* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium methylate In methanol at 20℃; for 2 h;
3) 1 g of sodium methoxide (50percent content) in methanol was added to the filtrate, and the mixture was stirred at room temperature for 2 hours. Acidic cation exchange resin (732) was to adjust the pH to 7, filtered and the filtrate was removed. The filtrate was added with activated carbon (2percent) and decolorized at 70 ° C for 1 hour, filtererd, the filtrate was concentrated under reduced pressure and dissolved in 15 ml of water. The mixture was extracted 4 times with ethyl acetate (10 ml / time), the organic phase was separated. The water phase was combined, the aqueous phase was concentrated to half volume at 60 ° C under reduced pressure, extracted 4 times with n-butanol (10ml / time), the aqueous phase was separated, and the organic phases were combined. The organic phase was rotated under reduced pressure to spin-out n-butanol to give a concentrate. 4) The concentrate was recrystallized from acetone: n-butanol = 3:1 to obtain 2.30 g of salidroside, the yield is 89.8percent, purity 98percent.
General procedure: Glycoside 21a–c, 22, 23 and 25–30 was dissolved in dry MeOH (9 mL), cooled to 4 °C and 0.5 M MeONa (1 mL) was added dropwise. The mixture was stirred at 4 °C until TLC (EtOAc/MeOH 6:1) showed that the reaction is complete. The pH of the mixture was brought pH 5 using Amberlite IR 120 (H+ form). The resin was filtered off, the filtrate concentrated and the residue was subjected to column chromatography (EtOAc/MeOH 1:06:1).
86.5%
With strongly acidic cation exchange resin 717 In ethanol at 70℃;
2-(4-acetoxyphenyl)ethyl(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside 30 g was added 500 mL round bottom flask 95percent ethanol 717 strong acidic cationic resin 20g, 70 reflux overnight, TLC tracking to complete reaction, cooling to room temperature, the cationic resin recovery, ethanol and water were distilled off under reduced pressure, 100 ml of ethyl acetate was added, and the mixture was refluxed for 1 hour and then slowly cooled to room temperature, precipitation of white solid, filter, 40-60 dryness 10-12 hours to give salidroside, purity 98.2percent, yield 86.5percent.
Reference:
[1] Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 4, p. 581 - 586
[2] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 524 - 530
[3] Patent: CN106674300, 2017, A, . Location in patent: Paragraph 0071-0072
3
[ 183209-56-5 ]
[ 10338-51-9 ]
Yield
Reaction Conditions
Operation in experiment
93%
With 5%-palladium/activated carbon; hydrogen In methanol at 20℃; Darkness; Green chemistry
1.1 g (2.8 mmol) of 1-O-(4-benzyloxy)-phenylethyl yl -β-D- glucopyranoside and 5percent Pd / C 0.1 g of catalyst, and then repeatedly evacuated air charge of hydrogengas 3-5 times, and 20 mL of anhydrous methanol, protected from light, stirred at room temperature under a hydrogen atmosphere overnight.Filtration, concentration to dryness under reduced pressure,and recrystallized from ethanol to give 1-(4-hydroxy)-phenethyl-β-D-s-glucopyranoside as a white powder, which is aweight of 0.78 g. The yield was 93percent.
Reference:
[1] Patent: CN107880085, 2018, A, . Location in patent: Paragraph 0039
[2] Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 12, p. 1627 - 1629
4
[ 133-99-3 ]
[ 501-94-0 ]
[ 10338-51-9 ]
Yield
Reaction Conditions
Operation in experiment
6.7%
With β-glucosidase from Aspergillus niger In water at 37℃; for 3 h; Enzymatic reaction
Reaction mixture (100 mL) comprising of 2.0725 g (1.5 mmol) tyrosol, 15.4 g cellobiose and Novozyme 188 (735 U of β-glucosidase) in distilled water was incubated at 37 °C. The reaction was stopped after 3 h by boiling in water bath for 5 min, centrifuged for 10 min at 4500 rpm and filtered through 0.22 m filter (25 mm diameter). The filtrate was applied on column of Sephadex LH-20 (75 cm long, 3.2 mm i.d.) equilibrated and eluted with distilled water. Tyrosol was regenerated by gradient of ethanol. The process of purification was monitored by TLC. Fractions containing salidroside were collected and concentrated in vacuo. To remove coloured substances originating from the enzyme, the material was further subjected to flash chromatography with gradient of methanol in chloroform. Fractions containing pure salidroside were concentrated and crystallised from mixture of methanol and chloroform (1:5, v/v).
