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. 2022 Aug 10;27(16):5082.
doi: 10.3390/molecules27165082.

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

Lidia Lungu  1 , Caleria Cucicova  1 , Svetlana Blaja  1 , Alexandru Ciocarlan  1 , Ion Dragalin  1 , Alic Barba  1 , Nicoleta Vornicu  2 , Elisabeta-Irina Geana  3 , Ionel I Mangalagiu  4 , Aculina Aricu  1
Affiliations

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

Lidia Lungu et al. Molecules. .

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.

Keywords: 1,3-benzothiazole; antifungal and antibacterial activities; homodrimane sesquiterpenoids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Synthesis of 2-homodrimenyl-1,3-benzothiazoles 4, 6, 8, and 9 from carboxylic acids 3, 5, 7 and 2-aminothiophenol.
Figure 1
Figure 1
Selected COSY and HMBC correlations for compound 8.
Scheme 2
Scheme 2
A plausible reaction pathway of formation of compound 8.
Scheme 3
Scheme 3
Synthesis of N-substituted 2-amino-1,3-aminobenzothiazoles 15, 17, 19, and 22 from carboxylic acids 3, 5, 7, 20 and 2-aminobenzothiazole.
Scheme 4
Scheme 4
Synthesis of unexpected compounds 25 and 27.
Figure 2
Figure 2
Selected COSY, HMBC, and NOESY correlations for compound 25.
Figure 3
Figure 3
Selected COSY, HMBC, NOESY, and HMBC correlations for compound 27.
Scheme 5
Scheme 5
Plausible reaction pathway for formation of compound 25.
Scheme 6
Scheme 6
Plausible reaction pathway for formation of compound 27.
See this image and copyright information in PMC

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