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Borneol
Borneol
Borneol
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Borneol
(+)-Borneol
(+)-Borneol
(-)-Borneol
(-)-Borneol
Names
IUPAC name
rel-(1R,2S,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ol
Other names
1,7,7-Trimethylbicyclo[2.2.1]heptan-2-endo-ol
endo-2-Bornanol, Borneo camphor
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.006.685 Edit this at Wikidata
EC Number
  • 207-352-6
KEGG
UNII
UN number 1312
  • InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m1/s1 checkY
    Key: DTGKSKDOIYIVQL-WEDXCCLWSA-N checkY
  • InChI=1/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m1/s1
    Key: DTGKSKDOIYIVQL-WEDXCCLWBQ
  • O[C@H]1C[C@H]2CC[C@]1(C)C2(C)C
Properties
C10H18O
Molar mass 154.253 g·mol−1
Appearance colorless to white lumps
Odor pungent, camphor-like
Density 1.011 g/cm3 (20 °C)[1]
Melting point 208 °C (406 °F; 481 K)
Boiling point 213 °C (415 °F; 486 K)
slightly soluble (D-form)
Solubility soluble in chloroform, ethanol, acetone, ether, benzene, toluene, decalin, tetralin
−1.26×10−4 cm3/mol
Hazards
GHS labelling:
GHS02: Flammable
Warning
H228
P210, P240, P241, P280, P370+P378
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
2
0
Flash point 65 °C (149 °F; 338 K)
Safety data sheet (SDS) External MSDS
Related compounds
Related compounds
 Bornane (hydrocarbon)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Borneol is a bicyclic organic compound and a terpene derivative. The hydroxyl group in this compound is placed in an endo position. The exo diastereomer is called isoborneol. Being chiral, borneol exists as enantiomers, both of which are found in nature: d-borneol (also written (+)-borneol) and l-borneol (or (−)-borneol).

Reactions

[edit]

Borneol is oxidized to the ketone (camphor).

Occurrence

[edit]

The compound was identified and named camphre de Bornéo, or Borneo camphor in 1842 by the French chemist Charles Frédéric Gerhardt.[2] Borneol can be found in several species of Heterotheca,[3] Artemisia, Rosmarinus officinalis (rosemary),[4] Dryobalanops aromatica, Blumea balsamifera and Kaempferia galanga.[5]

It is one of the chemical compounds found in castoreum. This compound is gathered from the beaver's plant food.[6]

Synthesis

[edit]

Borneol can be synthesized by reduction of camphor by the Meerwein–Ponndorf–Verley reduction (a reversible process). Industrially, a racemic mixture of camphor is used, leading to a racemic mixture of borneol and isoborneol. The chirality can be controlled by changing the chirality of camphor: (+)-camphor gives (−)-isoborneol and (+)-borneol.[7]

Reduction of camphor with sodium borohydride (fast and irreversible) gives instead the diastereomer isoborneol.

Synthesis of the borneol isomer isoborneol via reduction of camphor.

Natural sources

[edit]

Industrially, natural (+)-borneol is produced from Cinnamomum burmanni (one specific chemotype)[8] and Cinnamomum camphora.[9][10]

Natural (-)-borneol occurs in Blumea balsamifera.[10]

Biosynthesis

[edit]

Borneol is synthesized using DMAPP as the starting material. DMAPP is then converted to GPP, which is acted upon by a bornyl diphosphate synthase to yield a bornyl diphosphate. A phosphatase then removes the phosphate groups, yielding borneol.[11]

The chirality of borneol in a plant depends on the preferred chirality of the bornyl diphosphate synthase. Synthases for either chirality have been sequenced.[11][12]

A downstream product is camphor of either chirality, a reaction catalyzed by (+)-borneol dehydrogenase or (−)-borneol dehydrogenase.

Uses

[edit]

Whereas d-borneol was the enantiomer that used to be the most readily available commercially, the more commercially available enantiomer now is l-borneol, which also occurs in nature.

