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Chemical Structure| 57-10-3 Chemical Structure| 57-10-3
Chemical Structure| 57-10-3

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Palmitic acid, a natural product isolated and purified from the herbs of Atractylodes macrocephala Koidz., induces down-regulation of APOM expression and anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. Palmitic acid has a significant impact on proliferation and differentiation of NSCs in vitro and may be useful for elucidating the role of SFAs in regulating NSCs fate in physiological and pathological settings.Palmitic acid can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells.

Synonyms: Hexadecanoic acid; Cetylic acid; NSC 5030

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Product Details of Palmitic Acid

CAS No. :57-10-3
Formula : C16H32O2
M.W : 256.42
SMILES Code : CCCCCCCCCCCCCCCC(O)=O
Synonyms :
Hexadecanoic acid; Cetylic acid; NSC 5030
MDL No. :MFCD00002747
InChI Key :IPCSVZSSVZVIGE-UHFFFAOYSA-N
Pubchem ID :985

Safety of Palmitic Acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Application In Synthesis of Palmitic Acid

* 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.

  • Downstream synthetic route of [ 57-10-3 ]

[ 57-10-3 ] Synthesis Path-Downstream   1~32

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YieldReaction ConditionsOperation in experiment
97% With alumina methanesulfonic acid; at 120℃; for 0.333333h;Microwave irradiation; General procedure: In a typical reaction, AMA 2:3 (332 g, 0.6 mol), the corresponding carboxylicacid (1 mol), and alcohol (1.5-2 mol) were mixed in the provided reaction glass tubeequipped with a screw cap and magnetic agitation until a wet mixture was achieved.The reaction mixture was irradiated with microwaves (Anton Parr Monowave 300reactor) at 80 C for 8 min or 120 C for 20 min. On cooling, the mixture was diluted with dichloromethane (41 mL), filtered under gravity, and washed with dichloromethane;then the filtrate was washed with Na2CO3 (ss) and water. The organic layerwas dried over Na2SO4, filtered, and concentrated under reduced pressure to give theester.
95.5% With 8-hydroxyquinoline sulphate; at 85℃; for 4h; In a 100 mL three-necked flask, 0.05 mol of palmitic acid, 0.35 mol of ethanol and 0.03 mol of 8-hydroxyQuinoline bisulfate ionic liquid, to maintain the reaction temperature of about 85 , equipped with reflux condenser, stirring at constant temperature 4h. anti-At the end of this step, the unreacted excess ethanol was removed under reduced pressure, the mixture was transferred to a separatory funnel, and an appropriate amount of saturated brine was addedPolyester, shaking, to be layered, discard the lower water, keep the upper oil, repeated washing 2 to 3 times, the final oilThe product was the product palmitic acid ethyl ester in a yield of 95.5%.
84.9% With glycine ethyl ester hydrochloride; In cyclohexane; at 78℃; for 8h; Into a 500 mL three-necked flask equipped with a thermometer and a water separator, add 150 mL of absolute ethanol, 51.3 g (0.2 mol) of palmitic acid, stir and mix well, and add 50 mL of cyclohexane and 2.52 g (0.02 mol) of glycine methyl ester hydrochloride. The temperature was raised to reflux (temperature: 78 C) and the reaction was performed for 8 hours. After the temperature was lowered to room temperature, the solvent was recovered by concentration, and 50 mL of water was added to the concentrate, followed by extraction with 150 mL of ethyl acetate. The ethyl acetate layer was washed twice with 50% aqueous 5% sodium chloride, each 50 mL. The ethyl acetate layer was concentrated to obtain 55.4 g of a crude product as a final product, which was distilled under reduced pressure, and collected 171-175oC / 0.02 MPa to obtain 48.3 g of ethyl palmitate,The final product was a light yellow oily liquid, which became white crystals upon standing.The purity by gas chromatography was 98.6% and the reaction yield was 84.9%. The structure was confirmed by nuclear magnetic characterization.
