In Chinese vocabulary, the terms cis-3-Hexenol, Geraniol, and beta-Eudesmol all contain the characters for ‘leaf alcohol’ (叶醇). Without delving deeper into understanding them, many people may assume that they are related compounds. These natural compounds come from various plants and have unique chemical structures, physical and chemical properties, and practical applications. This article introduces an overview in three sections based on three characteristics: cis-3-Hexenol, Geraniol, and beta-Eudesmol.

cis-3-Hexenol

Cis-3-Hexenol, also known as ‘leaf alcohol,’ is an unsaturated alcohol. Japanese agricultural chemist Sankichi Takei (たけい さんきち) [1] discovered this class of substances in tea leaves from the Uji tea-producing region of Kyoto in the 1930s, and referred to it as ‘青 葉 ア ル コ ー ル’ (green leaf alcohol). When leaves or grass are cut or damaged, they emit a pungent odor reminiscent of freshly cut grass. This odor, similar to green onion, is known as ‘green leaf volatiles (GLVs).’ This occurs as lipoxygenase (LOX) starts to break down plant cell membranes, producing polyunsaturated fatty acids like linoleic and linolenic acids. Lipoxygenase catalyzes the dioxygenation of lipids containing cis,cis-1,4-pentadiene into cell signaling agents. The substances formed in this process are exposed to air, forming cis-3-hexenal, which is rapidly further decomposed into cis-3-hexenol (leaf alcohol) and (E)-2-hexenal (leaf aldehyde). These oxidized hydrocarbons are responsible for the green odor [2].

The green odor released by cis-3-hexenol can also be attributed to herbivore-induced plant volatiles (HIPVs) triggered by herbivores or insects. Volatiles act as signaling molecules that regulate the communication between nearby cells (paracrine signaling) and distant cells (endocrine signaling). Therefore, compounds of cis-3-hexenol from different plants may attract or repel different insects accordingly. For example, cis-3-hexenol can attract male scarab beetles and beetles, while repelling weevils.

Apart from extracting cis-3-Hexenol from plant volatile oils, it can also be industrially prepared using butadiene and formaldehyde as raw materials to produce 2-Methyl-5,6-dihydropyran, which is then ring-opened under lithium catalysis [4]. Takasago from Japan is the main producer using this preparation method. Besides Takasago, ZEON from Japan and NHU (Xinhecheng) from China are also important producers of cis-3-Hexenol. Known for its natural floral and green aroma characteristics, cis-3-Hexenol is used as a fragrance in perfumery, particularly as a top note in lily-of-the-valley and clove scents. In food flavor formulations, it is applied in mint and fruit flavor recipes.

cis-3-hexenyl acetate

Cis-3-Hexenyl Acetate, also known as z3HAC, is a colorless to pale yellow liquid with a strong green aroma. Industrially, it can be made by reacting cis-3-hexen-1-ol (cis-3-Hexenol) with acetic acid (or acetic anhydride) through esterification or transesterification reactions. In the 1969 publication “Perfume and Flavor Chemicals,” S.Arctander considered synthetic derived compounds of hexenol, like cis-3-hexenal-di-cis-3-hexenyl acetal, had low purity and unstable properties, and were not practically useful in the fragrance and flavor industry. Shortly after, Hiroshi Horino and Shin-Ichi Hirakawa from ZEON in Japan found that highly purified synthetic hexenol compounds had a strong aroma and enough stability, making them suitable for use in the fragrance and flavor industry or pharmaceuticals (Patent EP0738700A1).

Cis-3-Hexenyl Acetate is now an FDA and EU-approved food additive, used for flavoring in banana, candy, floral, and green flavors. It is also commonly employed in fragrance formulations for personal care products. Additionally, it finds wide application in air fresheners, scented candles, bathroom surface cleaners, and car interior cleaners.

Cis-3-Hexenyl Acetate is also an effective semiochemical, capable of stimulating plant defense, attracting herbivores and their predators, and participating in inter-plant communication and defense initiation [5]. Frost suggests that after gypsy moth (Lymantria dispar) consumes coniferous or deciduous leaves, the leaves exposed to z3HAC show higher concentrations of jasmonic acid and linolenic acid. This also stimulates the release of terpenoid volatiles [6]. Woody plants use z3HAC as a signal to start their defense mechanism before facing herbivory. The compound cis-3-Hexenyl Acetate in maize volatiles attracts the oviposition behavior of Spodoptera frugiperda [7]. Through experiments, Ya-Lan Sun demonstrated that using only cis-3-Hexenyl Acetate can enhance the parasitic efficiency of Cotesia chlorideae as a biological control agent, inhibiting the growth of agricultural pests like Helicoverpa armigera [8].

cis-3-Hexenyl Benzoate

Cis-3-Hexenyl benzoate is a colorless to pale yellow, slightly thick oily liquid, with a delicate and long-lasting scent of grass, herbs, and woody notes. It naturally occurs in jasmine, gardenia, and tea, and serves as a major fragrance compound in jasmine tea aroma [9, 10]. It can be synthesized industrially by esterifying benzoic acid with cis-3-hexen-1-ol (cis-3-Hexenol) or by transesterifying methyl benzoate with cis-3-hexen-1-ol. It is an FDA and EU-approved food additive. In fragrance applications, it is often used in combination with cis-3-Hexenyl Acetate and cis-3-Hexenol. This is highly suitable for use in products like soaps, hand washes, shampoos, shower gels, and conditioners.

