Promising Norlabdane-Heterocyclic Hybrids: Synthesis, Structural Characterization and Antimicrobial Activity Evaluation

Abstract

The terpeno-heterocyclic molecular hybrids are a new and promising class of modern organic and medicinal chemistry, because their molecules exhibit high and selective biological activity, natural origins, and good biocompatibility, and, usually, they are less toxic. The reported norlabdane-heterocyclic hybrids were synthesized by classical and new, original, and environmentally friendly methods, which include coupling reactions of norlabdane derivatives (such as carboxylic acids, acyl chlorides, or bromides) with individual heterocyclic compounds, as well as heterocyclization reactions of certain norlabdane intermediates like hydrazides, thiosemicarbazones, or hydrazinecarbothioamides. The aforementioned norlabdanes were derived from (+)-sclareolide 2, which is readily obtained from (−)-sclareol 1, a labdane-type diterpenoid extracted from the waste biomass of Clary sage (Salvia sclarea L.) that remains after essential oil extraction. All synthesized compounds were tested against various fungal strains and bacterial species, with many exhibiting significant antifungal and antibacterial activity. These findings support the potential application of the synthesized compounds in the treatment of diseases caused by fungi and bacteria. Additionally, the use of plant-based waste materials as starting resources highlights the economic and ecological value of this approach. This review summarizes experimental data on the synthesis and biological activity of norlabdane: diazine, 1,2,4-triazole and carbazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,3-thiazole, 1,3-benzothiazole and 1,3-benzimidazole hybrids performed by our research group covering the period from 2013 to the present.