91.7%Chromat. at 300℃; under 112511 Torr; for 0.233333h; An esterification reaction of a fatty acid and alcohol or a transesterification of rapeseed oil and alcohol was conducted using, as a raw material, fats and oils and alcohols shown in Table 7, under conditions of mole ratio, temperature, pressure and reaction time shown in Table 7. Since about 98.5% of rapeseed oil is composed of a tri-glyceride, the reaction from rapeseed oil can be judged to be a transesterification. The reaction product was subjected to HPLC analysis in the same manner as in Example 1, from the HPLC analysis result, conversion into a fatty acid alkyl ester from a fatty acid or rapeseed oil (=yield of alkyl ester) was obtained. The results are shown in Table 7 together with the reaction conditions. TABLE 7 Alcohol/fats and oils Temperature Pressure Reaction Example (mole ratio) Fats and oils Alcohol ( C.) (Mpa) time (min) Yield (%) Example 42/1C18-3 Methanol 300 20 8 96.2 5-1 Example 42/1C18-2 300 20 8 95.1 5-2 Example 42/1C18-1 300 20 8 95.8 5-3 Example 42/1C18-0 300 20 8 94.7 5-4 Example 42/1C16-0 300 20 8 94.0 5-5 Example 42/1 Rapeseed 300 20 15 98.0 5-6 oil Example 42/1 Rapeseed 350 43 4 98.0 5-7 oil Example 42/1C18-3 Ethanol 300 15 12 94.6 5-8 Example 42/1C18-2 300 15 14 97.4 5-9 Example 42/1C18-1 300 15 14 95.9 5-10 Example 42/1C18-0 300 15 15 91.2 5-11 Example 42/1C16-0 300 15 14 91.7 5-12 Example 42/1 Rapeseed 300 15 45 96.7 5-13 oil Example 42/1 Rapeseed 350 25 10 97.1 5-14 oil Example 42/1C18-3 1-propanol 300 10 15 97.0 5-15 Example 42/1C18-2 300 10 14 92.7 5-16 Example 42/1C18-1 300 10 14 92.3 5-17 Example 42/1C18-0 300 10 14 89.6 5-18 Example 42/1C16-0 300 10 14 90.1 5-19 Example 42/1 Rapeseed 300 10 45 96.1 5-20 oil Example 42/1 Rapeseed 350 23 14 98.8 5-21 oil Example 42/1C18-3 1-butonal 300 9 15 97.3 5-22 Example 42/1C18-2 300 9 14 92.4 5-23 Example 42/1C18-1 300 9 14 86.1 5-24 Example 42/1C18-0 300 9 14 82.5 5-25 Example 42/1C16-0 300 9 14 81.1 5-26 Example 42/1 Rapeseed 300 9 45 87.1 5-27 oil Example 42/1 Rapeseed 350 23 14 95.3 5-28 oil Example 42/1 Rapeseed 1-octanol 300 6 45 68.7 5-29 oil Example 42/1 Rapeseed 350 19 20 90.7 5-30 oil C16-0: palmitic acid, C18-0: stearic acid, C18-1: oleic acid, C18-2: linoleic acid, C18-3: linolenic acid
amberlyst-15; at 80 - 120℃; under 3620.13 Torr; for 1 - 6h;Conversion of starting material; EXAMPLE 1; Palmitic acid (90%, Sigina-Aldrichi) was combined with ethanol at a composition of 1 mole palmitic acid to 5 moles ethanol. Palmitic acid is a solid at room temperature and must be heated to about 60 C. to first melt it prior to mixing with hot ethanol, or alternatively the mixture can be combined and heated to about 50 C., at which point this amount of palmitic acid will dissolve in ethanol. The reactants were then heated and pumped through a packed bed catalytic reactor containing Amberlyst-15. The reactants were maintained at a temperature above 60 C. prior to entering the catalytic reactor. The temperature of the reactor was kept at a temperature of between 60 C. and 120 C. For each run an elevated pressure was maintained on the reactor and pre-reactor feed lines suitable to keep the ethanol and reaction by-product water in a liquid state. Run 1 used a pre-reactor temperature of 80 C. and a reactor temperature of 120 C. (reactor contained a packed bed of Amberlyst-15) and a residence time in the packed bed reactor of 2 hours. The pressure was maintained at 70 psia (the bubble point pressure of ethanol at 120 C. is 62 psia). The acid value of the product that exited the catalytic reactor was determined by ASTM method D1980-87. The acid value (AV) of the product was 10.8 (mg KOH/g sample). The original acid value of the feedstock was 115.0, demonstrating that a majority of the free fatty acid was converted to the ethyl ester product in the reactor. The AV of 10.8 is very near the reported equilibrium concentration of free fatty acid for this esterification reaction. The product was a clear liquid at room temperature. The product from the reactor contained the ethyl palmitate ester, a small amount of palmitic acid, water and excess ethanol at a concentration approximately at equilibrium. Run 2 was performed using the same palmitic acid and ethanol (1:5 mole:mole) feed and the same reactor and catalyst (Amberlyst-15) as run 1, but the residence time was 1 hour (at 120 C. and at a pressure of 70 psia). The product from run 2 had an acid value of 13.9, slightly above the equilibrium value. Run 3 was performed using the same palmitic acid and ethanol (1:5 mole:mole) feed and the same reactor and catalyst (Amberlyst-15) as run 1, but the residence time was 6 hours at 110 C. and at a pressure of 70 psia. The product from run 3 had an acid value of 16.6. Thus a large fraction of the free fatty acids were converted to alkyl ester in one pass at these conditions. Run 4 was performed using the same palmitic acid and ethanol (1:5 mole:mole) feed and the same reactor and catalyst (Amberlyst-15) as run 1, but the residence time was 4 hours (at 120 C. and at a pressure of 70 psia). The product from run 4 had an acid value of 10.8, indicating that the product from Run 1 (with a 2 hour residence time) is essentially at equilibrium.
