Synthesis of Homodrimane Sesquiterpenoids Bearing 1,3-Benzothiazole Unit and Their Antimicrobial Activity Evaluation

Abstract

Based on some homodrimane carboxylic acids and their acyl chlorides, a series of fourteen 2-homodrimenyl-1,3-benzothiazoles, N-homodrimenoyl-2-amino-1,3-benzothiazoles, 4′-methyl-homodrimenoyl anilides and 4′-methyl-homodrimenthioyl anilides were synthesized and their biological activities were evaluated on five species of fungi (Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, and Alternaria alternata) and two strains of bacteria (Bacillus sp. and Pseudomonas aeruginosa). The synthesis involved the decarboxylative cyclization, condensation and thionation of the said acids, anhydrides or their derivatives with 2-aminothiophenol, 2-aminobenzothiazole, p-toluidine and Lawesson’s reagent. As a result, together with the desired compounds, some unexpected products 8, 25, and 27 were obtained, and the structures and mechanisms for their formation have been proposed. Compounds 4, 9, and 25 showed higher antifungal and antibacterial activity compared to the standards caspofungin (MIC = 1.5 μg/mL) and kanamycin (MIC = 3.0 μg/mL), while compound 8 had comparable activities. In addition, compounds 6, 17, and 27 showed selective antifungal activity at MIC = 2.0, 0.25, and 1.0 μg/mL, respectively.