Reference:
[1] Letters in Organic Chemistry, 2009, vol. 6, # 2, p. 115 - 119
[2] Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 113, p. 23 - 28
With β-glycosidase from black plum seeds; 1-octyl-3-methylimidazolium hexafluorophosphate In 1,4-dioxane; aq. phosphate buffer at 50℃; for 72 h; Enzymatic reaction
General procedure: The different seed meals were prepared as described by Yuet al. [10]. The reaction was performed in a 10 ml Erlenmeyershaking flask capped with a septum containing 1.6 ml dioxane, 0.4 ml phosphate buffer (pH 6.8, 100 mmol/L), 0.5 mmolD-glucose, 5 mmol tyrosol, and different fruit seed meal at 50°C and 200 r/min. Aliquots were withdrawn at specified timeintervals from the reaction mixture, and then diluted 50 timeswith the corresponding mobile phase prior to HPLC analysis.One unit of -glycosidase activity (U) was defined as theamount of enzyme required to produce 1 μmol salidroside inthe first hour under the above conditions. The specific activitiesof the black plum seed meal, apple seed meal, peach seed meal,bitter almond seed meal, and prune seed meal were 27.6, 23.4,25.9, 13.5, and 19.7 U/g.
Reference:
[1] Chinese Journal of Catalysis, 2012, vol. 33, # 7-8, p. 1161 - 1165
[2] Journal of Molecular Catalysis B: Enzymatic, 2012, vol. 74, # 1-2, p. 24 - 28
With sodium methylate; In methanol; at 20.0℃; for 2.0h;
3) 1 g of sodium methoxide (50% content) in methanol was added to the filtrate, and the mixture was stirred at room temperature for 2 hours. Acidic cation exchange resin (732) was to adjust the pH to 7, filtered and the filtrate was removed. The filtrate was added with activated carbon (2%) and decolorized at 70 C for 1 hour, filtererd, the filtrate was concentrated under reduced pressure and dissolved in 15 ml of water. The mixture was extracted 4 times with ethyl acetate (10 ml / time), the organic phase was separated. The water phase was combined, the aqueous phase was concentrated to half volume at 60 C under reduced pressure, extracted 4 times with n-butanol (10ml / time), the aqueous phase was separated, and the organic phases were combined. The organic phase was rotated under reduced pressure to spin-out n-butanol to give a concentrate. 4) The concentrate was recrystallized from acetone: n-butanol = 3:1 to obtain 2.30 g of salidroside, the yield is 89.8%, purity 98%.
General procedure: Glycoside 21a-c, 22, 23 and 25-30 was dissolved in dry MeOH (9 mL), cooled to 4 C and 0.5 M MeONa (1 mL) was added dropwise. The mixture was stirred at 4 C until TLC (EtOAc/MeOH 6:1) showed that the reaction is complete. The pH of the mixture was brought pH 5 using Amberlite IR 120 (H+ form). The resin was filtered off, the filtrate concentrated and the residue was subjected to column chromatography (EtOAc/MeOH 1:06:1).