95%Chromat. With sulfuric acid; for 4h;Reflux; General procedure: General procedure for the synthesis of compounds (6a-p); organic acid (0.40 mmol.), and catalyst (0.0005 mmol.) was combined with 20 mL ethanol in a 50 mL round bottomed flask equipped with a stir bar. Reaction was allowed to stir at reflux temperature for the appropriate amount of time (4 h). After completion of reaction, the reaction mixture was concentrated in vacuum to give a crude product which was analyzed by 1H NMR and GC-MS.
With zirconium containing 2-aminoterephthalate metal organic framework; at 78℃;Kinetics; General procedure: In view of the good catalytic activity and recyclability of UiO-type MOFs for the esterification of lauric acid with MeOH and EtOH,we wanted to investigate the applicability of the MOFs to otherbiomass derived free fatty acids with longer chain lengths, bothsaturated and unsaturated. Thus, we extended our study to theesterification with MeOH and EtOH of palmitic (hexadecanoic acid,C16), Stearic (octadecanoic acid, C18), Oleic (cis-9-octadecenoicacid C18:1), linoleic (cis,cis-9,12-octadecadienoic acid, C18:2) and-linolenic acids (cis,cis,cis-9,12,15-octadecatrienoic acid, C18:3).For the sake of brevity, the complete catalytic data obtained for eachfatty acid and the comparison with other acid catalysts from theliterature is provided as Supporting Information (Tables S1-S10).In order to illustrate the dependence of the chain length andunsaturation degree of the fatty acid on reaction rate, Fig. 3 showsthe calculated pseudo-first order reaction rate constants, k, of ester-ification of various fatty acids with ethanol over UiO-66-NH2. Thesame tendency was also observed for UiO-66, although this mate-rial was in general less active than UiO-66-NH2(as already observed C12 for C12 esterification commented above). As it can be observed, thereaction rate decreases as the chain length and the degree of unsa-turation of the fatty acid increases. This is probably due to higheradsorption of the unsaturated fatty acid (or fatty ester) on the sur-face of the solid, which causes the progressive deactivativation ofthe catalyst. However, it is worth mentioning that this deactivationdue to product adsorption is fully reversible, and the activity of thecatalysts is completely recovered by simply washing with EtOH.In conclusion, the above experiments demonstrates that bothZr-containing UiOs can efficiently catalyze the esterification of var-ious fatty acids with MeOH and EtOH, being less active as the alkylchain length and degree of unsaturation of the acid increases. It isalso worth mentioning that in all the reactions tested, the Zr-MOFswere found to be stable and reusable without significant loss ofactivity, as we have previously demonstrated for the esterificationof C12 with EtOH over UiO-66-NH2.
With trimethylcyclohexylammonium methanesulfonate; toluene-4-sulfonic acid; at 60℃; under 760.051 Torr; for 5h; According to the flow of Figure 2, the following processing is performed:2.5 mol of hexadecanoic acid, 2.5 mol of ethanol and 0.75 mol of octyltrimethylammonium methanesulfonate-p-toluenesulfonateThe molten solvent (the molar ratio of trimethylcyclohexylammonium methanesulfonate to p-toluenesulfonic acid is 1:2) is added to the esterification reactor to form the ester.The reaction vessel was heated to 60 C, and the reaction was stirred at normal pressure for 5 hours, and the stirring speed was 1000 rpm. After the reaction, the reaction solution is introduced into the decantationThe device was allowed to stand for phase separation and the rest time was 5 h. The upper liquid (ester phase) and the lower liquid (water) obtained after phase separation in the decanterThe phase is introduced into the washing tank and the flash tank respectively to carry out product ester purification and raw materials (mainly eutectic solvents, carboxylic acids and alcohols).Received. The working pressure of the washing tank is normal pressure, the operating temperature is room temperature, and the mass fraction is taken from the top of the washing tank.93% product ethyl hexadecanate, ie high purity ester, a mixture of eutectic solvent and water at the bottom, introduced into the flash tank; flashingThe tank has an operating pressure of 0.01 bar and an operating temperature of 200 C. The unreacted raw material is taken from the top of the flash tank and containsA mixture of water and ester with a eutectic solvent having a mass fraction of 99.99% at the bottom. Low eutectic solution obtained at the bottom of the flash tankThe agent is respectively exchanged to a temperature of 60 C through a heat exchanger and returned to the esterification reactor for recycling. Mixture produced at the top of the flash tankThe alcohol recovery tower is introduced, the actual number of trays of the alcohol recovery tower is 50, the operating pressure is normal pressure, the operation reflux ratio is 5.5, and the alcohol recovery towerThe unreacted alcohol was obtained from the top of the column, and was cooled to 60 C by a heat exchanger, and then returned to the esterification reactor for recycling. Recycling alcoholThe material of the Tata kettle is introduced into the carboxylic acid recovery tower. The actual number of plates in the carboxylic acid recovery column is 55, the operating pressure is normal pressure, and the operation is refluxed.The ratio is 4.2, the by-product water is obtained at the top of the acid recovery tower, and finally the water is removed from the esterification reaction system, and the acid recovery tower is obtained.The column kettle is obtained as a mixture containing unreacted carboxylic acid and a part of the product, and is cooled to 60 C by a heat exchanger to return to the esterification reaction.The kettle should be recycled. The yield of ethyl hexadecanate in Example 18 was 99.0%, and the purity was 93%.