(+)-Borneol from Dipterocarpus spp. is used in traditional Chinese medicine. An early description is found in the Bencao Gangmu.

Borneol is a component of many essential oils[13] and it is a natural insect repellent.[14] It also generates a TRPM8-mediated cooling sensation similar to menthol.[15]

Laevo-borneol is used in perfumery. It has a balsamic odour type with pine, woody and camphoraceous facets.

Dextro-borneol (dexborneol) is used in edaravone/dexborneol, a drug approved in China for stroke. It is approved in intravenous (2021) and sublingual (2025) forms. The intravenous combination was approved on the basis of trials showing it to be superior to edavarone alone.[16][17]

Toxicology

[edit]

Borneol may cause eye, skin, and respiratory irritation; it is harmful if swallowed.[18] Acute exposure may cause headache, nausea, vomiting, dizziness, lightheadedness, and syncope. Exposure to higher levels or over a longer period of time may cause restlessness, difficulty concentrating, irritability, and seizures.[19]

Skin irritation

[edit]

Borneol has been shown to have little to no irritation effect when applied to the human skin at doses used in fine fragrance formulation.[20] Skin exposure can lead to sensitization and a future allergic reaction even to small quantities.[19]

Derivatives

[edit]

The bornyl group is a univalent radical C10H17 derived from borneol by removal of hydroxyl and is also known as 2-bornyl.[21] Isobornyl is the univalent radical C10H17 that is derived from isoborneol.[22] The structural isomer fenchol is also a widely used compound derived from certain essential oils.

Bornyl acetate is the acetate ester of borneol.

Notes and references

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Borneol

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from Grokipedia
Borneol is a bicyclic monoterpenoid alcohol with the molecular formula C₁₀H₁₈O and the IUPAC name 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol, existing naturally as two enantiomers: (+)-borneol (d-borneol) and (−)-borneol (l-borneol), while synthetic borneol is typically the . It features a camphor-like and a burning, mint-reminiscent , with physical properties including a of 202–209 °C, a of 210–212 °C, and low water solubility of approximately 0.74 g/L at 25 °C. Chemically, it is flammable and serves as a chiral building block in , often derived from the reduction of . First identified in 1842 by French chemist Charles Frédéric Gerhardt as "camphre de Bornéo" from Borneo-sourced resins, borneol has been extracted historically from the essential oils and resins of aromatic plants and trees. Its primary natural sources include the Borneo camphor tree (Dryobalanops aromatica), cinnamon species such as Cinnamomum burmanni and Cinnamomum camphora, and various essential oils from plants like rosemary (Salvia rosmarinus), ginger (Zingiber officinale), and frankincense (Boswellia sacra). Industrially, natural borneol is produced through steam distillation of these sources, while synthetic versions are produced from α-pinene (derived from turpentine) through isomerization to camphene, esterification, hydrolysis to isoborneol, and isomerization to borneol, or by reduction of camphor to isoborneol using agents like sodium borohydride followed by isomerization, addressing supply shortages of the natural product. Borneol holds significant applications in traditional Chinese medicine (TCM), where it is valued for its anti-inflammatory, analgesic, and blood-circulation-promoting properties, often used to treat conditions like pain, inflammation, and cardiovascular disorders. In modern contexts, it functions as a penetration enhancer for across the blood-brain barrier and mucosal tissues, improving the efficacy of therapeutics. Additionally, borneol is employed in perfumery and flavoring for its camphor-like, piney scent, appearing in fragrances, food additives, and products like rosemary-seasoned seasonings, though it requires careful handling due to its irritant potential and flammability.

