Systematic evaluation of thymol derivatives possessing stereogenic or prostereogenic centers

Thymol (2-isopropyl-5-methylphenol) is an aromatic molecule typically distributed in the genera Thymus and Origanum, which possesses both pharmacological and industrial relevance. This review highlights thymol derivatives with a stereogenic or prostereogenic center, which are distributed in 42 genera of the Asteraceae family whose chemotaxonomy is also outlined. In order to achieve a systematic analysis, which includes a structural examination and accounts for the vegetal sources, the reviewed thymol derivatives were grouped into mono-, di-, and multisubstituted compounds. According to the substitution on the aromatic ring, as well as on the isopropyl residue, and considering the functional groups, an evaluation of the 1H NMR signals, including multiplicities, was carried out. Optical activity data compilation of thymol derivatives revealed that 21 molecules show no optical activity in spite of having a stereogenic center, while two groups of 16 and 15 compounds exhibit, respectively, levorotatory and dextrorotatory optical activity. In addition, two thymol derivatives showed different optical behavior depending on the vegetal source, and only in a single case, the absolute configuration of a thymol derivative is known. Some 10 % of the known functionalized thymol derivatives have been evaluated biologically as antibacterial, anti-inflammatory, antiprotozoal, antioxidant, cytotoxic, piscicidal or allelopathic agents, being the last biological activity the most assayed one.