References: [1]Synthetic Communications,2006,vol. 36,p. 7 - 11.
[2]Synthetic Communications,2014,vol. 44,p. 2386 - 2392.
[3]Patent: CN104311482,2017,B .Location in patent: Paragraph 0080; 0081; 0082; 0083; 0084; 0085-0091.
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[11]Ultrasonics Sonochemistry,2012,vol. 19,p. 387 - 389.
[12]Journal of Organic Chemistry,1983,vol. 48,p. 3106 - 3108.
[13]Bulletin de la Societe Chimique de France,1937,vol. <5> 4,p. 1667.
[14]Chemische Berichte,1936,vol. 69,p. 2279.
[15]Afinidad,1952,vol. 29,p. 354,356.
[16]Archiv der Pharmazie,1898,vol. 236,p. 433.
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[19]Patent: US2007/260077,2007,A1 .Location in patent: Page/Page column 4-5.
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[34]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2018,p. 671 - 678.
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YieldReaction ConditionsOperation in experiment
98% With ammonia; zircornium(IV) n-propoxide; at 165℃; for 7h; General procedure: According to the embodiment of the present invention described above, stearic acid amide, which is a kind of carboxylic acid amide compound, was prepared in Example 1 as follows. First, the carboxylic acid injector 250 injects 1000 g of stearic acid into the heater 100, and the heater 100 heats 1000 g of stearic acid to 120 C. Subsequently, when stearic acid is injected into the first reaction tank 210, the first catalyst injector 261 injects 10 g of tetraisopropyl titanium, which is a metal catalyst, into the first reaction tank 210, Was heated by the heater attached to the first reaction tank 210. When 150 g of stearic acid was charged into the first reaction tank 210, the first ammonia injector 281 started to feed the ammonia gas through the ammonia pipe 283 at a rate of 100 L / hr. When 500 g of stearic acid was charged into the first reaction tank 210, the introduction of stearic acid into the first reaction tank 210 was stopped. The propeller in the first reaction tank 210 was mixed with stearic acid and ammonia while maintaining the reaction temperature at 165 C in the first reaction tank 210.Next, when the supply of the stearic acid to the first reaction tank 210 is stopped, the 500 g of stearic acid remaining in the heater 100 through the valve is changed to be supplied to the second reaction tank 220. When stearic acid is injected into the second reaction tank 220, the second catalyst injector 262 injects 10 g of tetraisopropyl titanium as a metal catalyst into the second reaction tank 220 and starts heating the second reaction tank 220 . When 150 g of stearic acid was charged into the second reaction tank 220, the second ammonia feeder 282 started to feed the ammonia gas through the ammonia pipe 283 at a rate of 100 L / hr. When all 500 g of stearic acid was fed to the second reaction tank, the addition of stearic acid to the second reaction tank was stopped. The propeller in the second reaction tank 220 was mixed with stearic acid and ammonia while maintaining the reaction temperature of 165 C in the second reaction tank 220.In Examples 2 to 10, other carboxylic acid amide compounds were prepared in the same manner as in Example 1, except that stearic acid was used instead of stearic acid and other carboxylic acids as shown in the following Table 1 as "acid".
25% General procedure: To a stirred solution of the fatty acid (1.0 mmol, 1.0 equiv.) inCH2Cl2 (5 mL) was added CDI (0.178 g, 1.1 mmol, 1.1 equiv.).After 30 min at room temperature, the amine (1.1 mmol, 1.1equiv.) was added. After 12 h, CH2Cl2 (25 mL) was added, followedby saturated aqueous NH4Cl. The mixture was acidified topH 2 by addition of HCl, the organic phase was separated, andthe aqueous layer was further extracted with CH2Cl2 (3 × 10mL). The organic phases were combined, dried over Na2SO4, filtered,and concentrated in vacuo, to give the amide.
