biofilm. The yeast-like form of the Candida albicans cell is susceptible to synthetic derivatives. It is shown that the level of sensitivity of compounds 1-3 is higher in 4-6 times compared with anthranilic acid. Glyphs have been found to be more susceptible to the effects of the compounds studied than Е yeast cells of Candida albicans