86.5%
With strongly acidic cation exchange resin 717; In ethanol; at 70.0℃;
2-(4-acetoxyphenyl)ethyl(2,3,4,6-O-tetraacetyl)-beta-D-glucopyranoside 30 g was added 500 mL round bottom flask 95% ethanol 717 strong acidic cationic resin 20g, 70 reflux overnight, TLC tracking to complete reaction, cooling to room temperature, the cationic resin recovery, ethanol and water were distilled off under reduced pressure, 100 ml of ethyl acetate was added, and the mixture was refluxed for 1 hour and then slowly cooled to room temperature, precipitation of white solid, filter, 40-60 dryness 10-12 hours to give salidroside, purity 98.2%, yield 86.5%.
With beta-glucosidase from Aspergillus niger; In water; at 37.0℃; for 3.0h;Enzymatic reaction;
Reaction mixture (100 mL) comprising of 2.0725 g (1.5 mmol) tyrosol, 15.4 g cellobiose and Novozyme 188 (735 U of beta-glucosidase) in distilled water was incubated at 37 C. The reaction was stopped after 3 h by boiling in water bath for 5 min, centrifuged for 10 min at 4500 rpm and filtered through 0.22 m filter (25 mm diameter). The filtrate was applied on column of Sephadex LH-20 (75 cm long, 3.2 mm i.d.) equilibrated and eluted with distilled water. Tyrosol was regenerated by gradient of ethanol. The process of purification was monitored by TLC. Fractions containing salidroside were collected and concentrated in vacuo. To remove coloured substances originating from the enzyme, the material was further subjected to flash chromatography with gradient of methanol in chloroform. Fractions containing pure salidroside were concentrated and crystallised from mixture of methanol and chloroform (1:5, v/v).
With 5%-palladium/activated carbon; hydrogen; In methanol; at 20.0℃;Darkness; Green chemistry;
1.1 g (2.8 mmol) of 1-O-(4-benzyloxy)-phenylethyl yl -beta-D- glucopyranoside and 5% Pd / C 0.1 g of catalyst, and then repeatedly evacuated air charge of hydrogengas 3-5 times, and 20 mL of anhydrous methanol, protected from light, stirred at room temperature under a hydrogen atmosphere overnight.Filtration, concentration to dryness under reduced pressure,and recrystallized from ethanol to give 1-(4-hydroxy)-phenethyl-beta-D-s-glucopyranoside as a white powder, which is aweight of 0.78 g. The yield was 93%.
With beta-glycosidase from black plum seeds; 1-octyl-3-methylimidazolium hexafluorophosphate; In 1,4-dioxane; aq. phosphate buffer; at 50.0℃; for 72.0h;pH 5.9;Enzymatic reaction;Kinetics;
General procedure: The different seed meals were prepared as described by Yuet al. [10]. The reaction was performed in a 10 ml Erlenmeyershaking flask capped with a septum containing 1.6 ml dioxane, 0.4 ml phosphate buffer (pH 6.8, 100 mmol/L), 0.5 mmolD-glucose, 5 mmol tyrosol, and different fruit seed meal at 50C and 200 r/min. Aliquots were withdrawn at specified timeintervals from the reaction mixture, and then diluted 50 timeswith the corresponding mobile phase prior to HPLC analysis.One unit of -glycosidase activity (U) was defined as theamount of enzyme required to produce 1 mumol salidroside inthe first hour under the above conditions. The specific activitiesof the black plum seed meal, apple seed meal, peach seed meal,bitter almond seed meal, and prune seed meal were 27.6, 23.4,25.9, 13.5, and 19.7 U/g.