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YieldReaction ConditionsOperation in experiment
With sulfuric acid; at 18 - 35℃;Inert atmosphere; (1) 100 ml (about 184 g) 99-99.5% sulfuric acid was added to 250 ml four-neck flask with stirring, 35 g of palmitic acid was added at 30-35C dissolved with stirring for 0.5-1 hour. The temperature was dropped to 20-25C under protection of nitrogen, 17.6 grams of vitamin C was added with stirring, and stirring was stopped until completely dissolved, and insulated at 18-20C for 48 hours to obtain reaction liquid vitamin C palmitate. (2) The temperature was controlled to below 40C , the reaction solution was slowly poured into 200 ml 4-neck flask placed in ice-bath containing 200 ml cooling water. 700 ml of toluene was added and then subjected to extraction, heated to 60C and cooled naturally with stirring, when the temperature of the system was reduced to about 40C, stratified, and lower waste acid was separated leaving the toluene layer. (3) To the toluene layer 30-35 200 ml of water was added, stirred at 30-35C for 3 hours, crystallized at 30-35C for three hours, cooled in ice-water at 10-15C, stirred for one hour and filtered. The filter cake was washed with 50 ml of toluene, and then washed with 500 ml of water at 30-35C. (4) The filter cake was added to 500 ml water at 30-35C for 1 hour, filtered, and then washed with 200 ml water at 30-35C and the effluent water PH =7 was drained, discharged, and air-dried at room temperature for one day to constant weight. The crude product of vitamin C palmitate 33-34 g was obtained. Yield of 79.7-82.1%. (5) Take the above crude vitamin C palmitate, dissolved in 7.5 times the volume of 95% ethanol at 35-40 deg. C, filtered, washed with 0.5 volume of 95% ethanol and filtrate had crystallized, heated at 35-40C until fully dissolved and transferred to 500 ml 4-neck flask, rapidly cooled to -25--20C, crystallized by stirring for 3 hours, filtered, the filter cake was washed with 95% cold ethanol and vacuum-dried at 40-50C for 8 hours to obtain 30-31 g of product. Yield 90-92%.
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  • 3-(3,4-dimethoxyphenyl)propyl palmitate [ No CAS ]
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YieldReaction ConditionsOperation in experiment
78% With Novozyme 435 (from Candida antarctica immobilized on acrylic resin); Amberlyst A-21; In toluene; at 20℃; for 15.0h;Enzymatic reaction;Product distribution / selectivity; Example 28; Preparation of Retinyl Palmitate in the Presence of Amberlyst A-21; Retinyl acetate (1.00 g; 3.04 mmol) was dissolved in 8.5 mL of toluene and palmitic acid (1.56 g; 6.09 mmol; 2.0 equiv) was added followed by 120 mg of Novozyme 435 and 0.5g of dried Amberlyst A-21. The reaction mixture was stirred at RT for 15 h, at which point a sample was removed and analyzed by HPLC, indicating 89.2% conversion to retinyl palmitate with 9.1% retinyl acetate and 1.7% retinol. The reaction mixture was filtered and concentrated, then concentrated twice with heptane (10 mL each). The residue was dissolved in heptane (15 mL) and washed with 2×20 mL with a 1:1 mixture of 10% aqueous potassium carbonate and methanol. The organic layer was washed further with a mixture of saturated sodium bicarbonate (2.5 mL), water (7.5 mL), and methanol (10 mL), dried (sodium sulfate) and concentrated to afford 1.25 g (78%) of a yellow oil. Analysis of this product indicated 91.2% retinyl palmitate (HPLC area percent), 0.4 wt % palmitic acid, and 0.2% retinol. HPLC (4.6×150 mm Zorbax SB-C8 column [Agilent], 3.5mu thickness, methanol eluent, detection at 350 nm): tR 5.52 min (retinyl palmitate); tR 2.32 min (retinyl acetate); tR 2.08 min (retinol).
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YieldReaction ConditionsOperation in experiment
With novozyme 435; In toluene; at 20℃; for 20.0h;Schlenk technique; Inert atmosphere; Enzymatic reaction; General procedure: Retinyl esters were synthesized via an enzyme-catalyzed transesterification (19) as follows. Into a dry Schlenk flask, retinyl acetate (33 mg, 0.10 mmol), Novozyme 435 (120 mg), and AberlystA-21 (50 mg) were suspended in dry toluene (5 ml). The reaction mixture was stirred under an atmosphere of N2 , and five equivalents (0.50 mmol) of the appropriate acid (palmitic, stearic, linoleic, or oleic) were added. After 20 h at room temperature, the reaction mixture was filtered and the solvent was removed under reduced pressure to give a mixture (approximately 1:4) of the desired retinyl ester and unreacted acid. The resulting mixtures were used without further purification as LC/MS/MS standards for the corresponding retinyl esters.