Structure and properties

Chemical structure

Borneol is a bicyclic monoterpenoid alcohol with the molecular \ceC10H18O\ce{C10H18O}. Its core structure is based on the bornane skeleton, which is a bicyclo[2.2.1] system featuring at position 1 and dimethyl groups at the one-carbon bridge (position 7). A hydroxyl group is attached at the 2-position on the two-carbon bridge, defining it as a secondary alcohol. The systematic IUPAC name for the endo isomer, which is the predominant natural form, is (1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol. In bond-line notation, the structure is depicted as a fused ring system where carbons 1 and 4 serve as bridgeheads connected by two two-carbon bridges and one direct bond, with the hydroxyl oriented endo (toward the larger bridge) relative to the two-carbon bridges. The 3D representation of the bornane skeleton shows a rigid, envelope-like conformation similar to norbornane, with the C7 methylene bridge protruding above the plane formed by the bridgehead carbons and the two-carbon bridges, imparting strain and influencing the molecule's reactivity. The compound was first isolated and named by French chemist in 1842, who identified it as "camphre de Bornéo" from the resin of the tree Dryobalanops aromatica.

Physical and chemical properties

Borneol appears as a colorless to white solid, typically in the form of lumps, crystals, or powder, and possesses a pungent, camphor-like . Its is 154.25 g/mol, with a of 1.011 g/cm³ at 20 °C, a of 202–204 °C, and a of 210–212 °C. Borneol exhibits low solubility in water (approximately 0.738 g/L at 25 °C) but is readily soluble in organic solvents such as , , and . Under normal ambient conditions, borneol is chemically stable, though it is flammable and reacts with strong oxidizing agents to form . The enantiomers display optical rotations of +37° for d-borneol and -37° for l-borneol (in ethanol solution). In infrared (IR) , borneol is characterized by a broad O-H stretching band at approximately 3400 cm⁻¹, indicative of the alcohol . Key features in ¹H () spectroscopy include the methine proton adjacent to the hydroxyl group at around 4.0 ppm (multiplet), distinguishing it from the isoborneol . of borneol shows a molecular peak at m/z 154, with the base peak at m/z 95 resulting from loss of water and rearrangement.

Isomers and stereochemistry

Borneol possesses three chiral centers located at carbon atoms C1, C2, and C4 in its bicyclic structure, which theoretically permit up to eight stereoisomers; however, the rigid camphane skeleton restricts viable configurations, resulting in four principal stereoisomers consisting of two pairs of enantiomers for the endo and forms. The at C2 is particularly significant, defining the endo orientation of the hydroxyl group in borneol versus the exo orientation in its , isoborneol. These diastereomers share the same connectivity but differ in the relative spatial arrangement at C2, exemplified by the (1R,2S,4R)-configuration for (+)-borneol and analogous adjustments for its counterparts. The enantiomers of borneol are (+)-borneol, also denoted as d-borneol with the (1R,2S,4R), and (-)-borneol or l-borneol with (1S,2R,4S). Similarly, isoborneol exists as (+)-isoborneol and (-)-isoborneol enantiomers. In chemical synthesis, particularly via reduction of racemic , mixtures often yield racemic borneol alongside isoborneol, complicating separation due to similar physical properties. In nature, both enantiomers occur, with (+)-borneol sourced from plants in the family, such as Dryobalanops aromatica, and Valerianaceae, including species. The (-)-enantiomer predominates in essential oils from families like Compositae, Graminaceae, and Labiatae. This natural distribution often results in optically impure extracts, where the enantiomeric excess influences bioactivity; for instance, (-)-borneol has been shown to exhibit distinct immunomodulatory effects on neutrophils compared to its counterpart.