There is limited documentation about the use of cis-3-Hexenyl Benzoate in plant protection applications. SONG PINGPING found that the content of cis-3-Hexenyl Benzoate in the female flower buds of snake gourd (Trichosanthes anguina L.) is relatively high. It specifically binds to odorant-binding proteins in the brown marmorated stink bug (Halyomorpha halys) and the green stink bug (Plautia stali), similar to the alarm pheromones of these pests, and has repellent properties [11]. This helps female flowers avoid pests, protecting pollination and the development of female flowers.

cis-3-Hexenyl Salicylate

Cis-3-Hexenyl Salicylate is a colorless, transparent liquid with a fresh fragrance. It can be synthesized by combining salicylic acid and cis-3-hexen-1-ol (cis-3-Hexenol) in an esterification reaction, or by using methyl salicylate and cis-3-hexen-1-ol in a transesterification reaction. It is an EU-approved food additive. In terms of fragrance, it has the floral and seaside scent of lily-of-the-valley, giving a fresh aroma. Compared to hexyl salicylate, it has a stronger scent of green notes rather than floral, and it also provides an elegant alternative to amyl salicylate.

This compound is suitable for use in antiperspirants, bath products, laundry detergents, cleansers, conditioners, fabric care products, and other items. However, its performance in shampoo and hand wash formulations is mediocre. cis-3-Hexenyl Salicylate is a salicylate commonly used in perfume formulations. For example, it is used in Cacharel’s Anais Anais L’Original EDT.

cis-3-hexenyl butyrate

Cis-3-hexenyl butyrate is a colorless to pale yellow oily liquid, accompanied by fruity and green notes. It is the main ester green leaf volatile (GLV) of rocket salad leaves (Eruca sativa) [12] and is also an important aromatic compound in white tea [13]. It naturally occurs in mangoes and passion fruits. Cis-3-hexenyl butyrate is primarily produced by esterification of cis-3-Hexenol and butyric acid, or by transesterification of cis-3-Hexenol and methyl butyrate. It is an FDA and EU-approved edible fragrance. Cis-3-hexenyl butyrate has a distinct apple aroma, accompanied by a scent reminiscent of brandy. In fragrance formulations, it is suitable for use in perfumes, hand washes, shampoos, conditioners, shower gels, detergents, and other formulations.

In pheromone applications, cis-3-hexenyl butyrate can attract wasps (Vespula spp.) [14].

Geraniol

Geraniol is a naturally occurring acyclic-isoprenoid monoterpene alcohol. It is found in over 250 plants such as geraniums, ruta app, Litsea cubeba, lemongrass, and roses [15]. Nerolidol is an isomer of geraniol, both having similar boiling points, with a difference of ±2°C under normal pressure. The similar boiling points of geraniol and other plant volatile oils often make it challenging to extract them naturally. For example, the boiling point of geraniol and citronellol only differs by about 5°C under normal pressure. Currently, natural extraction is the main method for preparing geraniol.

Geraniol can also be prepared through industrial synthesis. Synthesizing geraniol can be achieved by using Myrcene [16] or Linalool [17] as starting materials. The main production method in factories currently involves using Citral as the starting material [18].

Geraniol has a sweet, floral-rose, fruity-berry, and waxy citrus fragrance. Especially when extracted from roses and geraniums, it is commonly used in premium fragrance formulations. Arctander describes it as “usually used as a sweet floral ingredient.” It forms the basis of artificial ylang-ylang, peony, sweet pea, and other fragrances.” In the book “Diary of a Nose,” Jean Claude Elena comments on geraniol: “Geraniol, when combined with β-ionone, frambinone, and fructone, can produce scent characteristics reminiscent of raspberry.”

When used as a fragrance, geraniol has broad compatibility and can be applied in various everyday chemical products like perfumes, deodorants, lipsticks, lotions, soaps, shower gels, shampoos, cleansers, and detergents. It is also used as a sweetener in food flavorings.

Another major application of geraniol is in the medical field. It has medicinal value, including antibacterial, cardiovascular protection, anticancer, and neuroprotective properties [19]. Researchers believe that this is related to the metabolism of geraniol [20]. For example, geraniol can inhibit the activity of CYP2B6 in the metabolism of xenobiotics in the liver, thus being used for chemoprevention against the activation of carcinogens. Geraniol also has non-polar characteristics, which can disrupt the lipid structure of microbial cell membranes and enhance the permeability of other compounds such as antibiotics [21].

beta-Eudesmol

Beta-eudesmol is a sesquiterpene cyclic compound, appearing as a white to light brown powder or chunks. It is naturally found in plants such as hops, ginger, rhizomes of Atractylodes lancea, and Eucalyptus globulus. In hops, beta-eudesmol contributes to flavor and bitterness [22]. It is also a major active component in Atractylodes lancea [23], hence there is much exploration of its potential medicinal value. Atractylodes lancea is a herbal medicine in traditional medicine, mainly used for ailments related to the spleen and stomach, abdominal distension, rheumatism, colds with wind-chill, and night blindness. Studies suggest that this is due to the accumulation or release of volatile sesquiterpenes in the rhizomes and roots [24]. Beta-eudesmol is believed to have therapeutic effects on epilepsy, dementia, and cardiovascular diseases [25].

Beta-eudesmol can be naturally extracted from Atractylodes lancea and Magnolia officinalis, but the yield is low. To increase the production of beta-eudesmol, synthetic biology has emerged as a new technology trend. Research currently suggests converting mevalonate into terpene precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are then added to Escherichia coli. Metabolic engineering of E.coli after transformation has resulted in the production of sesquiterpenes similar to those observed in in vitro enzyme-catalyzed reactions. It has been confirmed that relatively high levels of beta-eudesmol can be feasibly produced from inexpensive carbon sources (mevalonic acid) [25, 26].

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Reference

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