CHEMISTRY JOURNAL OF MOLDOVA. General, Industrial and Ecological Chemistry. 2023, 18(1), 86-91 ISSN (p) 1857-1727 ISSN (e) 2345-1688 http://cjm.ichem.md http://doi.org/10.19261/cjm.2022.1026 © Chemistry Journal of Moldova CC-BY 4.0 License SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF TETRANORLABDANE COMPOUNDS BEARING 1,3,4-THIADIAZOLE UNITS Svetlana Blaja a , Lidia Lungu a* , Alexandru Ciocarlan a , Nicoleta Vornicu b , Aculina Aricu a a Institute of Chemistry, 3, Academiei str., Chisinau MD-2028, Republic of Moldova b Metropolitan Center of Research TABOR, 9, Closca str., Iasi RO-700066, Romania * e-mail: lidia.lungu@ichem.md Abstract. Synthesis of novel tetranorlabdane compounds bearing 1,3,4-thiadiazole units and intermediary tetranorlabdane compounds with thiosemicarbazone fragment has been reported. The structures of the new synthesized compounds were confirmed using IR and 1 H, 13 C, and 15 N NMR spectroscopy. The in vitro antifungal and antibacterial activities of the mentioned compounds have been evaluated. Results of this study have shown that the 1,3,4-thiadiazole-2-imine has excellent activity against tested strains of fungi and species of bacteria at minimum inhibitory concentration values of 0.125 and 2.5 µg/mL, respectively. Keywords: (+)-sclareolide, tetranorlabdane compound, 1,3,4-thiadiazole, thiosemicarbazone, antimicrobial activity. Received: 18 October 2022/ Revised final: 18 January 2023/ Accepted: 23 January 2023 Introduction From the diversity of terpenic compounds, labdane diterpenoids, which contain the bicyclic trans-decalin system, are of particular interest, many of them being natural or synthetic products of practical importance [1]. The labdane type diterpenes have been described to have broad spectrum of biological activities [2-4]. Compounds that contain heterocyclic fragments in their molecules often exhibit pronounced biological activities. Thiadiazoles are a very important class of heterocyclic compounds. During recent years remarkable progress has been made in the development of new thiadiazole compounds, many of which possess interesting biological activities such as anticancer, antituberculous, antimicrobial, anti‐inflammatory, analgesic and anticonvulsant, etc. [5,6]. A wide variety of methods and reagents which lead to 1,3,4-thiadiazole are known. One of the most used methods of their synthesis employs the cyclocondensation of acid hydrazides with triethyl orthoalkanates [7], isothiocyanates or dithiocarbamates [8]. Frequently, the synthesis of mentioned heterocycles involves the formation of intermediary thiosemicarbazones by the interaction of the thiosemicarbazide and acids [9] or aldehydes [10], followed by their subsequent heterocyclization. The synthesis of novel hybrid compounds containing both terpenic and heterocyclic units is a promising direction of research in organic chemistry. Series of compounds containing both terpene and diazine [11,12], azaheterocyclic [13,14], 1,2,4-triazole and carbazole [15,16], hydrazinecarbothioamide and 1,2,4-triazole [17], thiosemicarbazone and 1,3-thiazole [18], 1,3,4-oxadiazole and 1,3,4-thiadiazole [19] units were reported, many of synthesized compounds exhibit excellent antifungal and/or antibacterial activity. The aim of this study was to synthesize the novel tetranorlabdane compounds bearing 1,3,4-thiadiazole units via some important intermediary tetranorlabdane compounds comprising the thiosemicarbazone fragment. The structures of the synthesized compounds have been fully confirmed by spectral analyses (IR, 1 H, 13 C, and 15 N NMR). Their antifungal and antibacterial activity was tested against several fungi and bacteria taxons. Experimental Generalities The following reagents and solvents were used in the research: thiosemicarbazide, allylthiosemicarbazide, phenylthiosemicarbazide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide 86