Occurrence and production

Natural sources

Borneol occurs naturally as a bicyclic alcohol primarily in the essential oils of various , where it contributes to their aromatic profiles and biological activities. The compound exists in both (+)- and (-)-enantiomeric forms, with natural sources yielding predominantly the D-(+)-borneol in certain species. Among the most significant plant sources is the Borneo camphor tree, Dryobalanops aromatica (), native to and classified as vulnerable due to for its , from which borneol can constitute up to 30% of the resinous exudate , though concentrations as high as 68% have been reported in oils. Other notable sources include Cinnamomum camphora (), particularly the borneol chemotype, where borneol levels in s range from 16% to 85%, depending on the variety and region. In Blumea balsamifera (), a widespread in , borneol comprises about 1-23% of the , serving as a key source for (-)-borneol extraction. Additional plant sources include Heterotheca inuloides (Asteraceae), known as Mexican arnica, where L-borneol is a major component in the flower and leaf essential oils from North and Central American species. Borneol is also present in essential oils of Artemisia species (Asteraceae), such as A. herba-alba and A. argyi, at levels of 5-18%, contributing to their medicinal properties in Mediterranean and Asian flora. Rosemary (Rosmarinus officinalis, Lamiaceae), a Mediterranean herb, contains borneol at 1-16% in its leaf essential oil. Similarly, the rhizomes of Kaempferia galanga (Zingiberaceae), an aromatic ginger from Southeast Asia, yield essential oils with 2.7-5% borneol. Geographically, borneol-rich plants are concentrated in , exemplified by D. aromatica in and , and C. camphora and B. balsamifera across , , and , though species like R. officinalis extend its distribution to the Mediterranean and H. inuloides to the . Trace amounts of borneol (0.1-5% in oils) have been detected in some fungi and insect exudates, but these are minor compared to plant-derived sources. Borneol is typically extracted from these natural sources via of leaves, resins, or rhizomes, a method that preserves its volatile nature and yields essential oils for further purification. Historically, borneol from D. aromatica was traded as "Borneo " from to and since ancient times, valued for its medicinal and preservative qualities. Biosynthetic enzymes like bornyl diphosphate synthase facilitate its production in these .

Biosynthesis

Borneol is biosynthesized in and microorganisms through the pathway, beginning with the condensation of (DMAPP) and isopentenyl pyrophosphate (IPP) to form (GPP). GPP then undergoes cyclization to bornyl pyrophosphate (BPP) catalyzed by bornyl diphosphate synthase, followed by of BPP to yield borneol. This pathway operates within the mevalonate (MVA) or methylerythritol phosphate (MEP) routes, depending on the organism, and is regulated as part of broader metabolism. Key enzymes in this process include monoterpene synthases such as (+)-bornyl diphosphate synthase, which facilitates the metal-dependent of GPP to (3R)-linalyl diphosphate and subsequent cyclization to (+)-BPP with high specificity. For instance, in , the enzyme produces (+)-BPP as 75% of its product from GPP. The subsequent dephosphorylation of BPP to borneol is mediated by , such as Nudix hydrolase WvNUDX24 in Wurfbainia villosa, which initiates the step and influences borneol accumulation. Similar synthases, like CbTPS1 from burmannii, exhibit kinetic parameters including a Km of 5.11 μM for GPP, underscoring their role in directing flux toward bicyclic monoterpenoids. Genes encoding these have been cloned and characterized, providing insights into regulation. In S. officinalis, the (+)-bornyl diphosphate gene corresponds to cDNA clone 3C6 (: AF051900), expressed as a homodimeric protein that stabilizes intermediates via cation-π interactions during cyclization. Expression of such is modulated by environmental factors and integrated into the MVA pathway, where upstream enzymes like influence precursor availability. In C. burmannii, the CbTPS1 (: MW196671) has been heterologously expressed to study pathway dynamics. Biosynthetic variations across species include differences in endo- versus exo-isomer production, with most plant synthases favoring the endo configuration of (+)-borneol through stereospecific PPi recapture in the active site. For example, BPPS from S. officinalis enforces endo specificity via structural constraints in its α-helical domains. Microbial engineering has enhanced yields by optimizing these pathways; in engineered Saccharomyces cerevisiae, co-expression of truncated BPS genes with MVA pathway modules and phosphatases increased (+)-borneol production by up to 96-fold to 2.89 mg/L. Further improvements, such as BPP dephosphorylation engineering, have achieved 33.8-fold titer boosts in yeast, demonstrating potential for scalable in vivo production.

