60-81-1

Basic information

• Product Name: Phlorizin
• Synonyms: phlorrhizin;TIMTEC-BB SBB005924;PHLORIZIN HYDRATE;PHLORETIN-2'-BETA-D-GLUCOPYRANOSIDE DIHYDRATE;PHLORETIN-2'-BETA-D-GLUCOSIDE;PHLORETIN 2'-BETA-D-GLUCOSIDE DIHYDRATE;PHLORETIN-2'-O-GLUCOSIDE DIHYDRATE;PHLORIDZIN
• CAS NO: 60-81-1
• Molecular Formula: C₂₁H₂₄O₁₀
• Molecular Weight: 436.41
• EINECS: 200-487-1
• Product Categories: Chalcones;Biochemistry;Glucose;Glycosides;Sugars;Agro-Products;Carbohydrates & Derivatives;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 60-81-1.mol
• Article Data: 6

Chemical Properties

• Melting Point: 113-114 °C(lit.)
• Boiling Point: 468.89°C (rough estimate)
• Flash Point: 270.7 °C
• Appearance: Light yellow powder
• Density: 1.3178 (rough estimate)
• Refractive Index: -54 ° (C=3.2, 95% EtOH)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 7.15±0.40(Predicted)
• Merck: 14,7327
• CAS DataBase Reference: Phlorizin(CAS DataBase Reference)
• NIST Chemistry Reference: Phlorizin(60-81-1)
• EPA Substance Registry System: Phlorizin(60-81-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: UC2080000
• F: 3-10-23
• Hazardous Substances Data: 60-81-1(Hazardous Substances Data)

Usage

Summary

Phlorizin is the glucoside of phloretin. Its chemical name is 1- (2- (beta-D- glucopyranose oxygroup) -46- dihydroxy phenyl) -3- (4- hydroxycyclohexyl phenyl ketone) acetone, which belongs to dihydrochlcone of flavonoid. Phloridzin mainly exists in root barks, stems, leaflets and fruit of the apple tree, it can also be found in small amounts in the plants such as compositae, leguminosae, fagaceae, ericaceae, liliaceae and so on. It has many important biological activities, such as reducing blood sugar, improving memory, anti-allergy, anticancer, etc., as well as potential use values in food, beauty and health care products and other industry.

Distribution

Phloridzin exists mainly in Malus of Rosace, it has been reported in plants such as compositae, leguminosae, fagaceae, ericaceae, liliaceae and so on, but their amount is very low. In recent years, phlorizin is also found in litchi peel, leaves of pyrus betulaefolia, cynomorium songaricum, etc. though with a small amount. However, there are plenty of phloridzin in Lilhocarpus Polystachys Rehd. In general, the Malus plants are the main source of glucoside and can be used as the raw material to extract glucoside. Phloridzin is rich in branches, leaflets and barks of the apple tree. It can The distribution of phloridzin in apple fruits concentrate in seeds and rinds. The apple branches, leaves, bark and so on contain a large number of glucoside. The distribution of glucoside in apple fruit is concentrated on seeds and pericarp.