General procedure: Each glycoside (1 mg) was dissolved in 2% NaOMe/MeOH (1 ml) at room temperature. After 1 h, the reaction mixture was neutralized by passing each through an ion-exchange resion (Amberlite IRA 400, H+ form) column. These were then heated in 1 M HCl (2 ml) at 90 C for 3 h. After cooling, each reaction mixture was neutralized by individually passing each through an ion-exchange resin (Amberlite IRA 400, OH- form) column. Each filtrate was thentransferred to a Sep-Pak C18 cartridge and eluted with H2O and MeOH, and the H2O eluated were individuals concentrated and the residued were treated with L-cysteine methyl ester hydrochloride (2 mg) in pyridine (0.25 ml) at 60 C for 1 h. After the reaction, the solution was treated with TMS-HT (100 ll, hexamethyldisilazane and trimethylchlorosilamine in pyridine, TOKYO KASEI Co., Tokyo, Japan) at 40 C for 10 min. The reaction mixture was then subjected to GLC analysis to identify the derivatives of D-glucose from 5, 6, 7 and 8. GLC conditions: column, ULBON HR-1, 25 m x 0.25 mm (i.d.), 0.25 lm; detector, FID; injector temperature, 250 C; detector temperature, 280 C; column temperature,250 C for 0.5 min and then 1.5 C/min up to 270 C; He carrier,24 cm/s; D-glucose tR, 6.83 min, respectively.
With hydrogenchloride; water; In methanol; at 90.0℃; for 3.0h;
General procedure: Each glycoside (1 mg) was dissolved in 2% NaOMe/MeOH (1 ml) at room temperature. After 1 h, the reaction mixture was neutralized by passing each through an ion-exchange resion (Amberlite IRA 400, H+ form) column. These were then heated in 1 M HCl (2 ml) at 90 C for 3 h. After cooling, each reaction mixture was neutralized by individually passing each through an ion-exchange resin (Amberlite IRA 400, OH- form) column. Each filtrate was thentransferred to a Sep-Pak C18 cartridge and eluted with H2O and MeOH, and the H2O eluated were individuals concentrated and the residued were treated with L-cysteine methyl ester hydrochloride (2 mg) in pyridine (0.25 ml) at 60 C for 1 h. After the reaction, the solution was treated with TMS-HT (100 ll, hexamethyldisilazane and trimethylchlorosilamine in pyridine, TOKYO KASEI Co., Tokyo, Japan) at 40 C for 10 min. The reaction mixture was then subjected to GLC analysis to identify the derivatives of D-glucose from 5, 6, 7 and 8. GLC conditions: column, ULBON HR-1, 25 m x 0.25 mm (i.d.), 0.25 lm; detector, FID; injector temperature, 250 C; detector temperature, 280 C; column temperature,250 C for 0.5 min and then 1.5 C/min up to 270 C; He carrier,24 cm/s; D-glucose tR, 6.83 min, respectively.
With sodium hydroxide; In methanol; at 20.0℃; for 5.0h;
(3) synthesis of salidroside (shows compound of formula I) To a 250 ml three-neck bottle 18g adding intermediate IV, methanol 120 ml, sodium hydroxide 3.3g, room temperature reaction 5h, Ph=7 regulating methanol solution of hydrogen chloride, filtering, 45 C decompression concentrated, recrystallized with ethanol, the white solid obtained 6.3g, yield 84%.
With potassium tert-butylate; In ethanol; at 20.0℃; for 5.0h;
(3) synthesis of salidroside (shows compound of formula I) To a 250 ml three-neck bottle IV16.6g adding intermediate, ethanol 120 ml, tert-butanol potassium 4.5g, room temperature reaction 5h, hydrogen chloride ethanol solution accent neutral, filtering, 45 C decompression concentrated, recrystallized with ethanol, the white solid obtained 6.7g, yield 89.3%.
With sodium ethanolate; In ethanol; at 20.0℃; for 5.0h;
(3) synthesis of salidroside (shows compound of formula I) To a 250 ml three-neck bottle IV16.6g adding intermediate, ethanol 120 ml, sodium ethoxide 4.8g, room temperature reaction 5h, hydrogen chloride ethanol solution accent neutral, filtering, 45 C decompression concentrated, recrystallized with ethanol, the white solid obtained 6.1g, yield 81.3%.