Industrial synthesis

Industrial synthesis of borneol relies on chemical reductions and rearrangements, often starting from or pinenes derived from oil. In the early , processes emerged using as a feedstock, involving conversion of to borneol derivatives through acid-catalyzed reactions, enabling scalable production for commercial applications. Modern synthetic borneol achieves purity levels exceeding 98%, meeting pharmaceutical and fragrance industry standards. A primary method is the reduction of , a common precursor. The Meerwein–Ponndorf–Verley (MPV) reduction employs aluminum isopropoxide as a catalyst and isopropanol as a donor, converting to a of and isoborneol stereoisomers. This reversible process favors the exo alcohol (isoborneol) due to steric factors, typically yielding borneol in lower proportions within the mixture. Alternatively, (NaBH₄) reduction of in also produces a borneol/isoborneol mixture, with the reaction proceeding via delivery to the , though it is more prevalent in laboratory-scale preparations than large-scale operations. Another established route utilizes the Wagner–Meerwein rearrangement from , abundant in . undergoes acid-catalyzed isomerization to , followed by hydration or esterification to form isobornyl derivatives, which are then hydrolyzed to borneol. This pathway, involving migrations, supports efficient industrial conversion with high from renewable sources. Recent advancements focus on biocatalytic methods for enantioselective production, addressing limitations of chemical routes in stereocontrol. Engineered Saccharomyces cerevisiae expressing bornyl pyrophosphate synthase and pathway enzymes produces borneol at up to 23 mg/L in two-phase , demonstrating potential for scalable microbial synthesis. Similarly, whole-cell biocatalysts with engineered reduce (+)- to (+)-borneol under mild aqueous conditions (25 °C, 6.2), achieving 45% isolated yield and >99.5% diastereomeric excess on gram scales, suitable for high-purity pharmaceutical applications.

Chemical reactions

Oxidation reactions

Borneol, a bicyclic secondary alcohol, is readily oxidized to the corresponding , , through the loss of two atoms from the hydroxyl-bearing carbon at position 2. This transformation is a standard method for preparing and exemplifies the selective oxidation of secondary alcohols to s without affecting other functional groups in the structure. The overall reaction can be represented as: \ceC10H18O−>[oxidant]C10H16O+2H\ce{C10H18O ->[oxidant] C10H16O + 2H} Common oxidizing agents for this conversion include (as in the Jones reagent), (PCC), and the protocol. , typically used in acetone solution, provides efficient oxidation under mild conditions, yielding in high purity after . PCC, introduced by and , operates in at and is particularly selective for secondary alcohols, minimizing over-oxidation risks in sensitive substrates like borneol. The , employing dimethyl sulfoxide (DMSO), oxalyl chloride, and triethylamine, also proceeds under anhydrous, low-temperature conditions to deliver with excellent yields and is favored for its compatibility with acid-labile groups. The mechanism for these oxidations generally involves initial activation of the hydroxyl group, followed by abstraction from the adjacent carbon to form the carbonyl. In oxidations, the alcohol coordinates with the (VI) species to form a chromate intermediate, which undergoes rate-determining elimination of a , regenerating the oxidant and producing the . For PCC, the mechanism involves formation of a chromate intermediate, similar to oxidation, followed by elimination of a . For the , the pathway proceeds via a intermediate after activation of DMSO, ensuring clean conversion with retention of the bicyclic in the product, as the reaction does not alter the configuration at or other chiral centers. Mild conditions with these selective oxidants are crucial for borneol, preventing side reactions such as ring cleavage in the strained framework. This oxidation serves as a key intermediate step in the synthesis of various derivatives, where acts as a versatile precursor for further functionalizations, such as in the production of pharmaceuticals and fragrances derived from monoterpenes.