Extraction method

Material crushing: The dried branches or leaves of apple trees are crushed into coarse powders (10~20 mesh or 20~30 mesh). Extraction: Put pulverized crude powders into round flask, add 70% methanol for reflux extraction for 3 times, add 6, 4 and 4BV liquid independently, keep for 1h each time and combine the extracted solutions; (three extracts are brown to tan respectively). Inspissation: The antioxidant (VC) is added into the combined extract according to 0.2% of the total weight. Methanol can be recovered by reduced pressure distillation at 60℃.( The outcome solution is brownish turbid liquid) Removing impurities: Add polymerization alumina according to 0.5% of weight into the recovered concentrated solution without alcohol, adjust pH value to 7.5 with calcium hydroxide, put in the conical flask, hold 30min at 60℃, obtain the liquor after filtration; (flocculent is generated at the bottom after adding polymerization alumina) Extraction: the extraction condensate is cooled, the ethyl acetate is extracted with 1 times the ethyl acetate 3 times and the ethyl acetate solution is obtained; (the solution is stratified rapidly). Concentration: the ethyl acetate extract is decompressed and refluxed, concentrated to 10: 1, and the concentrated solution is obtained. Purification: Dissolve the concentrated liquid with 40% methanol, filter, place the filtrate for 24h, get the crystallization after extraction filtration, obtain the phlorizin by prevailing pressure drying or reducing pressure drying. (yellow powder) The activated carbon is used to decolorize the crude products because its decolorization principle is physical adsorption without damage to the biological activity of the root bark. The activated carbon is dried in a vacuum drying box to be activated. Then the activated carbon is added into aqueous solutions of crude products. The supernatant liquid can be obtained after stir and filtration. The liquid is placed to crystalize under natural conditions and the white needle crystal occurs eventually. Figure 1. the p technological process of the phlorizin extraction

Synthetic method

The precusor substance used to synthetize phlorizin is Malonyl-CoA and p-coumaroyl-CoA. Firstly, we use p-coumaroyl-CoA to generate 4-hydroxydihydrocinnamoyl-CoA by NADPH; then, phloretin is synthesized by Malonyl-CoA and 4-hydroxydihydrocinnamoyl-CoA under the action of tecatone synthetase; finally, phloridzin is generated by phloretin glucosylation. The overviews, extraction methods and synthesis methods of the phlorizin are compiled by Shi yan of lookchem. (2015-12-02)

Biological activity

Hypoglycemic effect Diabetes is a major disease that threatens human health and its typical symptom is hyperglycemia. Now the main drugs for the treatment of diabetes include traditional sulfonylurea, metformin and some new hypoglycemic agents such as rosiglitazone, pioglitazone, etc. The mechanisms of action are mostly used to promote insulin secretion or increase insulin sensitivity. A large number of studies have shown that phlorizin has the effect of reducing fasting blood glucose. The mechanism of decreasing glucose is competitively inhibiting the transport of glucose molecules on glucose transporters (SGLTs and GLUTs). Antioxidation Phlorizin has obvious protective effects on oxidative damage induced by high-fat diet in drosophila, as well as strong antioxidant effect, and enhance the activity of SOD and CAT to prolong life spans of drosophila significantly. The physiological relationship with plants. Phlorizin is closely related to the growth and stress resistance and other physiological phenomena of plants. It can resist various pathogenic bacterias, such as apple scab, fire blight, etc. However, it may inhibit the growth of some plants. Low concentration of phlorizin can promote the growth of Pingyi sweet tea seedlings, but high concentration will cause plant replant disorders. Phlorizin can promote the regeneration of papaya embryos and stimulate the root growth particularly. Therefore, as a plant growth regulator, its dosage is the key factor. Other activities In addition to antidiabetics, antioxidant and other biological activities, phlorizin has effects of anti-inflammatory, anti-cancer and so on.

Application

It has many important biological activities, such as reducing blood sugar, improving memory, anti allergy, anticancer, etc., as well as potential use values in food, beauty and health care products and other industry. Food Phlorizin has been approved as a kind of food additive. It is a characteristic phenolic substance in apple. Due to species, producers and other issues, the contents of phlorizin in different apples are quite different. Therefore, its content can be used as an index to distinguish the producers and qualities of apple juice. Phlorizin can promote the absorption and utilization of genistein (inhibit the growth and metastasis of tumor cells). It has a broad market in prevention and treatment of cancer to develop functional foods which rich in phlorizin and genistein. It is a high sweet natural sweetener, which can be used as an alternative food for diabetic patients. After phlorizin is oxidized by polyphenol oxidase, the products can be converted into bright yellow dyes. The dye has strong water solubility and can be used in food processing industry instead of artificial dyes to avoid the toxic effects caused by synthetic pigments. It has potential application values in the development and utilization either as a kind of food additive or as a functional food. Medicine As phlorizin is easily hydrolyzed in human body to yield the phloretin and has lower intestinal absorption rate, it is often designed to be high molecular polymer for the development of drugs with other compounds. Cosmetics The antioxidant activity and antiaging function of phlorizin have been confirmed by modern scientific researches. The hydrolysate of phlorizin, which is called phloretin, can inhibit the tyrosinase activity competitively and interfere the synthesis of melanin. Its whitening effect is better than many whitening products on the market. However, it is important to note that phlorizin increases the expression of tyrosinase genes by activating the cAMP signaling pathway, which leads to the formation of melanin.

