84380-01-8

Basic information

• Product Name: alpha-Arbutin
• Synonyms: alpha-arbutin;4-hydroquinone-alpha-d-glucopyranoside;a-Arbutin;Hydroquinone O-α-D-Glucopyranoside;4-Hydroxyphenyl a-D-glucopyranoside;(2R,3S,4S,5R,6S)-2-(HYDROXYMETHYL)-6-(4-HYDROXYPHENOXY)TETRAHYDROPYRAN-3,4,5-TRIOL;4-hydroxyphenyl alpha-D-glucopyranoside;Alpha bear
• CAS NO: 84380-01-8
• Molecular Formula: C12H16O7
• Molecular Weight: 272.25
• EINECS: 209-795-0
• Product Categories: Plant extract;Aromatics;Carbohydrates & Derivatives;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 84380-01-8.mol

Chemical Properties

• Melting Point: 195-196°C
• Boiling Point: 561.6 °C at 760 mmHg
• Flash Point: 293.4 °C
• Appearance: /
• Density: 1.556 g/cm³
• Vapor Pressure: 1.9E-13mmHg at 25°C
• Refractive Index: 1.65
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 10.10±0.15(Predicted)
• BRN: 89675
• CAS DataBase Reference: alpha-Arbutin(CAS DataBase Reference)
• NIST Chemistry Reference: alpha-Arbutin(84380-01-8)
• EPA Substance Registry System: alpha-Arbutin(84380-01-8)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 84380-01-8(Hazardous Substances Data)

Usage

Uses

Used in Cosmetics Industry:
Alpha-Arbutin is used as a skin-whitening agent for its ability to reduce melanin production, resulting in a brighter and more even skin tone. It is particularly effective in treating sun spots, pigmentation, and scars caused by sun damage and breakouts.
Used in Skincare Products:
Alpha-Arbutin is used as an active ingredient in anti-aging products, where it works synergistically with Retinol to treat age spots, fine lines, and wrinkles. Its antioxidant properties also help protect the skin from potential sun damage.
Used in Analytical Chemistry:
Alpha-Arbutin may be used as an analytical reference standard for the determination of the analyte in cosmetics by high-performance liquid chromatography with UV detection (HPLC-UV) method. This allows for accurate measurement and quality control of cosmetic products containing Alpha-Arbutin.

benefits

Ensures an even skin tone after only one month;Reduces the degree of skin tanning after UV exposure;Helps to minimize the appearance of liver spots.

Biological Functions

Alpha arbutin acts as a tyrosinase competitive inhibitor and also slows melanosome maturation (the organelles that synthesize and store melanin or pigment).3 This is significant because it works on two different mechanisms of pigmentation. Melanin is derived from the amino acid tyrosine and this conversion is regulated by the enzyme tyrosinase. Alpha arbutin is similar in structure to tyrosine, which fits into tyrosinase, needed for melanogenesis. This means that alpha arbutin is reversibly competing with tyrosine for a spot on the enzyme and not inhibiting cell viability, so therefore is not cytotoxic. By targeting tyrosinase, the rate-limiting enzyme in melanin formation, as well as slowing production of the organelles that produce melanin, alpha arbutin is a potent skin brightening agent.

Mechanism of action

Alpha arbutin is frequently marketed as a safer alternative to hydroquinone (a popular skin-lightening ingredient that has been banned in Europe and Australia). It has similar results in brightening skin but without the dangerous bleaching process. Instead, it reduces skin’s pigment production by suppressing the enzymes that stimulate melanin. This also slows down the process by which UV light causes pigmentation, so it both prevents and treats pigmentation issues.

Synthesis

In a 100 ml reaction flask, add (1.21 g, 2.5 mmol)P-acetoxyphenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 6,Add 36 ml of anhydrous methanol to dissolve, magnetically stir, add a catalytic amount of 0.06 g of sodium methoxide, react at 25 ° C for 2 hours, add acidic resin to neutralize to system pH = 7,The resin was recovered by filtration, and the filtrate was concentrated to dryness under reduced pressure.Beta-arbutinWhite solid 0.65 g,The yield was 96%.

