Natural crystalline fibers of (E)-(R)-4-thujanol: green kilogram production from a selected wild thyme. X-ray and NMR characterization of a spiral structure

(E)-(R)-4-Thujanol present in thyme essential oils is an important aromatic ingredient for food, cosmetic and pharmaceutical applications. Until now, its extraction was challenging due to its low content in classical aromatic plants such as thyme or marjoram. Although this molecule is synthetically available, there is no production on an industrial scale because of very time-consuming and expensive chemical processes. We report here for the first time a new eco-responsible method to produce (E)-(R)-4-thujanol crystals on a kilogram scale. This new milestone is based on 2 fundamental research gaps: i) the selection of a wild thyme (Thymus vulgaris) for its high content of (E)-(R)-4-thujanol and its careful harvesting in the hills of French Provence and ii) a steam distillation producing an organic aromatic oil which aggregates spontaneously due to a favorable amphipathic partition at the air-water interface. Gas chromatography revealed a composition made of (E)-(R)-4-thujanol (76%), thymol (5%), β-myrcene (2,8%) and other minor monoterpenes. The white aggregate submitted to a cycle of sublimation/crystallization, led to accumulating translucent fibers made of (E)-(R)-4-thujanol (98%). X-ray diffraction unambiguously demonstrated that crystals of (E)-(R)-4-thujanol form a trimer (monoclinic asymmetric (C2)) unit composed of three independent (E)-(R)-4-thujanol molecules. The trimer is further organized into a chiral P-type supramolecular helix of trimers through a network of intermolecular hydrogen bonds. This study is based on the cheap, easy and eco-responsible kilogram production of (E)-(R)-4-thujanol crystals may open up new opportunities for the flavor, fragrance and pharmaceutical industries. Fibers of (E)-(R)-4-thujanol may also have applications as bio-active fibrous assemblies.