6683-48-3

Usage

Chemical Properties

White Solid

Uses

Targretin analog, has been shown to induce apoptosis in certain leukemia cell lines.

InChI:InChI=1/C15H22/c1-11-6-7-12-13(10-11)15(4,5)9-8-14(12,2)3/h6-7,10H,8-9H2,1-5H3

Synthetic route

2,5-dichloro-2,5-dimethyl hexane (6223-78-5) + toluene (108-88-3) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
With aluminium trichloride for 12h; Heating;	99%
With aluminium trichloride In dichloromethane at 20℃; Friedel-Crafts alkylation;	99%
With aluminium trichloride In dichloromethane Friedel-Crafts alkylation; Heating;	97%

2,5-dichloro-2,5-dimethyl hexane (6223-78-5) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
With aluminum (III) chloride In toluene for 0.416667h;	97%

1,1,4,4,6-pentamethyl-1,4-dihydronaphthalene (167958-79-4) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate for 1h;	80%

toluene (108-88-3) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Stage #1: 2,5-dimethyl-2,5-hexanediol With hydrogenchloride In water at 20℃; for 1h; Stage #2: toluene With aluminum (III) chloride In dichloromethane at 20℃; for 3h;	76%

5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalene-1-carbaldehyde (127459-66-9) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
With Wilkinson's catalyst In toluene Heating;

2,5-dimethyl-2,5-hexanediol (110-03-2) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl conc. / 3 h / 20 °C 2: 99 percent / AlCl3 / CH2Cl2 / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 56 percent / HCl gas / ethanol 2: 91 percent / AlCl3 / CH2Cl2 / 1.) RT, 30 min, 2.) reflux, 15 min View Scheme
Multi-step reaction with 2 steps 1: conc. HCl, HCl gas / 0.25 h / 0 °C 2: 80.4 percent / AlCl3 / 1 h / 0 °C View Scheme

1,1,4,4,7-pentamethyl-2-oxo-1,2,3,4-tetrahydronaphthalene (29020-85-7) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 87 percent / LiAlH4 / diethyl ether / 1 h / Heating 2: 79 percent / POCl3, pyridine / 100 °C 3: 80 percent / H2 / 10percent Pd/C / ethyl acetate / 1 h View Scheme

2,2,5,5-tetramethyltetrahydro-3-oxofuran (5455-94-7) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 45 percent / AlCl3 / 2 h / 0 - 20 °C 2: 87 percent / LiAlH4 / diethyl ether / 1 h / Heating 3: 79 percent / POCl3, pyridine / 100 °C 4: 80 percent / H2 / 10percent Pd/C / ethyl acetate / 1 h View Scheme

toluene (108-88-3) + (+-)-o-toluenesulfinic acid-chloride → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 45 percent / AlCl3 / 2 h / 0 - 20 °C 2: 87 percent / LiAlH4 / diethyl ether / 1 h / Heating 3: 79 percent / POCl3, pyridine / 100 °C 4: 80 percent / H2 / 10percent Pd/C / ethyl acetate / 1 h View Scheme

1,1,4,4,7-pentamethyl-2-hydroxy-1,2,3,4-tetrahydronaphthalene (167958-78-3) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 79 percent / POCl3, pyridine / 100 °C 2: 80 percent / H2 / 10percent Pd/C / ethyl acetate / 1 h View Scheme

1,2,3,4-tetrahydro-1,1,4,4,5,7-hexamethylnaphthalene (94374-39-7) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NBS, 2.) 1-methylpyrrolidin-2-one, 3.) PCC / 1.) CCl4, 77 deg C, 45 min, 2.) H2O, 100 h, 1h, 3.) CH2Cl2, 20 deg C, 2 h 2: 3)3> / toluene / Heating View Scheme

m-xylene (108-38-3) + benzene; toluene → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) H2SO4, 2.) Mg, 4.) H2SO4 / 1.) 20 deg C, 3 h, 2.) THF, 75 deg C, 30 min, 3.) THF, reflux, 30 min, 4.) petroleum ether, 5 - 10 deg C, 30 min 2: 1.) NBS, 2.) 1-methylpyrrolidin-2-one, 3.) PCC / 1.) CCl4, 77 deg C, 45 min, 2.) H2O, 100 h, 1h, 3.) CH2Cl2, 20 deg C, 2 h 3: 3)3> / toluene / Heating View Scheme