With potassium hydroxide; In methanol; at 20.0℃; for 5.0h;
(3) synthesis of salidroside (shows compound of formula I) To a 250 ml three-neck bottle IV20g adding intermediate, methanol 120 ml, potassium hydroxide 3.5g, room temperature reaction 5h, Ph=7 regulating methanol solution of hydrogen chloride, filtering, 45 C decompression concentrated, recrystallized with ethanol, the white solid obtained 6.3g, yield 84%.
With potassium ethoxide; In ethanol; at 20.0℃; for 5.0h;
(3) synthesis of salidroside (shows compound of formula I) To a 250 ml three-neck bottle IV17.1g adding intermediate, ethanol 120 ml, ethanol potassium 3.5g, room temperature reaction 5h, Ph=7 regulating methanol solution of hydrogen chloride, filtering, 45 C decompression concentrated, recrystallized with ethanol, the white solid obtained 6.5g, yield 86.7%.
With sodium methylate; In methanol; at 20.0℃; for 5.0h;
(3) synthesis of salidroside (shows compound of formula I) Flask to 250ml three intermediate IV 16. 3g, 120ml of methanol, sodium methoxide 2.5g, 5h room temperature, a solution of hydrogen chloride in methanol adjusted to pH 7 and filtered, 45 C and concentrated under reduced pressure, and recrystallized from ethanol to give a white solid 6. 5g, yield 86.7%
2-(4-hydroxyphenyl)-ethyl-(6-O-caffeoyl)-β-D-glucopyranoside[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
With Lipozyme TL IM; In tert-butyl alcohol; at 40.0℃; for 384.0h;Molecular sieve; Enzymatic reaction;
General procedure: The preparative reaction was performed in 10 mL DURAN flasks with a sealing lid on a vibrating shaker set up to 300 rpm in thermostat at constant temperature 40 C. The reaction mixture comprised 1 mmol of either methyl beta-D-glucopyranoside (194 mg) or arbutin (272 mg) or <strong>[10338-51-9]salidroside</strong> (300 mg) together with 1.5 mmol (309 mg) of vinyl caffeate, 0.4 g of activated molecular sieves 4A and 0.4 g of Lipozyme TL IM in 5 mL of tert-butanol. After the conversion became constant (monitored by HPLC), which means 17, 12 and 16 days for caffeoylation of 1, 5 and 6, respectively, the reaction mixture was filtered and solid parts including the enzyme were washed with acetonitrile. Activated charcoal was added and the suspension was briefly boiled. The mixture was filtered again and solvents were removed by evaporation. The residue was purified by chromatography on the column of silica-gel eluted with ethyl acetate. Fractions comprising the pure product were collected and the solvent was removed by evaporation. The honey-like residues was precipitated from toluene and separated by filtration under argon.
p-benzoyloxyphenethyl β-D-glucopyranoside[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
40%
With tetrabutylammomium bromide; sodium carbonate; In water; ethyl acetate; at 5.0℃;
3 g (0.01 mol) of <strong>[10338-51-9]salidroside</strong>, 1.06 g (0.01 mol) of sodium carbonate, 0.05 g of tetrabutylammonium bromide, and 10 ml of water were placed in a 50 ml three-necked flask.Ice bath, stir until the solid is completely dissolved, and the temperature of the system drops below 5 C.1.3 ml (0.01 mol) of benzoyl chloride was dissolved in 10 ml of ethyl acetate and added to the system.TLC (CHCl3:CH3OH = 4: 1) The reaction was monitored and the reaction was stopped until the starting point disappeared.The layers were separated and the aqueous extracted with EtOAc EtOAc EtOAc EtOAcThe organic phase was combined, dried over anhydrous sodiumUsing silica as the stationary phase, (CHCl3-CH3OH) was the eluent and was subjected to a gradient elution using a rapid preparative chromatography (model: Biotage isolera one) with an elution gradient of linearly increasing the methanol concentration from 0% to 20% in 3 column volumes.After the product peaked, the methanol concentration was kept constant, and the eluate at this time was collected.The <strong>[10338-51-9]salidroside</strong> derivative p-benzoyloxyphenethyl-beta-D-glucopyranoside 1.6g was obtained in a yield of 40%, and the purity was 97% by HPLC.The mass spectrometry,1H NMR and13C NMR data are shown in Figures 1-3.