Reduction and esterification

Borneol can be produced through the reduction of , a related bicyclic , using aluminum () as the , which selectively delivers a to the , yielding the secondary alcohol borneol. This reduction typically generates a of stereoisomers, borneol (endo configuration) and isoborneol (exo configuration), with the exo product often predominating due to steric factors favoring hydride attack from the less hindered face of the . An alternative synthetic route involves the partial reduction of , a , to isoborneol, though this often proceeds via carbocation-mediated addition rather than direct transfer. Esterification of borneol is commonly achieved by reacting the alcohol with in the presence of an acid catalyst such as (H₂SO₄), forming bornyl as the primary product. This reaction follows the general mechanism of nucleophilic acyl substitution, where the hydroxyl group of borneol attacks the carbonyl of the anhydride, displacing . The balanced for this transformation is: C10H17OH+(CH3CO)2O→C10H17OCOCH3+CH3COOH\text{C}_{10}\text{H}_{17}\text{OH} + (\text{CH}_3\text{CO})_2\text{O} \rightarrow \text{C}_{10}\text{H}_{17}\text{OCOCH}_3 + \text{CH}_3\text{COOH} The acid catalyst protonates the carbonyl oxygen of the anhydride, enhancing its electrophilicity and facilitating the reaction, while also influencing ; in related additions, such conditions favor products due to the stability of the intermediate leading to the endo/ acetate isomers. This esterification preserves the stereochemistry of the starting borneol but can exhibit selectivity in mixtures of endo and alcohols. Bornyl acetate and related borneol esters find synthetic utility in the preparation of fragrances, where the compound imparts a characteristic piney, woody aroma used in perfumes, air fresheners, and personal care products. In pharmaceuticals, these esters serve as intermediates for derivatives exhibiting anti-inflammatory and antimicrobial properties, enhancing drug delivery or formulation stability. Note that esterification represents a reversible derivatization, contrasting with the oxidation of borneol to camphor.

Applications

Traditional and medicinal uses

In (TCM), borneol, known as Bingpian, is valued for its ability to clear heat, open sensory orifices, relieve pain, and serve as a carrier to enhance the delivery of other medicinal substances across biological barriers. It is classified as acrid, bitter, and cool in nature, entering the Heart, Lung, Liver, and Spleen meridians, and has been employed topically and internally for conditions involving , swelling, and neurological disturbances. A prominent example is its inclusion in the classical formulation Angong Niuhuang Wan, where it contributes to treating febrile diseases, coma, and disorders by promoting resuscitation and reducing heat. In Ayurvedic medicine, borneol, referred to as Pachha Karpooram, is utilized for its , , and properties, particularly to address respiratory issues such as and congestion. Similarly, in Japanese medicine, borneol supports analgesia and mild sedation, aiding in the management of pain and calming effects in prescriptions adapted from Chinese traditions. Historically, borneol has been employed across Asian cultures as an aromatic , often called "dragon's brain ," for and to alleviate digestive distress and fevers. In 19th-century Western contexts, it appeared in remedies akin to camphor-based treatments for respiratory ailments, including , due to its qualities. Borneol is commonly administered in crystalline form or as an , with typical oral doses in TCM ranging from 0.15 to 0.3 grams per day for synthetic varieties, or up to 0.9 grams for natural sources, often divided into multiple administrations.

