Sythesis, Characterization And Biological Activities Of Pinonic Acid Derivatives

Molecular modification of natural resources materials with unique and novel structure to produce bioacitive compounds is an impotant direction of natural product research. There is abundant resource of turpentine in China, the major component of which isα-pinene.α-Pinene has been widely used as raw material for the production of some compounds necessary for national economy due to its abundant availability, low cost and active configuration.Sixty two compounds with six kinds were synthesized from 2-(3-acetyl-2, 2-dimethylcyclobutyl)acetic acid (pinonic acid) which was obtained from the oxidation ofα-pinene. Among them 45 compounds were synthesized for the first time. Their structures were characterized by IR, MS, 1H NMR and X-ray diffraction. The antibacterial, repellent and insecticidal activities of the synthetic derivatives were studies in this paper. The structure activity relationships were also studied. This work might lay a solid foundation for further research of new bioacitive compounds.Pinonic acid was synthesized usingα-pinene as raw material, potassium permanganate as oxidant, ammonium sulfate as pH regulator and water as reaction medium. Then 38 compounds of amides,α,β-unsaturated carbonyl compounds, esters and acylthioureas were synthesized through acylation, aldol condensation, esterification, nucleophilic substitution, nucleophilic addition reactions and so on. Among them 22 compounds were synthesized for the first time. The single crystals of three pinonamides were obtained and their crystal structures were analysed. The cyclobutane fragment of the products was not flat and was flexed as though folded from the dimethylsubstituted C atom to the unsubstituted C atom. The conformation of the cyclobutane represented semi-chair.Thirteen acylthioureas were obtained through acylchlorination, nucleophilic substitution, nucleophilic addition reaction from (2, 2-dimethyl-3-ethylcyclobutyl)acetic acid which was obtained from pinonic acid via Wolff-Kishner reaction. The single crystals of three acylthioureas were obtained and their crystal structures were analysed.Eleven new diacylthioureas were obtained through acylchlorination, nucleophilic substitution, nucleophilic addition reaction from 2, 2-dimethylcyclobutyl-1, 3-diacetic acid (sym-homopinic acid) which was obtained from pinonic acid via Willgerodt reaction.The insecticidal activities of three acylthioureas against Bemisia tabaci were test by medicament spraying method. The insecticidal activities of 37 products with six kinds against Ostrinia furnacalis were tested by artificial diet method. The repellent activities of eight kinds of pinonamides against Musca domestica were tested at the concentration of 100 mg/mL by dipped filter paper mathod. The repellent activities of eight kinds of pinonamides against Monomorium pharaonis were tested at the concentration of 100 mg/mL by dipped seeds method. The repellent activities of eight esters and twelve acylthioureas against Aedes albopictus were tested at the concentration of 100 mg/mL. The antibacterial acitivities of 15 pinonamides and 9α,β-unsaturated carbonyl compounds against Clostridium perfringens, Salmonella typhi, K. peneumoniae, P. aeruginosa, E. coli, Staph. Epidermidis and Staph. aureus were tested by minimum inhibitory concentration method.Methyl ester, ethyl ester and pentyl ester of pinonic acid have higher repellent activities against Aedes albopictus. The repellent time of them are up to 2.5 ~ 3.0 h at the concentration of 200 mg/mL. The acylthioureas obtained from (2, 2-dimethylcyclobutyl)acetic acid have better insecticidal activities against Ostrinia furnacalis. Among these acylthioureas the insecticidal acitivities of 1-[2-(3-ethyl-2, 2-dimethylcyclobutyl)acetyl]-3-o-tolylthiourea (6b), 1-[2-(3-ethyl-2, 2-dimethylcyclobutyl)acetyl]-3-(4-trifluoromethylphenyl)thiourea (6h), 1-[2-(3-ethyl-2, 2-dimethylcyclobutyl)acetyl]-3-(2-chlorophenyl)thiourea (6i), 1-[2-(3-ethyl-2, 2-dimethylcyclobutyl)acetyl]-3-(4-chlorophenyl)thiourea (6j) are better than that of other compounds. So esters and acylthioureas derivatives of pinonic acid have potential for further research to explore new repellants and insecticides.