1-[2-(4-benzoyloxyphenyl)ethyl]-2,3,4,6-O-tetraacetyl-β-D-glucopyranoside[ No CAS ]
[ 10338-51-9 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide; In methanol; at 20.0℃; for 2.0h;
saturated sodium hydroxide methanol solution,Dilute with methanol to adjust the pH to 11-12.The above product (10 g, 17.4 mmol) was added to the above sodium hydroxide methanol solution.Stir at room temperature for 2 h.The reaction is completed,Neutralization was carried out by adding 732 cation exchange resin to rho Eta = 7.filter,concentrate,A white solid precipitated.Recrystallization from absolute ethanol gave a white solid.
4-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)phenyl 3-(chloromethyl) benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With tetrabutylammomium bromide; sodium carbonate In water; ethyl acetate at 5℃;
4.1.2. Synthesis of phenolic hydroxyl-modified derivatives ofsalidroside
General procedure: Compounds 1a, 1b, 1c, 1d, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n, 1o, 2a, 2d, 2f, 2g and 2h were synthesized by mixing 10 mmol salidrosidewith 10 mmol sodium carbonate and 0.15 mmol tetrabutylammoniumin 10 mL water. The mixture was stirred in an ice bath untilthe solid was completely dissolved, and the temperature of mixturewas cooled at 5 C. 10 mmol of the corresponding acyl chloride (seeFig. 1), dissolved in 10 mL of ethyl acetate, was added. The mixturewas maintained at 5 C by stirring. Reactions were monitored bythin-layer chromatography (CHCl3:CH3OH 3:1) and spots werevisualized under the UV light (l 254 nm). The reaction wasstopped when the starting material was completely consumed. Thewater layerwas extracted with ethyl acetate (3 5mLwashes). Theethyl acetate layer was separated and washed with brine, driedover anhydrous Na2SO4 and evaporated under reduced pressure togive a residue which was then purified by flash column chromatographyon silica gel (the ratio of eluent CH2Cl2: CH3OH from 0:1 to1:3).
4-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)phenyl 4-(chloromethyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With tetrabutylammomium bromide; sodium carbonate In water; ethyl acetate at 5℃;
4.1.2. Synthesis of phenolic hydroxyl-modified derivatives ofsalidroside
General procedure: Compounds 1a, 1b, 1c, 1d, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n, 1o, 2a, 2d, 2f, 2g and 2h were synthesized by mixing 10 mmol salidrosidewith 10 mmol sodium carbonate and 0.15 mmol tetrabutylammoniumin 10 mL water. The mixture was stirred in an ice bath untilthe solid was completely dissolved, and the temperature of mixturewas cooled at 5 C. 10 mmol of the corresponding acyl chloride (seeFig. 1), dissolved in 10 mL of ethyl acetate, was added. The mixturewas maintained at 5 C by stirring. Reactions were monitored bythin-layer chromatography (CHCl3:CH3OH 3:1) and spots werevisualized under the UV light (l 254 nm). The reaction wasstopped when the starting material was completely consumed. Thewater layerwas extracted with ethyl acetate (3 5mLwashes). Theethyl acetate layer was separated and washed with brine, driedover anhydrous Na2SO4 and evaporated under reduced pressure togive a residue which was then purified by flash column chromatographyon silica gel (the ratio of eluent CH2Cl2: CH3OH from 0:1 to1:3).