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YieldReaction ConditionsOperation in experiment
With lipase from Pseudomonas stutzeri PS59; In aq. phosphate buffer; isopropyl alcohol; at 30℃; for 0.25h;pH 8.0;Enzymatic reaction; General procedure: An assay mixture consisting of 1 ml of liquid ester or 1 g of solid ester, 3 ml of isopropanol, 5 ml of phosphate buffer (pH=8.0), and 1 ml of the lipase solution was incubated for 15 min at 30C with stirring at 180 rpm. The reaction was terminated by the addition of 95% ethanol, and the amount of liberated fatty acids after incubation was determined by titrating with 50 mM NaOH in the presence of two drops of phenolphthalein solution as the indicator. The control experiment was performed under the same conditions with the addition of 95% ethanol prior to the reaction. One unit of lipase activity was defined as the amount of enzyme required to liberate 1 mumol of free fatty acid per minute under the experimental conditions.
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  • 5,8,11,14,17,20,23,26-octaoxa-2-azanonacosanedioic acid, 1-(9H-fluoren-9-ylmethyl) ester [ No CAS ]
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  • [ 47355-10-2 ]
  • [ 57-10-3 ]
  • C70H111N9O20S [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The second portion of the CCK4 peptide and the SubP peptide were modified on resin as follows to yield test lipidated peptides (1-SubP-COOH and 1-CCK4-Gly-COOH). Spacers (these are AA's used between the peg linker and the peptide of interest) were introduced on the peptides before pegylation (KGG for SubP and GG for CCK4). The free N-terminus of the peptide on resin was first pegylated with N-Fmoc-PEG8-propionic acid using standard HBTU coupling conditions. The N-Fmoc protecting group was removed by treatment with 10% piperidine in DMF (N,N-Dimethylformamide) for 5 min. Palmitic acid was subsequently coupled with the N-terminal free amine of the pegylated peptide. Peptides were cleaved from the resin using high HF conditions with minor modifications to the usual procedure. For the SubP peptide, longer times were used to ensure removal of Arg(Tos) protecting group (90% anhydrous HF/10% anisole at 0 C. for 2 h). For the CCK-4 peptides, 1,3-propanedithiol was used in the HF cleavage mixture to ensure deprotection of the formyl protecting group and prevent oxidation of methionine to its sulfoxide derivative: 85% anhydrous HF/10% anisole/5% PDT (1,3-propaneithiol) at 0 C. for 2 h) (Matsueda, 1982). Following cleavage from resin, peptides were precipitated with cold Et2O. Unmodified peptides were extracted using 10% AcOH in water and the lipidated peptides were extracted using 10% AcOH in H2O followed by 10% AcOH in 50% EtOH/H2O. Crude peptides were purified by RP-HPLC [Vydac C18, 10 m, 22 mm×250 mm]. The purities of the peptides were assessed by analytical RP-HPLC [Vydac C18, 5 m, 4 mm×250 mm].
  • 24
  • 5,8,11,14,17,20,23,26-octaoxa-2-azanonacosanedioic acid, 1-(9H-fluoren-9-ylmethyl) ester [ No CAS ]
  • [ 4530-20-5 ]
  • [ 15761-39-4 ]
  • [ 13139-15-6 ]
  • [ 2488-15-5 ]
  • [ 13734-34-4 ]
  • [ 13836-37-8 ]
  • [ 84624-27-1 ]
  • [ 54613-99-9 ]
  • [ 55260-24-7 ]
  • [ 57-10-3 ]
  • C111H185N21O28S [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The second portion of the CCK4 peptide and the SubP peptide were modified on resin as follows to yield test lipidated peptides (1-SubP-COOH and 1-CCK4-Gly-COOH). Spacers (these are AA's used between the peg linker and the peptide of interest) were introduced on the peptides before pegylation (KGG for SubP and GG for CCK4). The free N-terminus of the peptide on resin was first pegylated with N-Fmoc-PEG8-propionic acid using standard HBTU coupling conditions. The N-Fmoc protecting group was removed by treatment with 10% piperidine in DMF (N,N-Dimethylformamide) for 5 min. Palmitic acid was subsequently coupled with the N-terminal free amine of the pegylated peptide. Peptides were cleaved from the resin using high HF conditions with minor modifications to the usual procedure. For the SubP peptide, longer times were used to ensure removal of Arg(Tos) protecting group (90% anhydrous HF/10% anisole at 0 C. for 2 h). For the CCK-4 peptides, 1,3-propanedithiol was used in the HF cleavage mixture to ensure deprotection of the formyl protecting group and prevent oxidation of methionine to its sulfoxide derivative: 85% anhydrous HF/10% anisole/5% PDT (1,3-propaneithiol) at 0 C. for 2 h) (Matsueda, 1982). Following cleavage from resin, peptides were precipitated with cold Et2O. Unmodified peptides were extracted using 10% AcOH in water and the lipidated peptides were extracted using 10% AcOH in H2O followed by 10% AcOH in 50% EtOH/H2O. Crude peptides were purified by RP-HPLC [Vydac C18, 10 m, 22 mm×250 mm]. The purities of the peptides were assessed by analytical RP-HPLC [Vydac C18, 5 m, 4 mm×250 mm].