InChI:InChI=1/C12H16O7/c13-5-8-9(15)10(16)11(17)12(19-8)18-7-3-1-6(14)2-4-7/h1-4,8-17H,5H2/t8-,9-,10+,11-,12+/m1/s1

Upstream product

• 50-99-7 D-glucose 
• 123-31-9 hydroquinone 
• 57-50-1 Sucrose 
• 1668-09-3 maltopentaose 
• 2444-19-1 4-hydroxyphenyl benzoate 
• 69-79-4 D-maltose 
• 612802-12-7 O-p-acetoxyphenyl-2,3,4,6-tetra-O-acetyl-β-D-glucose 
• 439-03-2 2,3,4,6-tetra-O-acetyl-1-fluoro-α-D-glucopyranose 
• 352432-46-3 2,3,4,6-tetrakis-O-trimethylsilyl-α-D-glucopyranosyl iodide 
• 108534-47-0 4-(tert-butyldimethylsilyloxy)phenol 
• 3233-32-7 hydroquinone monoacetate 
• 103-16-2 4-Benzyloxyphenol 
• 83405-92-9 hydroquinone monobutyrate 
• 604-69-3 β-D-glucose pentaacetate 

Downstream Products

• 612802-12-7 O-p-acetoxyphenyl-2,3,4,6-tetra-O-acetyl-β-D-glucose 

Relevant articles and documents

Chemical synthetic method for beta-arbutin

The invention provides a chemical synthetic method for beta-arbutin, which includes: 1) performing a reaction to pentaacetyl-beta-D-glucose with a 70% hydrofluoric acid pyridine solution at 10-30 DEGC to obtain tetraacetyl-alpha-fluoroglucose; 2) performing a reaction to the tetraacetyl-alpha-fluoroglucose with p-hydroxyacetophenone in a mixed solvent under catalysis of tetrabutylammonium bromidewith Ca(OH)2 being an accelerant at 20-30 DEG C to prepare p-acetylphenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside; 3) performing a reaction to the p-acetylphenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside with 40% peroxyacetic acid in an organic solvent at 5-20 DEG C to obtain p-acetoxylphenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside; 4) performing a reaction to the p-acetoxylphenyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside at 15-25 DEG C in the presence of anhydrous methanol-sodium methoxide to obtain the beta-arbutin. The method is high in yield, low in cost, gentle in conditions and less in emission of waste liquid, waste gas and waste solids, and is suitable for industrial production.

A method of preparing α-arbutine

The invention provides a method for preparing alpha-arbutin. A glycosyl donor 2,3,4,6-tetra-O-trimethylsilyl-1-iodo-alpha-D-glucose, hydroquinone and its derivative undergo a glycosylation reaction, and protection groups are removed under acidic or alkaline conditions to obtain pure alpha-arbutin. Compared with present methods for preparing alpha-arbutin, the method has the advantages of realization of the synthesis of alpha-arbutin through a one-pot process, and high selectivity and high yield obtaining of alpha-arbutin under simple and mild conditions.

Enzymatic Glycosylation of Phenolic Antioxidants: Phosphorylase-Mediated Synthesis and Characterization

Although numerous biologically active molecules exist as glycosides in nature, information on the activity, stability, and solubility of glycosylated antioxidants is rather limited to date. In this work, a wide variety of antioxidants were glycosylated using different phosphorylase enzymes. The resulting antioxidant library, containing α/β-glucosides, different regioisomers, cellobiosides, and cellotriosides, was then characterized. Glycosylation was found to significantly increase the solubility and stability of all evaluated compounds. Despite decreased radical-scavenging abilities, most glycosides were identified to be potent antioxidants, outperforming the commonly used 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT). Moreover, the point of attachment, the anomeric configuration, and the glycosidic chain length were found to influence the properties of these phenolic glycosides.

Biphasic catalysis with disaccharide phosphorylases: Chemoenzymatic synthesis of α- D -glucosides using sucrose phosphorylase

Thanks to its broad acceptor specificity, sucrose phosphorylase (SP) has been exploited for the transfer of glucose to a wide variety of acceptor molecules. Unfortunately, the low affinity (Km > 1 M) of SP towards these acceptors typically urges the addition of cosolvents, which often either fail to dissolve sufficient substrate or progressively give rise to enzyme inhibition and denaturation. In this work, a buffer/ethyl acetate ratio of 5:3 was identified to be the optimal solvent system, allowing the use of SP in biphasic systems. Careful optimization of the reaction conditions enabled the synthesis of a range of α-d-glucosides, such as cinnamyl α-d-glucopyranoside, geranyl α-d-glucopyranoside, 2-O-α-d-glucopyranosyl pyrogallol, and series of alkyl gallyl 4-O-α-d-glucopyranosides. The usefulness of biphasic catalysis was further illustrated by comparing the glucosylation of pyrogallol in a cosolvent and biphasic reaction system. The acceptor yield for the former reached only 17.4%, whereas roughly 60% of the initial pyrogallol was converted when using biphasic catalysis.

