3542-72-1

Basic information

• Product Name: norathyriol
• Synonyms: norathyriol;1,3,6,7-Tetrahydroxy-9H-xanthen-9-one;1,3,6,7-Tetrahydroxyxanthone;Mangiferitin;rathyriol;9H-Xanthen-9-one, 1,3,6,7-tetrahydroxy-
• CAS NO: 3542-72-1
• Molecular Formula: C13H8O6
• Molecular Weight: 260.2
• Mol File: 3542-72-1.mol
• Article Data: 14

Chemical Properties

• Melting Point: 320 °C
• Boiling Point: 595.1°Cat760mmHg
• Flash Point: 237.8°C
• Appearance: /
• Density: 1.766g/cm³
• Vapor Pressure: 9.28E-15mmHg at 25°C
• Refractive Index: 1.801
• PKA: 6.68±0.20(Predicted)
• CAS DataBase Reference: norathyriol(CAS DataBase Reference)
• NIST Chemistry Reference: norathyriol(3542-72-1)
• EPA Substance Registry System: norathyriol(3542-72-1)

Safety Data

• Hazardous Substances Data: 3542-72-1(Hazardous Substances Data)

Usage

Definition

ChEBI: A member of the class of xanthones that is 9H-xanthen-9-one substituted by hydroxy groups at positions 1, 3, 6 and 7. Isolated from Garcinia mangostana and Maclura pomifera, it exhibits inhibitory activity again t protein kinase C.

InChI:InChI=1/C13H8O6/c14-5-1-9(17)12-11(2-5)19-10-4-8(16)7(15)3-6(10)13(12)18/h1-4,14-17H

Synthetic route

1,3,6,7-tetramethoxy-9H-xanthen-9-one (3542-74-3) → norathyriol (3542-72-1)

Conditions	Yield
With hydrogen iodide In various solvent(s) at 160℃; for 8h;	94%
With pyridine hydrochloride at 180℃; for 4.5h; Inert atmosphere;	85%
With hydrogen bromide In water; acetone for 24h; Reflux; Inert atmosphere;	50%
With hydrogen iodide
With pyridine hydrochloride

C21H18O11 → norathyriol (3542-72-1)

Conditions	Yield
Stage #1: C21H18O11 With trifluoroacetic anhydride In dichloromethane at 20 - 23℃; for 0.5h; Inert atmosphere; Stage #2: With boron trifluoride diethyl etherate In dichloromethane at 20 - 23℃; for 2h; Inert atmosphere; Stage #3: With methanol; potassium carbonate at 20 - 23℃; for 12h; Inert atmosphere;	87%

acide 2,4,6-trihydroxybenzoique (83-30-7) + benzene-1,2-diol (120-80-9) → norathyriol (3542-72-1)

Conditions	Yield
With zinc(II) chloride; trichlorophosphate at 75℃; for 0.5h; Microwave irradiation;	74.1%

mangiferin (4773-96-0) → norathyriol (3542-72-1)

Conditions	Yield
With hydrogen iodide; phenol for 7h; Heating;	43%
With hydrogenchloride; recorcinol In water for 6h; Reagent/catalyst; Reflux;
With hydrogenchloride; recorcinol In water at 150℃; for 6h; Reagent/catalyst; Green chemistry;

maclurin (519-34-6) → norathyriol (3542-72-1)

Conditions	Yield
With culture biomass of Rhodotorula buffonii In aq. phosphate buffer; N,N-dimethyl-formamide for 24h; Time; Microbiological reaction; Heating;	25.52%
Stage #1: maclurin With potassium carbonate In water Cooling with ice; Stage #2: With potassium hexacyanoferrate(III) In water at 20℃; for 5h; Inert atmosphere; Cooling with ice;	25.7%

1,3,6,7-tetrahydroxyxanthone acetate (2054-37-7) → norathyriol (3542-72-1)

Conditions	Yield
With hydrogenchloride
With sulfuric acid

isomangiferin (24699-16-9) → norathyriol (3542-72-1)

Conditions	Yield
With hydrogen iodide; phenol at 150℃; for 5h; labelled comp.;

1,3,7-trihydroxy-6-methoxyxanthone (59092-97-6) → norathyriol (3542-72-1)

Conditions	Yield
With hydrogen iodide for 2.5h; Heating; labelled comp.; Yield given;

2-D-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one (906328-94-7) → norathyriol (3542-72-1)

Conditions	Yield
With hydrogen iodide; phenol at 150℃; for 5h; labelled comp.;

