Extraction, isolation and synthesis of phytochemical derivatives with potential application as (bio)pesticides

Abstract

Nos últimos anos, óleos essenciais (OEs) e outros componentes vegetais tornaram-se importantes fontes naturais de compostos biológicos ativos e/ou matérias-primas para a obtenção de novos derivados por modificações sintéticas com atividades aprimoradas adequadas para diversas aplicações, inclusive como pesticidas. No presente trabalho, uma série de OEs, contendo anetol, estragol e eugenol, foram obtidos a partir de anis estrelado, erva-doce e cravo-da-índia, respetivamente, por hidrodestilação. Um componente vegetal menos volátil, o ácido ginkgólico C17:1, foi obtido de Ginkgo biloba por extração com Soxhlet. O eugenol isolado foi utilizado como material de partida na preparação de 2-metoxi-4-(oxiran-2-ilmetil)fenol e a abertura do anel epóxido foi realizada usando anilina tendo sido obtido o respetivo β-aminoálcool. Tomando como inspiração o ácido ginkgólico isolado, partindo do ácido 2-aminobenzóico e usando 1-bromododecano, obteve-se o ácido 2-(dodecilamino)benzoico. Além disso, outro composto natural, a 4-hidroxiquinolina, foi usada para obter um derivado O alquilado, a 4-(3-cloropropoxi)quinolina. Considerando a pesquisa de novas alternativas sintéticas aos pesticidas convencionais, partiu-se dos ácidos 4-clorobenzoico ou 2- clorobenzoico e 3-bromoanilina, por reação com cloreto de tionilo e trietilamina, obtiveram-se as benzamidas correspondentes. Além disso, o ácido 2-clorobenzoico reagiu com 9-etil-9H-carbazol-3-amina, pelo mesmo procedimento e foi obtida a 2-cloro-N-(9- etil-9H-carbazol-3-il)benzamida. Todos os compostos foram avaliados quanto à sua potencial atividade biológica contra as linhas de insetos Sf9, Spodoptera frugiperda. Os resultados mostraram que os compostos mais relevantes são o ácido ginkgólico, ácido 2-(dodecilamino)benzoico e a N- (3-bromofenil)-4-clorobenzamida, bioinseticidas/inseticidas semissintéticos muito promissores. Com o ácido 2-(dodecilamino)benzoico foram realizados estudos de nanoencapsulamento em lipossomas pela técnica de injeção etanólica, sendo que a eficiência de encapsulação obtida foi de 99%. Este trabalho insere-se no projeto financiado pela FCT, PTDC/ASP-AGR/30154/2017.

In recent years, essential oils (EOs) and other plant components have become important natural sources of active biological compounds and/or raw materials for obtaining new derivatives by synthetic modifications with enhanced activities suitable for various applications, including as pesticides. In the present work, a series of EOs, containing anethole, estragole and eugenol, were obtained from star anise, fennel and clove, respectively, by hydrodistillation. A less volatile plant component, ginkgolic acid C17:1, was obtained from Ginkgo biloba by Soxhlet extraction. The isolated eugenol was used as starting material in the preparation of 2-methoxy-4-(oxiran-2-ylmethyl)phenol and the opening of the epoxide ring was carried out using aniline and the respective β-amino alcohol was obtained. Taking the isolated ginkgolic acid as inspiration, starting from 2-aminobenzoic acid and using 1- bromododecane, 2-(dodecylamino)benzoic acid was obtained. Furthermore, another natural compound, 4-hydroxyquinoline, was used to obtain an O-alkylated derivative, namely 4-(3-chloropropoxy)quinoline. Also considering the search for new synthetic alternatives to conventional pesticides, 4-chlorobenzoic or 2-chlorobenzoic acids and 3- bromoaniline were used, and by reaction with thionyl chloride and triethylamine, the corresponding benzamides were obtained. Furthermore, 2-chlorobenzoic acid was also reacted with 9-ethyl-9H-carbazol-3-amine, following the same procedure, and 2-chloro N-(9-ethyl-9H-carbazol-3-yl) was obtained. All compounds were evaluated for their potential biological activity against the Sf9 insect cell lines, Spodoptera frugiperda. The results showed that the most relevant compounds are ginkgolic acid, 2-(dodecylamino)benzoic acid and N-(3-bromophenyl)-4- chlorobenzamide, being very promising bioinsecticides/semisynthetic insecticides. With 2-(dodecylamino)benzoic acid, nanoencapsulation studies in liposomes were carried out using the ethanol injection technique, and encapsulation efficiency obtained was 99%. This work is part of the FCT-funded project, PTDC/ASP-AGR/30154/2017.