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Preparation of authentic 1,4-di-O-propanoyl derivatives of hydroquinones
General procedure: To a stirred solution of 1a (420 mg, 3.0 mmol) in dry pyridine (20 ml) was added dropwise from a syringe propanoyl chloride (564 mg, 6.3 mmol), and the mixture was stirred at 100 C for 3 days. 1-(2-Aminoethyl)piperazine (81 mg, 0.63 mmol) was added and the mixture was stirred for 30 min. Then 0.5 M HCl (60 ml) was added and the mixture was extracted with EtOAc (320 ml), the organic extracts were washed successively with 1 M NaOH (330 ml), water (30 ml), and brine (30 ml), and dried over Na2SO4. After evaporation of the solvent in vacuo, the residual oil was purified by column chromatography using hexane-EtOAc (2:1, v/v) as an elu-ent to give the dipropanoate 4a as white crystals (415 mg, 59%)
With Candida antarctica lipase B In di-isopropyl ether at 45℃; for 24h;
1: 73 %Spectr.
2: 8 %Spectr.
3: 12 %Spectr.
With lipase B from Candida antarctica, immobilized form In di-isopropyl ether at 45℃; for 24h; Enzymatic reaction; Overall yield = 93 %Spectr.; regioselective reaction;
Stage #1: benzene-1,4-diyl diacetate With aluminium trichloride; sodium chloride at 195℃; for 0.15h;
Stage #2: With hydrogenchloride; amalgamated zinc for 3h; Heating; Further stages.;
Multi-step reaction with 4 steps
1: 1.) NaH, 2.) NaI / dimethylformamide / Ambient temperature
2: (C2H5)3N / CCl4 / 4 h / Ambient temperature
3: 0.5 M aq. sodium acetate / tetrahydrofuran / 1.5 h
4: toluene / 24 h / 70 °C
Multi-step reaction with 3 steps
1: diethyl ether / anschliessendes Behandeln mit Aethylenoxid
2: KOH
3: platinum; methanol / Hydrogenation.Erwaermen des Reaktionsprodukts mit einem Kationen-Austauscher in Methanol
Multi-step reaction with 2 steps
1: KOH
2: platinum; methanol / Hydrogenation.Erwaermen des Reaktionsprodukts mit einem Kationen-Austauscher in Methanol
Multi-step reaction with 4 steps
2: diethyl ether / anschliessendes Behandeln mit Aethylenoxid
3: KOH
4: platinum; methanol / Hydrogenation.Erwaermen des Reaktionsprodukts mit einem Kationen-Austauscher in Methanol
A
2-Ethylhydroquinone (1.85 mmol) and 1-adamantanecarbonyl chloride (1.4 eq.) were suspended in CH2Cl2 (3 mL/mmol), pyridine (1 mL/mmol) was added, and the mixture stirred at r.t. for 48 h. The mixture was diluted with ethyl acetate, which was extracted once with half satd aq. NaHCO3 and brine (4:1) and twice with aq. CuSO4 (6 g CuSO4*5H2O in 100 mL; 2x). Title compound was attained upon purification by prep. TLC (2 mm silica gel, PE/ethyl acetate 3:1) with 86% yield.
With triethylsilane; trifluoroacetic acid In dichloromethane at 0 - 20℃; for 15h;
Intermediate I. XXXIII
2-Ethyl-benzene-l ,4-diol2-Ethyl-benzene-l ,4-diolTrifluoroaceticacid ( 120 ml, 1623 mmol) was added dropwise to a solution of 2-( I - Hydroxy-ethyl)-benzene- l ,4-diol (intermediate LXXXII) (25 g, 162 mmol), triethylsi lane (26 ml, 162 mmol) in 250 ml of dichloromethane at 0 °C. The reaction mixture was stirred at room temperature for 1 5 hour. Then the reaction mixture was quenched with ice-cold water and evaporated the solvent. The residue was taken in water and extarcted with ethyl acetate. The comboned organic extract was washed with water, brine, dried over anhydrous sodium sulphate and evaporated. The crude material was purified using column chromatography (si lica gel 100-200 mesh, 10:90 ethylacetate:hexane) to afford 2-Ethyl- benzene- l , 4-diol in 89 % yield.