2,4,5-trimethoxybenzoyl chloride (42833-66-9) → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) AlCl3, 2.) pyridine, 10percent aq. tetramethylammonium hydroxide / 1.) diethyl ether, RT, 8 h, 2.) reflux, 36 h 2: 94 percent / HI / various solvent(s) / 8 h / 160 °C View Scheme
Multi-step reaction with 3 steps 1: aluminum (III) chloride / diethyl ether / 48 h / 20 °C 2: pyridine; tetra(n-butyl)ammonium hydroxide / water / 4 h / Reflux 3: pyridine hydrochloride View Scheme

asaronic acid (490-64-2) → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: oxalyl chloride / benzene / 2 h / Ambient temperature 2: 1.) AlCl3, 2.) pyridine, 10percent aq. tetramethylammonium hydroxide / 1.) diethyl ether, RT, 8 h, 2.) reflux, 36 h 3: 94 percent / HI / various solvent(s) / 8 h / 160 °C View Scheme
Multi-step reaction with 4 steps 1: thionyl chloride / Reflux 2: aluminum (III) chloride / diethyl ether / 48 h / 20 °C 3: pyridine; tetra(n-butyl)ammonium hydroxide / water / 4 h / Reflux 4: pyridine hydrochloride View Scheme
Multi-step reaction with 2 steps 1.1: thionyl chloride / dichloromethane / 10 h / Reflux 1.2: 10 h / 0 °C / Reflux 1.3: 12 h / Reflux 2.1: hydrogen bromide / acetone; water / 24 h / Reflux; Inert atmosphere View Scheme

2,5-dihydroxy-4-methoxybenzoic acid (5981-37-3) → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: fused ZnCl2, POCl3 / 2 h / 70 °C 2: HI (d=1.7) / 2.5 h / Heating; labelled comp. View Scheme

xanthene-1,3,6,7-tetraol (105904-53-8) → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 3 steps 2: chromium (VI)-oxide; acetic acid; acetic acid anhydride 3: concentrated sulfuric acid View Scheme
Multi-step reaction with 3 steps 2: chromium (VI)-oxide; acetic acid; acetic acid anhydride 3: aq.-ethanolic hydrochloric acid View Scheme

1,3,6,7-tetraacetoxy-xanthene (102478-32-0) → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: chromium (VI)-oxide; acetic acid; acetic acid anhydride 2: concentrated sulfuric acid View Scheme
Multi-step reaction with 2 steps 1: chromium (VI)-oxide; acetic acid; acetic acid anhydride 2: aq.-ethanolic hydrochloric acid View Scheme

2,4,6-trimethoxy-2'-hydroxy-4',5'-dimethoxybenzophenone (42833-68-1) → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine; tetra(n-butyl)ammonium hydroxide / water / 4 h / Reflux 2: pyridine hydrochloride View Scheme

4-methyl-1,2-dihydroxybenzene (452-86-8) → norathyriol (3542-72-1)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: sodium periodate / dichloromethane; water / 1 h / 20 - 23 °C 2.1: N,N'-di-tert-butylethylenediamine; oxygen; copper(l) chloride / dichloromethane / 0.83 h / 20 - 23 °C / 1520.1 Torr 3.1: sodium dithionite / water / 0.5 h / 20 - 23 °C / Inert atmosphere 4.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 4 h / 80 °C / Inert atmosphere 4.2: 12 h / 20 - 23 °C / Inert atmosphere 5.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 6.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 6.2: 2 h / 20 - 23 °C / Inert atmosphere 6.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

4-methylbenzo-1,2-quinone (3131-54-2) → norathyriol (3542-72-1)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: N,N'-di-tert-butylethylenediamine; oxygen; copper(l) chloride / dichloromethane / 0.83 h / 20 - 23 °C / 1520.1 Torr 2.1: sodium dithionite / water / 0.5 h / 20 - 23 °C / Inert atmosphere 3.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 4 h / 80 °C / Inert atmosphere 3.2: 12 h / 20 - 23 °C / Inert atmosphere 4.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 5.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 5.2: 2 h / 20 - 23 °C / Inert atmosphere 5.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

5-hydroxy-1,3-phenylene diacetate (116345-96-1) → norathyriol (3542-72-1)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: N,N'-di-tert-butylethylenediamine; oxygen; copper(l) chloride / dichloromethane / 0.83 h / 20 - 23 °C / 1520.1 Torr 2.1: sodium dithionite / water / 0.5 h / 20 - 23 °C / Inert atmosphere 3.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 4 h / 80 °C / Inert atmosphere 3.2: 12 h / 20 - 23 °C / Inert atmosphere 4.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 5.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 5.2: 2 h / 20 - 23 °C / Inert atmosphere 5.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

C17H14O7 → norathyriol (3542-72-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: sodium dithionite / water / 0.5 h / 20 - 23 °C / Inert atmosphere 2.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 4 h / 80 °C / Inert atmosphere 2.2: 12 h / 20 - 23 °C / Inert atmosphere 3.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 4.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 4.2: 2 h / 20 - 23 °C / Inert atmosphere 4.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

C21H20O9 → norathyriol (3542-72-1)

Conditions

Yield

Multi-step reaction with 3 steps 1.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 4 h / 80 °C / Inert atmosphere 1.2: 12 h / 20 - 23 °C / Inert atmosphere 2.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 3.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 3.2: 2 h / 20 - 23 °C / Inert atmosphere 3.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

C21H18O10 → norathyriol (3542-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 2.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 2.2: 2 h / 20 - 23 °C / Inert atmosphere 2.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

3,5-dihydroxyphenol (108-73-6) → norathyriol (3542-72-1)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: pyridine / 12 h / 20 - 23 °C 1.2: 24 h / 20 - 23 °C 2.1: N,N'-di-tert-butylethylenediamine; oxygen; copper(l) chloride / dichloromethane / 0.83 h / 20 - 23 °C / 1520.1 Torr 3.1: sodium dithionite / water / 0.5 h / 20 - 23 °C / Inert atmosphere 4.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 4 h / 80 °C / Inert atmosphere 4.2: 12 h / 20 - 23 °C / Inert atmosphere 5.1: sodium dihydrogenphosphate; sodium chlorite / water; dimethyl sulfoxide / 2 h / 20 - 23 °C 6.1: trifluoroacetic anhydride / dichloromethane / 0.5 h / 20 - 23 °C / Inert atmosphere 6.2: 2 h / 20 - 23 °C / Inert atmosphere 6.3: 12 h / 20 - 23 °C / Inert atmosphere View Scheme

norathyriol (3542-72-1) + chloromethyl methyl ether (107-30-2) → 1-hydroxy-3,6,7-tris(methoxymethoxy)-9H-xanthen-9-one (1314917-55-9)

Conditions	Yield
Stage #1: norathyriol With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.25h; Stage #2: chloromethyl methyl ether at 0 - 20℃; for 10h;	81.6%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 8h; Inert atmosphere;

norathyriol (3542-72-1) + benzyl bromide (100-39-0) → 3,6,7-tris(benzyloxy)-1-hydroxy-9H-xanthen-9-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 40℃; for 4h;	68%

norathyriol (3542-72-1) + 2-methylbenzyl bromide (89-92-9) → 1,6,7-trihydroxy-3-((2-methylbenzyl)oxy)-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	49.2%

1-bromomethyl-3-methyl-benzene (620-13-3) + norathyriol (3542-72-1) → 1,6,7-trihydroxy-3-((3-methylbenzyl)oxy)-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	48.1%

norathyriol (3542-72-1) + 1-(Bromomethyl)-3-fluorobenzene (456-41-7) → 3-((3-fluorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	44.8%

1-(bromomethyl)-3-chloro-2-fluorobenzene + norathyriol (3542-72-1) → 3-((3-chloro-2-fluorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	41.6%

o-fluorobenzyl bromide (446-48-0) + norathyriol (3542-72-1) → 3-((2-fluorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	36.4%

norathyriol (3542-72-1) + 1-bromomethyl-2-chlorobenzene (611-17-6) → 3-((2-chlorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	35.4%

norathyriol (3542-72-1) + 4-Fluorobenzyl bromide (459-46-1) → 3-((4-fluorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	34.8%

norathyriol (3542-72-1) + 4-Methylbenzyl bromide (104-81-4) → 1-hydroxy-3,6,7-tris((4-methylbenzyl)oxy)-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	33.5%

norathyriol (3542-72-1) + 4-chlorobenzyl bromide (622-95-7) → 3-((4-chlorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	32.8%

norathyriol (3542-72-1) + 1-bromomethyl-3-chlorobenzene (766-80-3) → 3-((3-chlorobenzyl)oxy)-1,6,7-trihydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	32.8%

norathyriol (3542-72-1) + 4-chlorobenzyl bromide (622-95-7) → 3,6,7-tris((4-chlorobenzyl)oxy)-1-hydroxy-9H-xanthen-9-one

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide at 80℃; for 7h;	21.6%

diazomethane (186581-53-3, 908094-01-9) + norathyriol (3542-72-1) → 1-hydroxy-3,6,7-trimethoxyxanthone (2054-36-6)

Conditions	Yield
With diethyl ether

norathyriol (3542-72-1) + acetic anhydride (108-24-7) → 1,3,6,7-tetrahydroxyxanthone acetate (2054-37-7)

Conditions	Yield
With sulfuric acid
With sodium acetate for 2h; Heating; labelled comp.; Yield given;
With pyridine for 24h;

norathyriol (3542-72-1) → xanthene-1,3,6,7-tetraol (105904-53-8)