4-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)phenyl 3,4-dichlorobenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
52%
With tetrabutylammomium bromide; sodium carbonate In water; ethyl acetate at 5℃;
4.1.2. Synthesis of phenolic hydroxyl-modified derivatives ofsalidroside
General procedure: Compounds 1a, 1b, 1c, 1d, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n, 1o, 2a, 2d, 2f, 2g and 2h were synthesized by mixing 10 mmol salidrosidewith 10 mmol sodium carbonate and 0.15 mmol tetrabutylammoniumin 10 mL water. The mixture was stirred in an ice bath untilthe solid was completely dissolved, and the temperature of mixturewas cooled at 5 C. 10 mmol of the corresponding acyl chloride (seeFig. 1), dissolved in 10 mL of ethyl acetate, was added. The mixturewas maintained at 5 C by stirring. Reactions were monitored bythin-layer chromatography (CHCl3:CH3OH 3:1) and spots werevisualized under the UV light (l 254 nm). The reaction wasstopped when the starting material was completely consumed. Thewater layerwas extracted with ethyl acetate (3 5mLwashes). Theethyl acetate layer was separated and washed with brine, driedover anhydrous Na2SO4 and evaporated under reduced pressure togive a residue which was then purified by flash column chromatographyon silica gel (the ratio of eluent CH2Cl2: CH3OH from 0:1 to1:3).
4-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)phenyl 2,3-dichlorobenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With tetrabutylammomium bromide; sodium carbonate In water; ethyl acetate at 5℃;
4.1.2. Synthesis of phenolic hydroxyl-modified derivatives ofsalidroside
General procedure: Compounds 1a, 1b, 1c, 1d, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n, 1o, 2a, 2d, 2f, 2g and 2h were synthesized by mixing 10 mmol salidrosidewith 10 mmol sodium carbonate and 0.15 mmol tetrabutylammoniumin 10 mL water. The mixture was stirred in an ice bath untilthe solid was completely dissolved, and the temperature of mixturewas cooled at 5 C. 10 mmol of the corresponding acyl chloride (seeFig. 1), dissolved in 10 mL of ethyl acetate, was added. The mixturewas maintained at 5 C by stirring. Reactions were monitored bythin-layer chromatography (CHCl3:CH3OH 3:1) and spots werevisualized under the UV light (l 254 nm). The reaction wasstopped when the starting material was completely consumed. Thewater layerwas extracted with ethyl acetate (3 5mLwashes). Theethyl acetate layer was separated and washed with brine, driedover anhydrous Na2SO4 and evaporated under reduced pressure togive a residue which was then purified by flash column chromatographyon silica gel (the ratio of eluent CH2Cl2: CH3OH from 0:1 to1:3).
4-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)phenyl heptanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With tetrabutylammomium bromide; sodium carbonate In water; ethyl acetate at 5℃;
4.1.2. Synthesis of phenolic hydroxyl-modified derivatives ofsalidroside
General procedure: Compounds 1a, 1b, 1c, 1d, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n, 1o, 2a, 2d, 2f, 2g and 2h were synthesized by mixing 10 mmol salidrosidewith 10 mmol sodium carbonate and 0.15 mmol tetrabutylammoniumin 10 mL water. The mixture was stirred in an ice bath untilthe solid was completely dissolved, and the temperature of mixturewas cooled at 5 C. 10 mmol of the corresponding acyl chloride (seeFig. 1), dissolved in 10 mL of ethyl acetate, was added. The mixturewas maintained at 5 C by stirring. Reactions were monitored bythin-layer chromatography (CHCl3:CH3OH 3:1) and spots werevisualized under the UV light (l 254 nm). The reaction wasstopped when the starting material was completely consumed. Thewater layerwas extracted with ethyl acetate (3 5mLwashes). Theethyl acetate layer was separated and washed with brine, driedover anhydrous Na2SO4 and evaporated under reduced pressure togive a residue which was then purified by flash column chromatographyon silica gel (the ratio of eluent CH2Cl2: CH3OH from 0:1 to1:3).