Herein we report a feasible study concerning the synthesis and the in vitro antimicrobial activity of some new homodrimane sesquiterpenoids with a benzimidazole unit. Based on some homodrimane carboxylic acids, on their acyl chlorides and intermediate monoamides, a series of seven N-homodrimenoyl-2-amino-1,3-benzimidazoles and 2-homodrimenyl-1,3-benzimidazoles was synthesized. The syntheses involved the decarboxylative cyclization and condensation of the said acids or acyl chlorides with o-phenylendiamine and 2-aminobenzimidazole, as well as the p-TsOH-mediated cyclodehydration of the said monoacylamides. The structures of the synthesized compounds have been fully confirmed, including by the X-ray diffraction. 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). Compounds 7 and 20 showed higher antifungal (MIC = 0.064 and 0.05 μg/mL) and antibacterial (MIC = 0.05 and 0.032 μg/mL) activities compared to those of the standards: caspofungin (MIC = 0.32 μg/mL) and kanamycin (MIC = 2.0 μg/mL), and compounds 4, 10, 14, and 19 had moderate activities.

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.