Multi-step reaction with 2 steps
1: lipase B from Candida antarctica, immobilized form / di-isopropyl ether / 24 h / 45 °C / Enzymatic reaction
2: lipase B from Candida antarctica, immobilized form; propan-1-ol / di-isopropyl ether / 1 h / 45 °C / Enzymatic reaction
Multi-step reaction with 2 steps
1: pyridine / 72 h / 100 °C
2: lipase B from Candida antarctica, immobilized form; propan-1-ol / di-isopropyl ether / 1 h / 45 °C / Enzymatic reaction
With lipase B from Candida antarctica, immobilized form In di-isopropyl ether at 45℃; for 72h; Enzymatic reaction; regioselective reaction;
Preparation of authentic 4-O-monopropanoyl derivatives of hydroquinones
General procedure: To a solution of 1c (204 mg, 1.5 mmol) and vinyl propanoate (490 ml, 4.5 mmol) in dry diisopropyl ether (3.6 ml) was added CAL-B (300 mg), and the mixture was stirred at 45C for 3 days. TLC showed the disappearance of the parent hydroquinone in the reaction mixture. The enzyme was filtered off and the filtrate was evaporated in vacuo. From the residual oil the monopropanoate 2c was isolated as the major product by preparative TLC using hexane-EtOAc (2:1, v/v) as a developing solvent to give an oil (261 mg, 90%).
3.5. Acid hydrolysis of 6-8
A solution of 6e8 (1.0 mg) in 6 N HCl was stirred at 60 C for1.5 h. After cooling, the mixtures were extracted with EtOAc. The aqueous layer was concentrated in vacuo followed by TLC examination and optical rotation measurement. The optical rotation of the glucose of 6-8 are as follows: [a]D25 45.0 (c 0.044, H2O) for 6,[a]D25 42.3 (c 0.052, H2O) for 7, and [a]D25 40.9 (c 0.044, H2O) for 8. By comparing optical rotation with D-glucose: [a]D25 42.3 (c0.106, H2O), the glucose in compounds 6-8 were determined to be D-configurations
3.5. Acid hydrolysis of 6-8
A solution of 6e8 (1.0 mg) in 6 N HCl was stirred at 60 C for1.5 h. After cooling, the mixtures were extracted with EtOAc. The aqueous layer was concentrated in vacuo followed by TLC examination and optical rotation measurement. The optical rotation of the glucose of 6-8 are as follows: [a]D25 45.0 (c 0.044, H2O) for 6,[a]D25 42.3 (c 0.052, H2O) for 7, and [a]D25 40.9 (c 0.044, H2O) for 8. By comparing optical rotation with D-glucose: [a]D25 42.3 (c0.106, H2O), the glucose in compounds 6-8 were determined to be D-configurations
3.5. Acid hydrolysis of 6-8
A solution of 6e8 (1.0 mg) in 6 N HCl was stirred at 60 C for1.5 h. After cooling, the mixtures were extracted with EtOAc. The aqueous layer was concentrated in vacuo followed by TLC examination and optical rotation measurement. The optical rotation of the glucose of 6-8 are as follows: [a]D25 45.0 (c 0.044, H2O) for 6,[a]D25 42.3 (c 0.052, H2O) for 7, and [a]D25 40.9 (c 0.044, H2O) for 8. By comparing optical rotation with D-glucose: [a]D25 42.3 (c0.106, H2O), the glucose in compounds 6-8 were determined to be D-configurations
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 7h; Inert atmosphere; Cooling with ice;
2
In a nitrogen atmosphere, 3.1 g of the compound represented by the formula (R-2-4), 11.3 g of the compound represented by the formula (R-2-3), 0.6 g of 4-dimethylaminopyridine in a reaction vessel, 100 mL of dichloromethane was added. While cooling with ice, 6.9 g of diisopropylcarbodiimide was added dropwise., Stirred at room temperature for 7 hours. The precipitate was removed by filtration, and the filtrate was washed successively with 5% hydrochloric acid, water and brine. Purification by column chromatography (alumina, dichloromethane) and recrystallization (dichloromethane/methanol) gave 10.9 g of a compound represented by the formula (R-2-5).
With D-Glucose; oxygen; quintuple recombinant E. coli cells coexpressing P450 BM3 monooxygenase F87V/L188P/I401P/R47L/Y51F and glucose dehydrogenase; NADPH In aq. phosphate buffer; dimethyl sulfoxide at 25℃; for 12h; Green chemistry; Enzymatic reaction; regioselective reaction;
With D-Glucose; oxygen; recombinant E. coli cells coexpressing P450 BM3 monooxygenase F87V and glucose dehydrogenase; NADPH In aq. phosphate buffer at 22℃; for 2h; Green chemistry; Enzymatic reaction; regioselective reaction;
With D-Glucose; oxygen; triple recombinant E. coli cells coexpressing P450 BM3 monooxygenase F87V/L188P/R47I and glucose dehydrogenase; NADPH In aq. phosphate buffer at 22℃; for 2h; Green chemistry; Enzymatic reaction; regioselective reaction;