Chemical Properties

Light Yellow Powder

Uses

Different sources of media describe the Uses of 60-81-1 differently. You can refer to the following data:
1. It is a dihydrochalcone occurring in all parts of the apple tree except the mature fruit. Once thought to occur in pear, plum, cherry trees and other Rosaceae
2. induces experimental glucosuria, antifeedant
3. Sodium-glucose cotransporter 1 (SGLT1) is a high affinity, low capacity transporter abundant in the small intestine, with some expression in the kidney as well. SGLT2 is a low affinity, high capacity transporter in the kidney that accounts for approximately 90% of glucose reabsorption into the blood stream. Selective inhibition of SGLT2 is a potential strategy for reducing plasma glucose levels as a treatment for diabetes. Phlorizin is a natural product, first isolated from the bark of apple trees, that reduces plasma glucose levels by blocking renal and intestinal glucose absorption through inhibition of SGLT1 and SGLT2. It competitively inhibits the initial rate of a-methyl-D-glucopyranoside (a-MDG) uptake in human COS-1 cells expressing hSGLT1 and hSGLT2 with IC50 values of 400 and 65 nM, respectively. In HEK293T cells expressing human SGLT1 and SGLT2, phlorizin exhibits Ki values of 140 and 11 nM, respectively, at 37°C.

Definition

ChEBI: An aryl beta-D-glucoside that is phloretin attached to a beta-D-glucopyranosyl residue at position 2' via a glycosidic linkage.

Purification Methods

-D-glucoside] [60-81-1] M 472.5, m 110o, [] 20 -62o (c 3.2, EtOH). Phlorizin crystallises as the dihydrate from water and causes glycosuria. [Brazy & Dennis Am J Physiol 234 1279 1978, Zemplen & Bognár Chem Ber 17B 1040 1943, Beilstein 17/7 V 177.]

Upstream product

• 4547-85-7 4,2',4',6'-tetrahydroxychalcone 6'-O-β-D-glucoside 
• 23711-00-4 naringenin-5-O-glucoside 
• 572-10-1 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl chloride 
• 130471-79-3 4-O-Benzoylphloracetophenone 2-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside) 
• 130471-75-9 ο-Benzoyloxy-phloracetophenon 
• 4547-85-7 2,4,4',6-Tetrahydroxychalcone 2'-O-α-D-mannopyranoside 
• 60-82-2 3-(4-Hydroxy-phenyl)-1-(2,4,6-trihydroxy-phenyl)-propan-1-on 
• 952585-00-1 uridine-5'-diphosphoglucose 
• 133-89-1 UDP-glucose 
• 123-08-0 4-hydroxy-benzaldehyde 

Downstream Products

• 11075-15-3 2',4,6'-trihydroxy-4'-methoxydihydrochalcone 2'-O-β-D-glucopyranoside 
• 133-89-1 UDP-glucose 
• 60-82-2 3-(4-Hydroxy-phenyl)-1-(2,4,6-trihydroxy-phenyl)-propan-1-on 
• 23140-78-5 4,4'-dihydroxy-dihydrochalcone-2'-O-β-D-glucopyranoside 
• 1620631-21-1 1,1'-[methylenebis(2,4,6-trihydroxy-3,1-phenylene)]bis[3-(4-hydroxyphenyl)propan-1-one] 
• 11023-94-2 1-[3-(β-D-glucopyranosyl)-2,4,6-trihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one 
• 286382-93-2 2'-phosphophloretin 
• 1333219-92-3 2'-fluorophosphophloretin 
• 1333219-93-4 dibenzylphosphotribenzylphloretin 
• 1421589-35-6 (6-{3,5-dihydroxy-2-[3-(4-hydroxyphenyl)propanoyl]phenoxy}-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,16,19-docosahexaenoate 