2,5-dichloro-2,5-dimethyl hexane (6223-78-5) + 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran (96042-30-7) → 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3)

Conditions	Yield
With hydrogenchloride; AlCl3 In toluene

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + acetyl chloride (75-36-5) → 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalenyl)ethanone (17610-24-1)

Conditions	Yield
With aluminium trichloride In 1,2-dichloro-ethane for 1h; Ambient temperature;	99%
aluminium trichloride In 1,2-dichloro-ethane	99%
With aluminum (III) chloride In dichloromethane for 5h; Inert atmosphere; Reflux;	96%

methyl 5-(chloromethyl)-2-furoate (2144-37-8) + Methyl 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl) methyl]-2-furoate + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)methyl]-N'-(2,4,6-trimethoxybenzyl)-2-furohydrazide (637012-34-1) + 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)methyl]-2-furoic acid (263854-27-9)

Conditions	Yield
With sodium hydroxide; aluminium trichloride In methanol; dichloromethane; water; ethyl acetate	A 99% B n/a

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + 3-(methoxycarbonyl)benzoyl chloride (3441-03-0) → methyl 3-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>benzoate

Conditions	Yield
With aluminum (III) chloride Friedel Crafts Acylation;	98%
With aluminium trichloride In dichloromethane for 0.166667h; Ambient temperature;	80%
With aluminum (III) chloride In dichloromethane at 20℃; Friedel Crafts acylation; Reflux;	2.21 g

Monomethyl terephthalate (1679-64-7) + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → methyl 4-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>benzoate (153559-45-6)

Conditions	Yield
With aluminum (III) chloride; thionyl chloride In dichloromethane at 20℃; for 4h; Temperature; Solvent; Reflux;	95.3%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + 4-methoxy-benzoyl chloride (100-07-2) → (4-methoxy-phenyl)-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-methanone (544708-96-5)

Conditions	Yield
With aluminum (III) chloride In dichloromethane	95%
With aluminium trichloride Friedel-Crafts acylation;	70%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + phthalic monoacid monomethyl ester chloride (4397-55-1) → methyl 2-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>benzoate

Conditions	Yield
With aluminium trichloride In dichloromethane for 0.166667h; Ambient temperature;	91%

4-chlorosulfonylbenzoyl chloride (7516-60-1) + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzene-1-sulfonyl chloride

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 55℃; for 0.25h; Friedel-Crafts Acylation;	86%
With aluminum (III) chloride In dichloromethane at 55℃; for 0.25h;	2.3592 g

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + potassium p-carboxybenzenesulfonate (5399-63-3) → 4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzene-1-sulfonyl chloride

Conditions	Yield
Stage #1: potassium p-carboxybenzenesulfonate With thionyl chloride; N,N-dimethyl-formamide at 85℃; for 1.66667h; Stage #2: 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene With aluminum (III) chloride In dichloromethane at 55℃; for 0.25h;	86%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 2-bromo-3-methyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (119999-22-3)

Conditions	Yield
With aluminium trichloride; bromine In dichloromethane	85%
With bromine In tetrachloromethane for 0.25h; Ambient temperature;	80%
With bromine In chloroform at 20℃; for 0.5h;	60%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + 4-Methoxycarbonylbenzoyl chloride (7377-26-6) → methyl 4-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>benzoate (153559-45-6)

Conditions	Yield
With aluminum (III) chloride Friedel Crafts Acylation;	82%
With iron(III) chloride In 1,2-dichloro-ethane at 75℃; for 16h; Friedel-Crafts acylation;	81%
With aluminium trichloride In dichloromethane for 0.25h; Heating;	72%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-carboxaldehyde (92654-79-0)

Conditions	Yield
With ammonium cerium(IV) nitrate; acetic acid In water at 100℃; for 1h;	78%
With ammonium cerium(IV) nitrate In acetic acid at 20℃; for 1h;	78%
With ammonium cerium (IV) nitrate; acetic acid at 100℃; for 1h;	77%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-carboxaldehyde (92654-79-0) + 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-carboxylic acid (103031-30-7)