Industrial and modern uses

Borneol serves as a key ingredient in the fragrance industry, where it imparts woody, camphoraceous, and pine-like notes, particularly in the form of l-borneol used to enhance perfumes, soaps, and detergents. It is incorporated into fine fragrances, shampoos, toiletries, and decorative cosmetics at low concentrations to provide a cooling, balsamic undertone, often in formulations mimicking rosemary or lavender scents. In the food sector, borneol functions as a generally recognized as safe (GRAS) flavoring agent by the U.S. FDA, contributing subtle spicy or herbal profiles to products such as spices, nuts, and beverages, typically at trace levels to avoid overpowering tastes. As an , borneol is formulated into topical products targeting mosquitoes, including , due to its natural deterrent properties derived from essential oils. It appears in commercial compositions at concentrations around 2-4% by weight, often combined with other like α-pinene for enhanced efficacy against biting . While direct synergy with has been explored in broader botanical repellents, borneol contributes to multi-component blends that extend protection duration. In modern , borneol acts as an in the combination edaravone dexborneol, where dexborneol (a form of (+)-borneol) facilitates penetration of the neuroprotective agent . The injectable form, Sanbexin®, received approval from China's (NMPA) in July 2020 for treating acute ischemic , marking it as a Class I innovative . A sublingual tablet version of Sanbexin® was subsequently approved by the NMPA in December 2024, offering improved neurological outcomes and functional recovery in patients with acute ischemic within 48 hours of onset. In August 2024, Sanbexin sublingual tablets received Designation from the U.S. (FDA) for the treatment of acute ischemic . Beyond these primary applications, borneol finds use in for its aromatic and soothing qualities in creams, lotions, and formulations, as well as in veterinary products where it enhances the of antibiotics like florfenicol for treating respiratory infections in animals.

Pharmacology and

Pharmacological activities

Borneol enhances the penetration of drugs across the blood-brain barrier (BBB) through a reversible, transient opening mechanism. Proposed mechanisms include alteration of tight junctions and downregulation of efflux transporters such as , thereby improving of co-administered agents like and nimustine. This property has been leveraged in to augment the delivery of therapeutics to the , facilitating targeted brain region access without permanent disruption to barrier integrity. In terms of and effects, borneol inhibits key pathways including COX-2 and , reducing proinflammatory release and mitigating inflammatory responses. Animal models of induced inflammation, such as for or , have shown borneol significantly decreases and pain behaviors by activating p38-COX-2-PGE2 signaling and disrupting TLR4/-mediated cycles. Borneol demonstrates moderate antimicrobial activity against bacteria like and fungi such as , primarily through disruption of cell membranes and formation. Minimum inhibitory concentrations (MICs) for these pathogens typically range from 0.5 to 2 mg/mL, with enhanced effects observed in combinations targeting preformed biofilms (33.7–58.2% inhibition at 0.25–4 mg/mL). Borneol provides neuroprotective benefits in ischemic models by reducing infarct and improving neurological outcomes, as evidenced by studies in rats where doses of 1.0 mg/kg decreased volume through anti-apoptotic and anti-necrotic mechanisms. Recent investigations from 2024–2025 highlight borneol's role in anti-influenza activity by inhibiting viral entry into host cells, particularly through modeling of borneol derivatives targeting replication. Clinically, the phase III TASTE trial (2021) demonstrated that dexborneol—a formulation incorporating the dextrorotatory of borneol—improved 90-day functional outcomes in acute ischemic patients compared to alone, with benefits linked to borneol's BBB modulation; this led to its approval in in 2024 and U.S. FDA designation in 2024. As of November 2025, full FDA approval is pending. Additionally, borneol exerts antioxidant effects by scavenging (ROS), inhibiting their generation in activated neutrophils and oxygen-glucose deprivation models to prevent oxidative neuronal damage.

Toxicity and safety

Borneol exhibits low acute oral , with an LD50 value of 5,800 mg/kg in rats. It may cause mild to the eyes and upon contact, as well as including to the and . Dermal exposure can lead to burns in severe cases, though borneol does not pose a significant risk for . High-dose exposure to borneol can result in symptoms such as , , , , and , potentially leading to loss of . While borneol modulates GABA receptors, potentially contributing to neurotoxic effects at elevated levels, no evidence indicates carcinogenicity, and it remains unclassified by the International Agency for Research on Cancer (IARC). Mild may occur in sensitive individuals upon skin contact, but patch testing supports its safety at concentrations up to 5% in cosmetic formulations. Borneol is recognized as generally regarded as safe (GRAS) by the U.S. (FDA) for use as a agent. In the , it is permitted in fragrances and without specific concentration limits beyond general good practices, though fragrance allergens are restricted to 0.01% in leave-on products when declarable. As of 2025, no new findings on have emerged, confirming its non-genotoxic profile, and clinical studies support its safety in combination therapies for acute ischemic at doses including up to 37.5 mg of dexborneol (a borneol ) twice daily.