  • 25
  • [ 623-57-4 ]
  • [ 57-10-3 ]
  • bis(palmitoyloxy)-3-(dimethylamino)propane [ No CAS ]
  • 26
  • [ 623-65-4 ]
  • [ 57-10-3 ]
  • [ 50-81-7 ]
  • [ 137-66-6 ]
YieldReaction ConditionsOperation in experiment
91.3% (1)500g of concentrated sulfuric acid was added to the three-necked flask, add 50g of palmitic acid, stirring to dissolve Solution in concentrated sulfuric acid was added 50gL- ascorbic acid, 18 C reaction 15h; (2)50g palmitic anhydride was added to the reaction mixture, the temperature was raised to 28 C, the reaction 20h, then After adding 10g of activated carbon and stirred for 15min; (3)The step (2) in the resulting mixture is added to 1250ml10 C cold water, filtered The filter cake is too crude, the crude product was rinsed with 100ml water, then washed with water after the crude product was dissolved in 750ml of butyl acetate, 50 C incubation decolorization 30min. Filtered and allowed to stand, stratification, the upper organic layer (Product containing layer) 50 C, washed twice with water, water per 500ml. After washing to the water layer, The organic layer was distilled off under reduced pressure to 400ml of butyl acetate, allowed to stand for cooling to 15 C, the solid was filtered off with 50ml The resulting solid was rinsed with ethyl acetate, drained, placed in a vacuum drying oven at 50 C. L-ascorbic acid-6-palmitate was obtained as a white flake with a purity of 98. 1% and a yield of 91.3%.
  • 27
  • [ 56-86-0 ]
  • [ 57-10-3 ]
  • [ 616-45-5 ]
  • [ 3470-99-3 ]
  • [ 591-81-1 ]
  • [ 544-63-8 ]
  • [ 629-54-9 ]
  • 28
  • [ 53838-27-0 ]
  • [ 57-10-3 ]
  • N-hexadecanoyl-L-glutamic acid 5-tert-butyl-1-methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% In a 2000 mL dry bottom flask, palmitic acid (63.8 g, 248 mmol) was dissolved in 700 mL of dichloromethane at room temperature under argon atmosphere. Triethylamine (42.5 mL, 303 mmol) was then added drop wise and the mixture was stirred for 5 min. 2-(7-aza- lH-benzotriazole-l-yl)-l,l,3,3-tetramethyl uranium hexafluorophosphate (HATU) (115.59 g, 303 mmol) was added and allowed to stir for additional 10 min. In a separate round bottom flask, L-Glutamic acid tert-butyl ester (70 g, 276 mmol) was taken in 300 mL of dichloromethane and then added dropwise to the above activated palmitic acid in dichloromethane solution. The reaction mixture was allowed to stir at room temperature overnight. The suspension was filtered, quenched with water, extracted with dichloromethane and dried using sodium sulphate. It is then purified by silica gel column chromatography using methanol and dichloromethane to yield 5-t-butyl-l-methyl palmityl glutamate as a white solid (85 g, 180mmol, 65 % yield). ESI-MS (+ve) m/Z: 456.63(MH+).
