987-78-0

Basic information

• Product Name: CYTIDINE 5'-DIPHOSPHOCHOLINE
• Synonyms: Cytidine 5'-(trihydrogen diphosphate), P'-[2-(trimethylammonio)ethyl] ester, inner salt;Difosfocin;Emicholine F;Haocolin;Hornbest;Neucolis;NSC 122002;Reagin
• CAS NO: 987-78-0
• Molecular Formula: C₁₄H₂₆N₄O₁₁P₂
• Molecular Weight: 488.32
• EINECS: 213-580-7
• Product Categories: Pharmaceutical Intermediates;ZOLOFT
• Mol File: 987-78-0.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 851.4°C at 760 mmHg
• Appearance: White powder
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• Solubility: Water (Sparingly)
• PKA: 4.4(at 25℃)
• Stability: Moisture Sensitive
• CAS DataBase Reference: CYTIDINE 5'-DIPHOSPHOCHOLINE(CAS DataBase Reference)
• NIST Chemistry Reference: CYTIDINE 5'-DIPHOSPHOCHOLINE(987-78-0)
• EPA Substance Registry System: CYTIDINE 5'-DIPHOSPHOCHOLINE(987-78-0)

Safety Data

• Hazardous Substances Data: 987-78-0(Hazardous Substances Data)

Usage

Originator

Nicholin,Cyanamid,Italy,1971

Uses

Cytidine 5'-Diphosphocholine is used as antidepressant, 5HT uptake inhibitor.

Manufacturing Process

A 250 ml conical flask containing 30 ml of a reaction liquor (pH 7.0) having a composition of 7.38 mg/ml of disodium salt of CMP (cytidine-5'- monophosphate), 24 mg/ml of choline, 10 mg/ml of glucose, 100 mg/ml of acetone-dried cells of Brevibacterium ammoniagenes ATCC 6872, 11.6 mg/ml of monopotassium phosphate, 20 mg/ml of dipotassium phosphate and 2.96 mg/ml of magnesium sulfate, (MgSO4·7H2O), was subjected to culturing at 30°C for 4 hours. Cytidine diphosphate choline was formed and accumulated at a concentration of 3.8 mg/ml in the culture liquor. The pH of 1.2 liters of filtrate containing 3.8 mg/ml of cytidine diphosphate choline, obtained by removing solid matters from the culturing liquor, was adjusted to a pH of 8.5 with a 0.5 N KOH solution. The filtrate was passed through a column of strongly basic anion exchange resin, Dowex 1 x 2 (formic acid type). After washing the resin with water, a formic acid solution was passed through the column with gradual increase in the concentration of formic acid (until 0.04 N max.). A fraction of cytidine diphosphate choline was collected by elution according to the so-called gradient elution method and absorbed onto carbon powders. Then, elution was effected with acetone, and the eluate was concentrated and dried. 1.3 g of cytidine diphosphate choline powders were obtained.

Therapeutic Function

Cerebral circulation stimulant

InChI:InChI=1/C12H22N4O11P2/c1-16(2,3)26-29(22,23)27-28(20,21)24-6-7-9(17)10(18)11(25-7)15-5-4-8(13)14-12(15)19/h4-5,7,9-11,17-18H,6H2,1-3H3,(H3-,13,14,19,20,21,22,23)/t7-,9-,10-,11-/m1/s1

Upstream product

• 17804-69-2 trimethyl-(2-phosphono-ethyl)-ammonium 
• 63-37-6 cytidine monophosphate 
• 30784-94-2 cytidine-5'-phosphodichloride 
• 4826-71-5 phosphorylcholine chloride, calcium salt 
• 76742-17-1 cytidine 5'-monophosphate morpholidate 
• 75-50-3 trimethylamine 
• 107-73-3 phosphorylcholine chloride 
• 65062-75-1 O^2',O^3'-carbonyl-[5']cytidylic acid 
• 492-62-6 alpha-D-glucopyranose 
• 67-48-1 choline chloride 
• 65-86-1 orotic acid 