Derivatives and recent research

Key derivatives

Borneol, a bicyclic alcohol with the formula C₁₀H₁₈O, serves as a precursor for several key derivatives through modifications such as esterification, , and oxidation. These derivatives retain the core bornane skeleton and are prepared via or substitution reactions on the hydroxyl group. The most common ester derivative is bornyl , formed by of borneol, with the molecular formula C₁₂H₂₀O₂. This compound features the bornyl group (C₁₀H₁₇-) esterified with acetic acid and is widely utilized in perfumes due to its balsamic, pine-like aroma. Bornyl chloride represents a key halogenated , obtained by substitution of the hydroxyl group with , yielding the C₁₀H₁₇Cl. It acts as an important synthetic intermediate in chemistry, often prepared from borneol using or . Oxidation of borneol produces , a bicyclic with the C₁₀H₁₆O, where the secondary alcohol is converted to a . This is typically synthesized using oxidizing agents like or . Other notable derivatives include bornyl isovalerate, an with the formula C₁₄H₂₄O₂ formed by reaction with isovaleric acid. The bornyl group itself (C₁₀H₁₇-) denotes the univalent radical derived from borneol by dehydroxylation and is used in IUPAC for naming related compounds.

Emerging research applications

Recent studies have explored N-butylphthalide (NBP)/borneol hybrids as potential neuroprotective agents for ischemic , demonstrating enhanced blood-brain barrier (BBB) penetration compared to NBP alone. In a 2025 investigation, these conjugates exhibited superior neuroprotective effects in cellular models of cerebral ischemia by improving to ischemic regions and reducing neuronal damage. Similarly, borneol-based polymeric micelles have shown promise in facilitating intracerebral for pathogenesis-adaptive treatment of ischemic , with improved BBB crossing via transient modulation of tight junctions. In chemoinformatics research from 2025, newly designed borneol-phenolic diterpenoid derivatives were identified as potential inhibitors of influenza A virus entry, particularly against the H1N1 strain (A/Puerto Rico/8/34). These hybrids displayed favorable binding affinities to viral hemagglutinin, suggesting mechanisms that block viral attachment and fusion with host cells, with predicted low toxicity profiles. Borneol esters synthesized in 2016 have demonstrated anti-inflammatory properties, with certain derivatives reducing edema in animal models. Additionally, borneol has been shown to enhance the cellular uptake of curcumin, improving its photodynamic fungicidal efficacy against Candida albicans. Borneol-modified nanoparticles have emerged in preclinical trials as enhancers for delivery to tumors, particularly . For instance, borneol-gastrodin liposomes co-administered intranasally with () reversed drug resistance by inhibiting efflux, achieving higher tumor accumulation and improved survival in glioma-bearing models. Likewise, borneol-modified micelles loaded with and tetrandrine, in a 2024 study, targeted drug-resistant gliomas, enhancing BBB permeation and inducing in tumor cells with reduced systemic toxicity. Other investigational efforts include antimicrobial hybrids combining borneol with (TCM) components, such as curcumin-loaded systems, which amplify photodynamic fungicidal effects against pathogens like through enhanced cellular uptake. Borneol-integrated hydrogels have also shown antibacterial and synergy in applications derived from TCM formulations. As of November 2025, no new borneol-based drugs from these emerging applications have received regulatory approval for clinical use.

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