  • 29
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • Fmoc-Asp(otbu)-OH [ No CAS ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-35-0 ]
  • [ 132327-80-1 ]
  • [ 57-10-3 ]
  • [ 32926-43-5 ]
  • [ 143824-78-6 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(γ-Glu-palmitoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The Wang resin (0.3 -0.6 mmol/g, loading capacity) was loaded to peptide synthesis vessel, washed twice with 10 v of MDC, decanted the washings, added 10 v of MDC and kept for swelling for 1 h. Fmoc-Gly-OH (3.0 - 5.0 eq.) was dissolved in MDC, added minimum quantity of DMF to obtain clear solution and the mixture was transferred to reaction vessel. Added DIPC (3.0 - 6.0 eq.) followed by DMAP (0.01- 0.1 eq.) to the reaction vessel and stirred for 1.0? 3.0 h, at rt. Drained the reaction mass and washed the amino acid loaded resin twice with MDC followed by DMF. Capping of the unreacted functional sites were carried out using acetic anhydride and DIPEA. Fmoc-deprotection of the loaded amino acid was carried out by washing the resin using 15-25 percent piperidine in DMF two times for 5 and 10 min. followed by the resin was washed with 3-5*8 v 0.01? 0.1 M HOBt in DMF. The Fmoc-Arg(Pbf)-OH (2.0? 4.0 eq.), was coupled using coupling agents such as HBTU, COMU, DEPBT, and DIC, preferably DEPBT (2.0 - 4.0 eq.) and oxymapure, HOBt, preferably oxymapure (2.0? 4.0 eq.) and DIPEA, NMM, TMP, preferably DIPEA (5.0 -8.0 eq.) and MgCl2, ZnCl2, preferably MgCl2 (0.01? 0.1 eq) and DMF/NMP mixture as solvent. The reaction was performed in nitrogen atmosphere and r.t. Upon completion of coupling of the amino acid confirmed by Kaiser Test, the excess reagents were drained and washed the peptidyl resin with 3 x 10 v DMF
  • 30
  • [ 50584-68-4 ]
  • [ 57-10-3 ]
  • panthenyl monopalmitate [ No CAS ]
  • 31
  • [ 88574-06-5 ]
  • [ 57-10-3 ]
  • [ 145038-49-9 ]
  • C28H52N2O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% Molecule A27 is obtained by means of the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (24.00 g, 1.37 mmol/g). (1288) The grafting of the first amino acid Fmoc-6-aminohexanoic acid (1.5 equivalents) is performed in DCM (10 V), in the presence of DIPEA (2.5 equivalents). The unreacted sites are capped with methanol (0.8 mL/g resin) at the end of the reaction. (1289) The protected amino acid <strong>[145038-49-9]Fmoc-Glu-OMe</strong> (1.5 equivalents) and palmitic acid (1.5 equivalents) are coupled in DMF (10 V), in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (1.5 equivalents with respect to the acid). (1290) The protecting groups Fmoc are removed using an 80:20 DMF/piperidine solution (10 V). (1291) The product is cleaved from the resin using an 80:20 DCM/HFIP solution (10 V). (1292) After concentration at reduced pressure, two co-evaporations are performed on the residue with dichloromethane followed by toluene. The product is purified by recrystallization in ethyl acetate. A white solid of molecule A27 is obtained. (1293) Yield: 11.54 g (68% in 6 stages) (1294) 1H NMR (CDCl3, ppm): 0.88 (3H); 1.19-1.35 (24H); 1.35-1.44 (2H); 1.50-1.70 (6H); 1.91-2.01 (1H); 2.14-2.40 (7H); 3.14-3.34 (2H); 3.75 (3H); 4.51-4.59 (1H); 6.53 (1H); 6.70 (1H). (1295) LC/MS (ESI+): 513.4 (calculated ([M+H]+): 513.4).
  • 32
  • [ 88574-06-5 ]
  • [ 57-10-3 ]
  • [ 145038-49-9 ]
  • C28H52N2O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
11.54 g Molecule A27 is obtained by means of the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (24.00 g, 1.37 mmol/g). The grafting of the first amino acid Fmoc-6-aminohexanoic acid (1.5 equivalents) is performed in DCM (10 V), in the presence of DIPEA (2.5 equivalents). The unreacted sites are capped with methanol (0.8 mL/g resin) at the end of the reaction. The protected amino acid <strong>[145038-49-9]Fmoc-Glu-OMe</strong> (1.5 equivalents) and palmitic acid (1.5 equivalents) are coupled in DMF (10 V), in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (1.5 equivalents with respect to the acid). The protecting groups Fmoc are removed using an 80:20 DMF/piperidine solution (10 V). The product is cleaved from the resin using an 80:20 DCM/HFIP solution (10 V). After concentration under reduced pressure, two co-evaporations are performed on the residue with dichloromethane followed by toluene. The product is purified by recrystallization in ethyl acetate. A white solid of molecule A27 is obtained. Yield: 11.54 g (68% in 6 stages) 1H NMR (CDCl3, ppm): 0.88 (3H); 1.19-1.35 (24H); 1.35-1.44 (2H); 1.50-1.70 (6H); 1.91-2.01 (1H); 2.14-2.40 (7H); 3.14-3.34 (2H); 3.75 (3H); 4.51-4.59 (1H); 6.53 (1H); 6.70 (1H). LC/MS (ESI+): 513.4 (calculated ([M+H]+): 513.4).
 

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