Conditions	Yield
With ammonium cerium(IV) nitrate; acetic acid at 100℃; for 0.25h;	A 78% B 14%
With ammonium cerium(IV) nitrate; acetic acid at 100℃; for 0.25h;	A 78% B 78%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → (5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-bromomethane (119435-90-4)

Conditions	Yield
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 2.5h; Heating / reflux;	72.5%
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In chloroform

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 1,1,4,4,6-pentamethyl-7-nitro-1,2,3,4-tetrahydronaphthalene (116233-16-0)

Conditions	Yield
With nitric acid; acetic anhydride	72%
With sulfuric acid; nitric acid at 20℃; for 4h;	62.1%
With sulfuric acid; nitric acid at -10℃;	50%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + 4-iodobenzoic acid chloride (1711-02-0) → 2-(4-iodophenyl)-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-methanone (926038-65-5)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 0℃; for 0.166667h;	71%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + methyl 2-acetoxy-4-(chlorocarbonyl)benzoate → methyl 2-hydroxy-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 55℃; for 0.25h;	70%

methyl 5-(chloromethyl)-2-furoate (2144-37-8) + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → methyl 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-methyl]-2-furoate (263854-26-8)

Conditions	Yield
With aluminium trichloride In dichloromethane Friedel-Crafts alkylation; Heating;	68%
aluminum (III) chloride In dichloromethane for 2h; Heating / reflux;	46%
With aluminum (III) chloride In dichloromethane for 2h; Friedel Crafts Acylation; Heating / reflux;	46%

methyl 2-(chlorocarbonyl)pyrimidine-5-carboxylate (1427690-41-2) + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → methyl 2-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl]pyrimidine-5-carboxylate (1427690-40-1)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 20℃; Reflux;	68%
With aluminum (III) chloride In dichloromethane at 20℃; for 0.333333h; Friedel-Crafts Acylation; Reflux;	1.677 g

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-carboxylic acid (103031-30-7)

Conditions	Yield
With potassium permanganate; sodium hydroxide In water; chlorobenzene at 100℃; for 16h;	63.3%
Stage #1: 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene With potassium permanganate; sodium hydroxide In pyridine; water at 95℃; for 16h; Stage #2: With hydrogenchloride In pyridine; water at 1℃; pH=1;	57%
With potassium permanganate Alkaline conditions;	57%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + trifluoromethyl 4-fluorobenzene-1-sulfonate → 1,1,4,4-tetramethyl-6-((trifluoromethoxy)methyl)-1,2,3,4-tetrahydronaphthalene

Conditions

Yield

Stage #1: 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene With 1,10-phenanthroline-5,6-dione; bathophenanthroline; silver trifluoromethanesulfonate; 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(trifluoromethanesulfonate); cesium fluoride at 20℃; for 0.0833333h; Glovebox; Sealed tube; Inert atmosphere; Stage #2: trifluoromethyl 4-fluorobenzene-1-sulfonate at 25℃; for 15h; Glovebox; Sealed tube; Inert atmosphere;

59%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → 1,2,3,4-tetrahydro-1,1,4,4,6-pentamethyl-5,7-dinitronaphthalene (92649-05-3)

Conditions	Yield
With sulfuric acid; nitric acid In 1,2-dichloro-ethane at 0℃; for 2h;	57%
With sulfuric acid; nitric acid

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + 6-chlorocarbonyl-nicotinic acid methyl ester (169124-35-0) → methyl 6-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>nicotinate (153559-92-3)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 20℃; Reflux;	54%
With aluminium trichloride In dichloromethane for 0.166667h; Ambient temperature;	50%
With aluminium trichloride In nitromethane; dichloromethane at 15 - 30℃; for 24h; Friedel-Crafts acylation;
With aluminum (III) chloride In dichloromethane at 20℃; for 0.333333h; Friedel-Crafts Acylation; Reflux;	1.3 g

5-carbethoxythiophene-2-carbonyl chloride (156910-44-0) + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → ethyl 5-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>thiophene-2-carboxylate (156910-45-1)

Conditions	Yield
With aluminium trichloride In 1,2-dichloro-ethane for 16h; Ambient temperature;	50%

1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) + benzoyl chloride (98-88-4) → ethyl 5-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>thiophene-2-carboxylate (156910-45-1)

Conditions	Yield
aluminium trichloride In 1,2-dichloro-ethane	50%

4-(1,3,2-dioxaborinan-2-yl)benzoyl chloride (481725-56-8) + 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (6683-48-3) → C22H27BO3 (926038-69-9)

Conditions	Yield
With aluminum (III) chloride	47%

Upstream product

• 6223-78-5 2,5-dichloro-2,5-dimethyl hexane 
• 108-88-3 toluene 
• 167958-79-4 1,1,4,4,6-pentamethyl-1,4-dihydronaphthalene 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 108-38-3 m-xylene 
• 94374-39-7 1,2,3,4-tetrahydro-1,1,4,4,5,7-hexamethylnaphthalene 
• 167958-78-3 1,1,4,4,7-pentamethyl-2-hydroxy-1,2,3,4-tetrahydronaphthalene 
• 5455-94-7 2,2,5,5-tetramethyltetrahydro-3-oxofuran 
• 29020-85-7 1,1,4,4,7-pentamethyl-2-oxo-1,2,3,4-tetrahydronaphthalene 
• 110-03-2 2,5-dimethyl-2,5-hexanediol 
• 127459-66-9 5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalene-1-carbaldehyde 

Downstream Products

• 94003-21-1 1.1.4.4.6-Pentamethyl-7-propionyl-tetralin 
• 544708-96-5 (4-methoxy-phenyl)-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-methanone 
• 119999-15-4 2-(4-Bromo-phenyl)-1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-propan-1-one 
• 119999-07-4 trans-4-<2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)cyclopropyl>benzoic Acid 
• 116232-92-9 4-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)cerbamoyl>benzoic acid 
• 116263-41-3 methyl 4-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)cerbamoyl>benzoate 
• 120022-39-1 Ethyl trans-4-<2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)cyclopropyl>benzoate 
• 119999-33-6 Ethyl cis-4-<2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)cyclopropyl>benzoate 
• 119435-90-4 (5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-bromomethane 
• 637012-34-1 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)methyl]-N'-(2,4,6-trimethoxybenzyl)-2-furohydrazide 
• 263854-27-9 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)methyl]-2-furoic acid 
• 17610-24-1 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalenyl)ethanone 
• 153559-73-0 ethyl 6-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)nicotinate 
• 1347735-37-8 ethyl 6-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)nicotinate 

Relevant academic research and scientific papers

Synthetic method of retinoic acid derivative Am580

The invention discloses a synthetic method of retinoic acid derivative Am580, which comprises: stirring a solution of 2, 5-dimethyl hexane-2, 5-diol in concentrated HCl for 30 min, introducing HCl gasinto the system, carrying out a reaction for 3 h, performing stirring until the system becomes a two-phase mixture, performing cooling to a room temperature, performing filtering to obtain a light pink solid, washing the solid with water, performing recrystallizing in methanol, and performing filtering to obtain an intermediate 3 which is a white solid; dissolving 2, 5-dichloro-2, 5-dimethylhexane in an organic solvent, adding AlCl3 into the solution according to a molar ratio of the 2, 5-dichloro-2, 5-dimethylhexane to the AlCl3 of 1: 0.1-1: 0.2, performing heating to 100-120 DEG C, performing stirring for 16 hours, quenching the reaction by using 3M HCl, performing extracting by using normal hexane, and performing distilling under reduced pressure to remove the solvent to obtain a colorless oily matter intermediate 4. The method has the beneficial effects that the yield of each step is relatively high, the post-treatment is simple, and the industrial production is easier; reaction conditions and a solvent system are optimized for the Friedel-Crafts reaction and the oxidation reaction, and industrial production is better facilitated.

Development of Selective TGR5 Ligands Based on the 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene Skeleton

TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC50 value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.

