How is bisabolol obtained?

Bisabolol, also known as levomenol, is a monocyclic sesquiterpene alcohol found in certain essential oils. It is particularly prevalent in wild chamomile and candeia. The bisabolol is a highly utilised active ingredient in cosmetics due to its numerous benefits for the skin, the scalp and hair. It is suitable for all skin types and is particularly well-suited to sensitive, irritated or dry skin.

As anhumectant, bisabolol functions by retaining the water present in the skin and reducing insensible losses, which helps to maintain the skin barrier. Moreover, it possesses antioxidant properties that enable it to protect the skin against oxidative stress. Finally, several studies have highlighted the healing and soothing effects of this ingredient, as well as its anti-inflammatory and antibacterial properties.

The bisabolol found in cosmetic products is often ofplant origin. Here is its extraction process when it comes from the candeia plant. Its method of obtaining from wild chamomile is substantially the same.

1. Harvesting and preparation of candéia bark : Candéia trees, primarily grown in Brazil, reach sufficient maturity for the harvesting of their roots around the age of ten years. These are harvested in a way that preserves the trees and the surrounding ecosystem. The candéia bark is then cleaned and dried to remove moisture. After which, it is reduced to small particles using grinders or mills. This facilitates the subsequent extraction of the desired compounds.

2. Steam Distillation : The branches are placed in a still where steam is introduced. The steam passes through the branches and carries away the volatile compounds, including the essential oil, found in the plant tissues. It is then cooled, which allows the water to condense and separate the essential oil. The less dense candéia oil forms the upper phase.

3. Crystallisation and Purification : In order to extract bisabolol from the essential oil, a crystallisation process is carried out. The solution is cooled to form bisabolol crystals which are then purified through filtration and successive washes, to remove any remaining traces of the essential oil.

4. Drying : once purified, the bisabolol is dried using a desiccator, creating a partial vacuum, to eliminate any residual moisture.

This process of obtaining bisabolol results in an active ingredient pure enough to be subsequently incorporated into cosmetic products and has the advantage of being environmentally friendly. However, it is relatively expensive. The bisabolol used in Typology skincare products is extracted using this method.

It is also possible to obtain bisabolol through laboratory synthesisfollowing several successive chemical reactions.

1. Preparation of Precursors : The precursors used for the synthesis of bisabolol are typically petrochemical compounds. These precursors are purified before they are made to react with each other.

2. Diels-Alder Reaction : The key reaction for the synthesis of bisabolol is the Diels-Alder reaction, which involves the cyclo-addition of a diene, a compound with two double bonds, with an alkene, a molecule having a double bond. This allows for the production of a compound referred to as a bisabolol precursor.

3. Hydrogenation : The cyclic precursor obtained from the Diels-Alder reaction undergoes a hydrogenation step, where double bonds are reduced to single bonds. This leads to the formation of bisabolol alcohol.

4. Purification and Refinement : The synthetic bisabolol obtained is then subjected to stages of purification and refinement to remove impurities and achieve a pure form of bisabolol.

This chemical synthesis typically allows for the acquisition of a more pure form of bisabolol than that obtained through plant extraction. However, it is more polluting.

Still under development, the third method of obtaining bisabolol utilises advanced biotechnologies. It is achieved through bacterial fermentation, meaning that it is bacteria, often of the Escherichia coli type, that produce the bisabolol. Here are the main steps followed:

1. Bacterial strain selection : a strain of bacteria, often E. coli, is selected for its ability to express α-synthase, the gene responsible for the synthesis of bisabolol. This gene can notably be obtained from the German chamomile flower.

2. Construction of the Expression Vector : The α-synthase is inserted into an expression vector, which is then introduced into the cells ofE. coli. This vector allows the bacterial cells to produce the enzymes necessary for the conversion of metabolic precursors into bisabolol.

3. Cell Culture and Fermentation : The E. coli cells containing the expression vector are cultivated in a suitable culture medium. The culture conditions, such as temperature, pH, and medium composition, are optimised to promote the production of bisabolol. Fermentation typically lasts several days.

4. Bisabolol Extraction : once the fermentation process is complete, bacterial cells are harvested and bisabolol is extracted from the culture medium. Various extraction methods can be employed, such as solvent extraction or distillation extraction.

5. Purification : The extracted bisabolol is then subjected to purification stages to remove impurities and obtain a purer form of the compound. Purification may involve techniques such as chromatography or crystallisation.

This method of obtaining bisabolol allows for reducing production costs and is environmentally friendly. However, it requires advanced knowledge in genetic engineering and specialised facilities.

• LEE S.-G. & al. Fermentative production and direct extraction of (-)-α-bisabolol in metabolically engineered Escherichia coli. Microbial cell factories (2016).

• OJHA S. & al. Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol. Nutrients (2022).