Downstream Products

• 33818-15-4 cytidine 5'-diphosphocholine sodium salt 
• 6753-55-5 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine 

Relevant articles and documents

Improved synthesis of cytidine diphosphate choline (CDP-choline) via selective phosphorylation

An improved, three-step synthesis of cytidine diphosphate choline (CDP-choline) from cytidine was achieved in 68% overall yield. Selective phosphorylation of cytidine was accomplished by the use of morpholinophosphodichloridate to give cytidine-5′-phosphomorpholide, which was condensed with choline phosphate chloride in the presence of a catalytic amount of H2SO4 to give CDP-choline. The intermediates and products could be efficiently purified by recrystallisation, thus avoiding the use of chromatography at all stages. The reaction could be scaled up to 200 g in 64% overall yield, making this route attractive for industrial application.

Citicoline and synthetic method thereof

The invention discloses citicoline and a synthetic method thereof.The synthetic method includes subjecting cheap and easily available cytidine, serving as a raw material, and dichlorophosphoryl morpholine to condensation at a 5' position highly selectively so as to obtain 5'-phosphorylmorpholinylcytidine; subjecting the 5'-phosphorylmorpholinylcytidine and phosphocholine chloride calcium to condensation in solvents so as to obtain the citicoline.Total yield is up to 58% only by the two steps.The synthetic method is cheap in and easily available to raw materials, expensive cytidine monophosphate is unused, operation steps are simplified, and reaction scale can be expanded to synthesize 500 g of citicoline.The synthetic method has a potential application prospect by providing a novel citicoline synthetic route.

Citicoline and synthesizing method of citicoline not using phosphocholine chloride calcium

The invention discloses citicoline and a synthesizing method of citicoline not using phosphocholine chloride calcium. The synthesizing method does not use phosphocholine chloride calcium, and comprises the following three steps of using dichloride phosphoryl morpholine with low cost and easy obtaining as a raw material, and reacting with ethylene glycol, so as to obtain glycol ester phosphoryl morpholine; continuously and directly is in condensation with cytidine monophosphate, so as to obtain glycol ester phosphoryl cytidine monophosphate; finally, opening a loop of gylcol ester of the glycol ester phosphoryl monophosphate by tributylamine, so as to obtain the citicoline, wherein the total yield is 78 percent. The synthesizing method has the advantages that the cost of raw material is low, and the obtaining is easy, so that the use of DCC (dicyclohexylcarbodiimide) and phosphocholine chloride calcium with high cost and toxicity is avoided; when the reaction scale is expanded to 500g, the yield is not obviously decreased; a new synthesizing path is provided for the synthesis of the citicoline, and the potential application prospect is realized.

CDP-Ethanolamine and CDP-Choline: One-pot synthesis and 31P NMR study

Herein we report a one-pot multi-step synthesis of the cofactors CDP-Ethanolamine and CDP-Choline starting from cytidine 5′-monophosphate and using commercially available and/or easily prepared reagents. While studying the 31P NMR spectrum of CDP-Ethanolamine, an unexpected characteristic for a pyrophosphate diester was observed as it showed a singlet or two doublets depending upon the pH. Therefore, further NMR studies were undertaken to investigate the pH dependence of the peak splitting pattern and measure the acid dissociation constants of the compounds.

METHOD FOR PURIFICATION OF CYTIDINEDIPHOSPHORIC CHOLINE

A method of purifying cytidine diphosphate choline, which comprises contacting a cytidine diphosphate choline solution containing a nucleic acid analogue and having a pH of not less than 0.5 and not more than 5.0 with an H-type strongly acidic cation exchange resin, and eluting cytidine diphosphate choline adsorbed onto the resin with water or an aqueous solution having an ion concentration of not more than 0.1 mol/L to separate and purify the cytidine diphosphate choline.