Synthesis and Antimicrobial Activity Evaluation of Homodrimane Sesquiterpenoids with a Benzimidazole Unit.

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.

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

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.

Synthesis, structural elucidation and biological evaluations of new guanidine-containing terpenoids as anticancer agents.

Using sclareol and sclareolide as starting materials, the guanidine derivatives of 12-amino-11-dihomodrimane-8α-ol and 13-amino-14,15-bis-dinorlabd-8(9)-ene were synthesized by the reaction of the corresponding amines with sodium hydrogencyanamide in ethanol - water solution. Monoacyl- and diacylguanidines were prepared from activated with N,N-carbonyldiimidazole Δ8,9-bicyclohomofarnesenoic acid by the reaction with guanidine. Their structures were confirmed by the 1H and 13C NMR, IR spectral and elemental analysis data. The compounds 12, 13 and 15 were screened for their antiproliferative and cytotoxicity activities against Colo 205, Colo 320 and MRC 5 human lung fibroblasts with respect to standard drug, Cisplatin. The compounds 12 and 15 exhibits excellent results than positive control. Hence these two compounds may be act as drug lead molecules in cancer chemotherapy.

Synthesis of (-)-albrassitriol and (-)-6-epi-albrassitriol from (+)-larixol.

A novel synthesis of natural drimanic compounds, (-)-albrassitriol (2) and (-)-6-epi-albrassitriol (3), has been carried out starting from an easily available labdane diterpenoid, (+)-larixol (1). In a two-step procedure, (+)-larixol (1) was converted into 14,15-bisnorlab-7-ene-6,13-dione (9), which was then submitted to a Norrish type II photochemical degradation yielding drim-7,9(11)-diene-6-one (10), whose treatment with OsO4 led selectively to the formation of drim-7-ene-9α,11-diol-6-one (12). The same compound was obtained by selective epoxidation of the C(9)-C(11) double bond in drim-7,9(11)-diene-6-one (10) with monoperphtalic acid. Treatment of the resulting mixture of α- and ß-epoxides (13 and 14) with HClO4 yielded drim-7-ene-9α,11-diol-6-one (12). Reduction of the C6-carbonyl group in drim-7-ene-9α,11-diol-6-one (12) with LiAlH4 afforded (-)-albrassitriol (2) and (-)-6-epi-albrassitriol (3), 12.4% and 13.6% overall yields, respectively.