Conditions	Yield
With palladium on activated charcoal; ethanol Hydrogenation;

chlorobromomethane (74-97-5) + norathyriol (3542-72-1) → 1,3-Dihydroxy-6,7-methylenedioxyxanthone (14103-14-1)

Conditions	Yield
With potassium carbonate 1) acetone, reflux, 1 h, 2) reflux, 16 h; Yield given. Multistep reaction;

norathyriol (3542-72-1) → 3,5-dihydroxyphenol (108-73-6)

Conditions	Yield
With potassium hydroxide; sodium hydroxide at 290 - 300℃; for 1h; labelled comp.;

Upstream product

• 906328-94-7 2-D-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one 
• 102478-32-0 1,3,6,7-tetraacetoxy-xanthene 
• 83-30-7 acide 2,4,6-trihydroxybenzoique 
• 120-80-9 benzene-1,2-diol 
• 108-73-6 3,5-dihydroxyphenol 
• 116345-96-1 5-hydroxy-1,3-phenylene diacetate 
• 3131-54-2 4-methylbenzo-1,2-quinone 
• 452-86-8 4-methyl-1,2-dihydroxybenzene 
• 519-34-6 maclurin 
• 42833-68-1 2,4,6-trimethoxy-2'-hydroxy-4',5'-dimethoxybenzophenone 
• 105904-53-8 xanthene-1,3,6,7-tetraol 
• 5981-37-3 2,5-dihydroxy-4-methoxybenzoic acid 
• 490-64-2 asaronic acid 
• 42833-66-9 2,4,5-trimethoxybenzoyl chloride 

Downstream Products

• 519-34-6 maclurin 
• 1314917-78-6 C₂₇H₂₈O₉ 
• 1314917-79-7 C₂₆H₂₅FO₉ 
• 1314917-80-0 C₂₆H₂₅FO₉ 
• 1314917-81-1 C₂₆H₂₅FO₉ 
• 1314917-82-2 C₂₆H₂₅ClO₉ 
• 1314917-83-3 C₂₆H₂₅ClO₉ 
• 1314917-84-4 C₂₆H₂₅ClO₉ 
• 1314917-85-5 C₂₆H₂₅BrO₉ 
• 1314917-86-6 C₂₆H₂₅BrO₉ 
• 1314917-87-7 C₂₆H₂₅BrO₉ 
• 1314917-88-8 C₂₆H₂₅NO₁₁ 
• 1314917-89-9 C₂₆H₂₅NO₁₁ 
• 1314917-90-2 C₂₆H₂₅NO₁₁ 

Relevant articles and documents

An Improved C-Deglycosylation of Mangiferin to Norathyriol

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A novel and efficient synthesis of norathyriol using Pd(II) as a catalyst

A facile and simple procedure for the synthesis of norathyriol using Pd(II) as a catalyst via two steps under mild conditions is described. The major advantages of this method are the use of a commercially available catalyst, short reaction times, and the simplicity of the reaction and work-up. The overall yield of 36.6 % is acceptable.

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Studies on the constituents of Swertia japonica. V. On the xanthone constituents of the plants of Swertia ssp

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Design, synthesis, and biological evaluation of 1,3,6,7-tetrahydroxyxanthone derivatives as phosphoglycerate mutase 1 inhibitors

Phosphoglycerate mutase 1 (PGAM1) is a promising target for cancer treatment. Herein, we found that α-mangostin and γ-mangostin exhibited moderate PGAM1 inhibitory activities, with IC50 of 7.2 μM and 1.2 μM, respectively. Based on α-mangostin, a series of 1,3,6,7-tetrahydroxyxanthone derivatives were designed, synthesized and evaluated in vitro for PGAM1 inhibition. The significant structure–activity relationships (SAR) and a fresh binding mode of this kind of new compounds were also clearly described. This study provides valuable information for further optimization of PGAM1 inhibitors with 1,3,6,7-tetrahydroxyxanthone backbone or de novo design of novel inhibitor.

Synthesis of xanthone derivatives and studies on the inhibition against cancer cells growth and synergistic combinations of them

34 Xanthones were synthesized by microwave assisted technique. Their in?vitro inhibition activities against five cell lines growth were evaluated. The SAR has been thoroughly discussed. 7-Bromo-1,3-dihydroxy-9H-xanthen-9-one (3-1) was confirmed as the most active agent against MDA-MB-231?cell line growth with an IC50 of 0.46?±?0.03?μM. Combination of 3-1 and 5,6-dimethylxanthone-4-acetic acid (DMXAA) showed the best synergistic effect. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for both monomers and the combination. Western Blot implied that the combination regulated p53/MDM2 to a better healthy state. Furthermore, 3-1 and DMXAA arrested more cells on G2/M phase; while the combination arrested more cells on S phase. All the evidences support that the 3-1/DMXAA combination is a better anti-cancer therapy.