Relevant articles and documents

Molecular and Structural Characterization of a Promiscuous C-Glycosyltransferase from Trollius chinensis

Herein, the catalytic promiscuity of TcCGT1, a new C-glycosyltransferase (CGT) from the medicinal plant Trollius chinensis is explored. TcCGT1 could efficiently and regio-specifically catalyze the 8-C-glycosylation of 36 flavones and other flavonoids and could also catalyze the O-glycosylation of diverse phenolics. The crystal structure of TcCGT1 in complex with uridine diphosphate was determined at 1.85 ? resolution. Molecular docking revealed a new model for the catalytic mechanism of TcCGT1, which is initiated by the spontaneous deprotonation of the substrate. The spacious binding pocket explains the substrate promiscuity, and the binding pose of the substrate determines C- or O-glycosylation activity. Site-directed mutagenesis at two residues (I94E and G284K) switched C- to O-glycosylation. TcCGT1 is the first plant CGT with a crystal structure and the first flavone 8-C-glycosyltransferase described. This provides a basis for designing efficient glycosylation biocatalysts.

Towards the synthesis of glycosylated dihydrochalcone natural products using glycosyltransferase-catalysed cascade reactions

Regioselective O-β-D-glucosylation of flavonoid core structures is used in plants to create diverse natural products. Their prospective application as functional food and pharmaceutical ingredients makes flavonoid glucosides interesting targets for chemical synthesis, but selective instalment of a glucosyl group requires elaborate synthetic procedures. We report glycosyltransferase-catalysed cascade reactions for single-step highly efficient O-β-D-glucosylation of two major dihydrochalcones (phloretin, davidigenin) and demonstrate their use for the preparation of phlorizin (phloretin 2′-O-β-d-glucoside) and two first-time synthesised natural products, davidioside and confusoside, obtained through selective 2′- and 4′-O-β-d-glucosylation of the dihydroxyphenyl moiety in davidigenin, respectively. Parallel biocatalytic cascades were established by coupling uridine 5′-diphosphate (UDP)-glucose dependent synthetic glucosylations catalysed by herein identified dedicated O-glycosyltransferases (OGTs) to UDP dependent conversion of sucrose by sucrose synthase (SuSy; from soybean). The SuSy reaction served not only to regenerate the UDP-glucose donor substrate for OGT (up to 9 times), but also to overcome thermodynamic restrictions on dihydrochalcone β-d-glucoside formation (up to 20% conversion and yield enhancement). Using conditions optimised for overall coupled enzyme activity, target 2′-O- or 4′-O-β-d-glucoside was obtained in ≥88% yield from reactions consisting of 5 mM dihydrochalcone acceptor, 100 mM sucrose, and 0.5 mM UDP. Davidioside and confusoside were isolated and their proposed chemical structures confirmed by NMR. OGT-SuSy cascade transformations present a green chemistry approach for efficient glucosylation in natural products synthesis. the Partner Organisations 2014.

Cosmetic composition

A composition for topical application to the skin in order to promote the repair of photo-damaged or aged skin and/or to reduce or prevent damaging effects of ultra-violet light on skin and/or to lighten the skin comprising a hydrocalchone of general structure: STR1 wherein R1, R2 and R3, which may be the same or different, represent H, --OH, --OR or --COR (where R is a C1-20 alkyl group); R4, R5, R6 and R7, which may be the same or different, represent H or --COR (where R is as herein before defined). Optional additional ingredients include sunscreens and other skin lightening skin lightening agents, particularly retinol or derivatives thereof.