Purification, characterization, and gene identification of an α-glucosyl transfer enzyme, a novel type α-glucosidase from Xanthomonas campestris WU-9701

The α-glucosyl transfer enzyme (XgtA), a novel type α-glucosidase produced by Xanthomonas campestris WU-9701, was purified from the cell-free extract and characterized. The molecular weight of XgtA is estimated to be 57 kDa by SDS-PAGE and 60 kDa by gel filtration, indicating that XgtA is a monomeric enzyme. Kinetic properties of XgtA were determined for α-glucosyl transfer and maltose-hydrolyzing activities using maltose as the α-glucosyl donor, and if necessary, hydroquinone as the acceptor. The Vmax value for α-glucosyl transfer activity was 1.3 × 10-2 (mM/s); this value was 3.9-fold as much as that for maltose-hydrolyzing activity. XgtA neither produced maltooligosaccharides nor hydrolyzed sucrose. The gene encoding XgtA that contained a 1614-bp open reading frame was cloned, identified, and highly expressed in Escherichia coli JM109 as the host. Site-directed mutagenesis identified Asp201, Glu270, and Asp331 as the catalytic sites of XgtA, indicating that XgtA belongs to the glycoside hydrolase family 13.

A new synthesis of α-arbutin via Lewis acid catalyzed selective glycosylation of tetra-O-benzyl-α-d-glucopyranosyl trichloroacetimidate with hydroquinone

α-Arbutin has huge application potentials in the cosmetic industry, as its inhibitory effect on human tyrosinase is stronger than that of its naturally occurring anomer arbutin (4-hydroxyphenyl β-d-glucopyranoside). Enzymatic synthesis was preferred for α-arbutin previously, and now a new chemical synthesis is reported. The reaction of tetra-O-benzyl-α-d-glucopyranosyl trichloroacetimidate, as glycosyl donor, with hydroquinone was initiated by catalytic amounts of trimethylsilyl trifluoromethanesulfonate (TMSOTf), resulting in 4-hydroxyphenyl 2,3,4,6-tetra-O-benzyl-α-d-glucopyranoside with high stereoselectivity and yield, and then to α-arbutin quantitatively after deprotection.

Syntheses of arbutin-α-glycosides and a comparison of their inhibitory effects with those of α-arbutin and arbutin on human tyrosinase

The effects of 4-hydroxyphenyl α-glucopyranoside (α-arbutin) and 4-hydroxyphenyl β-glucopyranoside (arbutin) on the activity of tyrosinase from human malignant melanoma cells were examined. The inhibitory effect of α-arbutin on human tyrosinase was stronger than that of arbutin. The Ki value for α-arbutin was calculated to be 1/20 that for arbutin. We then synthesized arbutin- α-glycosides by the transglycosylation reaction of cyclomaltodextrin glucanotransferase using arbutin and starch, respectively, as acceptor and donor molecules. The structural analyses using 13C- and 1H-NMR proved that the transglycosylated products were 4-hydroxyphenyl β-maltoside (β-Ab-α-G1) and 4-hydroxyphenyl β-maltotrioside (β-Ab-α-G2). These arbutin-α-glycosides exhibited competitive type inhibition on human tyrosinase, and their Ki values were calculated to be 0.7mM and 0.9mM, respectively. These arbutin-α-glycosides posessed stronger inhibitory activity than arbutin, but less activity than α-arbutin. These results suggested that the α-glucosidic linkage of hydroquinone-glycosides plays an important role in the inhibitory effect on human tyrosinase.

Effects of alpha- and beta-arbutin on activity of tyrosinases from mushroom and mouse melanoma.

The effects of alpha- and beta-arbutin on the activity of tyrosinases from mushroom and mouse melanoma were examined. alpha-Arbutin was synthesized from hydroquinone and starch using glucoside synthetase (GSase). beta-Arbutin inhibited both tyrosinase activities from mushroom and mouse melanoma. alpha-Arbutin inhibited only the tyrosinase from mouse melanoma, 10 times as strongly as beta-arbutin. The IC50 of alpha-arbutin was 0.48 mM and its inhibitory mechanism was speculated to be mixed type inhibition, while that of beta-arbutin was noncompetitive.

DIRECT CONDENSATION OF POLYHYDRIC PHENOLS WITH GLUCOSE

Acid-catalyzed direct condensation reaction of polyhydric phenols with free glucose in DMSO gave O-α-D-glucopyranoside in preference to its β-anomer; however, phloroglucinol and phloroacetophenone gave C-β-D-glucopyranoside instead.