Carboxylation of Aryl Triflates with CO2 Merging Palladium and Visible-Light-Photoredox Catalysts

We report herein a visible-light-promoted, highly practical carboxylation of readily accessible aryl triflates at ambient temperature and a balloon pressure of CO2 by the combined use of palladium and photoredox Ir(III) catalysts. Strikingly, the stoichiometric metallic reductant is replaced by a nonmetallic amine reductant providing an environmentally benign carboxylation process. In addition, one-pot synthesis of a carboxylic acid directly from phenol and modification of estrone and concise synthesis of pharmaceutical drugs adapalene and bexarotene have been accomplished via late-stage carboxylation reaction. Furthermore, a parallel decarboxylation-carboxylation reaction has been demonstrated in an H-type closed vessel that is an interesting concept for the strategic sector. Spectroscopic and spectroelectrochemical studies indicated electron transfer from the Ir(III)/DIPEA combination to generate aryl carboxylate and Pd(0) for catalytic turnover.

BEXAROTENE DERIVATIVES AND THEIR USE IN TREATING CANCER

This disclosure relates to compositions and methods for treating cancer. Specifically, this disclosure relates to bexarotene derivatives, methods for treating cancer, autoimmune disorders, and/or skin dermatitis, and/or methods for increasing peripheral blood counts and/or improving immune system function.

COMPOUNDS AND METHODS FOR INHIBITING CYP26 ENZYMES

Compounds described herein are inhibitors of retinoic acid inducible P450 (CYP26) enzymes, and are useful for treating diseases that are responsive to retinoids. Certain compounds have retinoid activity, are resistant to CYP26-mediated catabolism, and are used for treating diseases that are responsive to retinoids.

Synthesis of a new fluorine-18-labeled bexarotene analogue for PET imaging of retinoid X receptor

The reference standard 2-fluoro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)ben-zoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and 2-fluoro-4-methylbenzoic acid in 10 steps with 3% overall chemical yield. The precursor 2-nitro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetra-hydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and dimethyl-2-nitroterephthalate in seven steps with 2% overall chemical yield. The target tracer 2-[18F]flu-oro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from its nitro-precursor by the nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC combined with solid-phase extraction (SPE) purification in 20-30% radiochemical yield with 37-370 GBq/μmol specific activity at end of bombardment (EOB).

Synthesis of a new fluorine-18-labeled bexarotene analogue for PET imaging of retinoid X receptor

The reference standard 2-fluoro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and 2-fluoro-4-methylbenzoic acid in 10 steps with 3% overall chemical yield. The precursor 2-nitro-4-(1-(3,5,5,8,8-pentamethyl-5, 6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and dimethyl-2-nitroterephthalate in seven steps with 2% overall chemical yield. The target tracer 2-[18F]fluoro-4-(1- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from its nitro-precursor by the nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC combined with solid-phase extraction (SPE) purification in 20-30% radiochemical yield with 37-370 GBq/μmol specific activity at end of bombardment (EOB).

Cucurbituril slippage: Cations as supramolecular lubricants

The dethreading rate of a polyaminated axle flanked by two benzo-15-crown-5 stoppers from the cavity of Cucurbit[7]uril (CB[7]) was enhanced by up to 500 times in the presence of aqueous metallic and organic cations. Cations likely stabilize the highest energy transition state of the dethreading process by interacting with both crown ether and CB[7] units.

Modeling, Synthesis and Biological Evaluation of Potential RetinoidX Receptor-Selective Agonists: Novel Halogenated Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene)

The synthesis of halogenated analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), known commonly as bexarotene, and their evaluation for retinoidX receptor (RXR)-specific agonist performance is described. Compound 1 is FDA approved to treat cutaneous T-cell lymphoma (CTCL); however, bexarotene treatment can induce hypothyroidism and elevated triglyceride levels, presumably by disrupting RXR heterodimer pathways for other nuclear receptors. The novel halogenated analogues in this study were modeled and assessed for their ability to bind to RXR and stimulate RXR homodimerization in an RXRE-mediated transcriptional assay as well as an RXR mammalian-2-hybrid assay. In an array of eight novel compounds, four analogues were discovered to promote RXR-mediated transcription with EC50 values similar to that of 1 and are selective RXR agonists. Our approach also uncovered a periodic trend of increased binding and homodimerization of RXR when substituting a halogen atom for a proton ortho to the carboxylic acid on 1.

Retinoid compounds and their use

The invention relates to retinoid compounds of the formula (I): wherein V is a hydrophobic group;W is a non-polyenic linker; andX is a polar group comprising a hydrogen bond donor; or a salt thereof, and to the use of such compounds in the control of cell differentiation.