sn-glycero-3-Phosphocholine

L-Alpha glycerylphosphorylcholine (alpha-GPC, choline alfoscerate) is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have potential for the treatment of Alzheimer's disease and dementia.IC50 value:Target: Anti-ADAlpha-GPC rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of the acetylcholine neurotransmitter. It is a non-prescription drug in most countries due

Solid

Choline alfoscerate is a member of the class of phosphocholines that is the choline ester of sn-glycero-3-phosphate. It is one of the major osmolyte in the renal medullary cells. It has a role as a parasympatholytic, a neuroprotective agent, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a member of sn-glycerol 3-phosphates and a member of phosphocholines.|A component of PHOSPHATIDYLCHOLINES or LECITHINS, in which the two hydroxy groups of GLYCEROL are esterified with fatty acids. (From Stedman, 26th ed)

10 g of phosphorylcholine chloride (1 equivalent, 228 mmol) was dissolved in 200 ml of methanol in a 500 ml three-necked round bottom flask equipped with a thermometer, a reflux condenser and a stirrer. Then, 5.1 g of potassium hydroxide (2 equivalents, 455 mmol) Lt; / RTI & gt; and stirred for 1 hour. After warming the reaction to 65 ° C, 10 g of (R) -3-chloro-1, 2-propanediol (2 eq, 452 mmol) was added slowly and refluxed for 16 hours to carry out the substitution reaction.After completion of the reaction, 10 ml of water was added to the concentrate obtained by concentration under reduced pressure, and the reaction product was diluted with acetone twice. The aqueous layer was concentrated under reduced pressure to obtain 11.60 g of L-α-glycerophosphorylcholine (yield: 99percent) .The oil like dissolved in 120 g of water in methanol, adding potassium carbonate 5 g as capture, dropping (R)-4 - chloromethyl - 2, 2 - dimethyl - 1, 3 - dioxolane 36 g, the completion of the dropping, the reaction temperature is controlled 65 °C reflux reaction for about 18 hours, after the completion of reaction, adding 150 g 8percent hydrochloric acid hydrolysis, hydrolysis after the end of the, concentrated under reduced pressure to obtain Ganong choline phosphate crude, adding 120 g methanol dissolved, Buchner funnel filter, the filtrate through the macroporous ion exchange resin adsorption, the flow rate control is 1000 ml/h, TLC analysis after detecting Ganong choline phosphate, the obtained GaN choline phosphate aqueous solution. The 127 g 201x7 anionic resin with 30 g 001x7 cationic resin to mix evenly, is inserted into the mixing in the bed, the above-mentioned GaN choline phosphate aqueous solution filtered mixed bed, filtration, concentration, to obtain 36 g colorless transparent oily matter, the water content is 15.3percent, Ganong choline phosphate chemical purity of 99.7percent, the specific optical rotation is -2.82 °, the overall yield is 65.1percent.198 g (1.0 mol) of (R)-3-glycerylcycloethyl phosphate of Example 3 was taken. It was mixed with 1500 ml of absolute ethanol, and 177 g (3.0 mol) of trimethylamine was added thereto, and the mixture was reacted at room temperature for 5 hours. The TLC check was complete. The developing solvent was diethyl ether-petroleum ether (3:1), Rf = 0.42. After the reaction, concentrated under reduced pressure, The solvent and excess trimethylamine are removed to precipitate a solid product. Anhydrous ethanol: isopropanol = 3:1 recrystallization (W/W), Filtering, vacuum drying at 50 ° C for 4 h, 236.76 g of white solid, yield 92.11percentAdd in the reactorPhosphorylcholine calcium salt (usually tetrahydrate) 330g and 300ml water, Stir until dissolvedA sodium carbonate solution with a concentration of 50percent made of anhydrous sodium carbonate (106 g) and water was dropped and dropped at a rate of 10 ml/min. After the dropwise addition, the mixture was stirred at room temperature for 1 hour. The salt solution was passed according to the solubility of sodium chloride. Precipitation of sodium chloride in the reaction systemfilter. The filtrate was passed through a sulfonic acid ion column and eluted with water several times to HPLC without product.The solvent was distilled under reduced pressure and concentrated to a volume of 300 ml.66 g of (R)-chiral glycidol was added, and the reaction was stirred at reflux for 2-6 hours. HPLC showed no raw material, and the water was evaporated under reduced pressure and recrystallized from methanol to obtain 289 g of product. (HPLC > 99.7percent)2) refluxing the mixture M1 and 3g of (R)-3-chloro-1, 2-propanediol in absolute ethanol to obtain a mixture M2, 3)The mixture M2 is diluted five times and then flows through the cation exchange resin to obtain a mixture M3; 4) The mixture M3 is diluted twice and then passed through the cation exchange resin to obtain a mixture M4, 5) Mixture M4 is washed with 70percent by weight ethanol to obtain a mixture M5; 6) After the mixture M5 was washed with distilled water to obtain a mixture M6; 7) After the mixture M6 flows through the cation exchange resin and the anion exchange resin, the filtrate is filtered and the filtrate is distilled under reduced pressure to obtain glycerophosphatidylcholine A2. (Amount of product 7.8 g, purity 100percent, pH 6.5, optical rotation -2.8 °)

L-Alpha glycerylphosphorylcholine (alpha-GPC, choline alfoscerate) is a natural choline compound found in the brain. It is also a parasympathomimetic acetylcholine precursor which may have potential for the treatment of Alzheimer's disease and other dementias.Alpha-GPC rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of acetylcholine. It is a non-prescription drug in most countries and in the United States it is classified as generally recognized as safe (GRAS).

Molecular Weight:257.22
XLogP3:-2.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:8
Exact Mass:257.10282436
Monoisotopic Mass:257.10282436
Topological Polar Surface Area:99
Heavy Atom Count:16
Complexity:233
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes