Racemic or optically active D- or L-α-glycerophosphoryl choline solids are prepared from liquid type racemic or optically active D- or L-α-glycerophosphoryl choline using an organic solvent. The solids are produced at a high yield more easily through phase transformation than an existing method using a difference in solubility in a solvent.
The present invention is characterized in that racemic or optically active D- or L-α-glycerophosphoryl choline solids are prepared from liquid type racemic or optically active D- or L-α-glycerophosphoryl choline using an organic solvent. The present invention can produce solids at a high yield more easily through phase transformation rather than a method using a difference in solubility in a solvent, which is an existing method.
A method of preparing racemic or optically active D or L-α-glycerophosphorylcholine in large amounts by subjecting choline phosphate or a salt thereof, and racemic or optically highly pure (S) or (R)-3-halo-1,2-propanediol to a substitution reaction in a medium at high temperature in the presence of an inorganic base which increases the activity of the reaction. The method is cost-effective because of the use of starting materials which are inexpensive compared to those in a conventional method. Moreover, the method is simple and convenient because it is performed via a one-pot reaction without a separate purification process. In addition, it enables a large amount of racemic or optically active D or L-α-glycerophosphorylcholine, or a salt thereof, to be quantitatively produced in a medium without side reactions by using the inorganic base which increases the reaction activity.
The present invention is characterized in that racemic or optically active D- or L-α―glycerophosphoryl choline solids are prepared from liquid type racemic or optically active D- or L-α―glycerophosphoryl choline using an organic solvent. The present invention can produce solids at a high yield more easily through phase transformation rather than a method using a difference in solubility in a solvent, which is an existing method.
C07F 9/113 - Esters des acides phosphoriques avec des alcools acycliques non saturés
C07B 55/00 - RacémisationInversion complète ou partielle
A61K 31/661 - Acides du phosphore ou leurs esters n'ayant pas de liaison P-C, p. ex. fosfosal, dichlorvos, malathion
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
5.
METHOD FOR PREPARING RACEMIC OR OPTICALLY ACTIVE Α―GLYCEROPHOSPHORYL CHOLINE
The present invention relates to a method for preparing racemic or optically active α―glycerophosphoryl choline and, more specifically, to a method for mass-producing racemic or optically active D- or L-α―glycerophosphoryl choline through a substitution reaction of choline phosphate or a salt thereof and racemic or optically pure (S) and (R)-3-halo-1,2-propandiols in the presence of a medium using an inorganic base which increases activity of the reaction at a high temperature. The method for preparing racemic or optically active D- or L-α―glycerophosphoryl choline according to the present invention is economical by using a low-priced starting material compared with the conventional method, provides a convenient preparation procedure by performing a one-pot reaction without a separate purification procedure, and can quantitatively mass-produce racemic or optically active D- or L-α―glycerophosphoryl choline and a salt thereof in the presence of a medium without a side reaction by using an inorganic base which increases activity of the reaction.
The present invention relates to a method for preparing Clopidogrel and its derivatives. More particularly, the present invention is a method for preparation of (S)-2-Clopidogrel and its derivatives, which are active inhibitors of platelet aggregation, from an optically active (S)-2-chlorophenylglycine alkyl ester through hydrolysis of racemic 2-chlorophenylglycine alkyl esters using an enzyme. The present invention employs a simple procedure to prepare Clopidogrel and its derivatives. Because no chiral resolving agents are used except for a small amount of enzyme, the cost of preparation can be reduced. In addition, the present invention is suitable for synthesizing highly optical-active Clopidogrel and its derivatives on a large scale by using optically active (S)-2-chlorophenylglycine alkyl ester obtained in high yield as an intermediate, and is also environmentally friendly since no highly toxic reagents are employed.
Provided is a process for preparing L-carnitine or acetyl L-carnitine hydrochloride. Specifically, the process comprises sequentially synthesizing racemic 4-chloro-3-hydroxybutyronitrile and racemic 4-chloro-3-hydroxy butyric acid alkyl ester under specific reaction conditions, using racemic epichlorohydrin as a starting material, preparing (R)-4-chloro-3-hydroxy butyric acid alkyl ester from stereoselective hydrolysis of the racemic 4-chloro-3-hydroxy butyric acid alkyl ester using an enzyme, and preparing L-carnitine or acetyl L-carnitine hydrochloride from the (R)-4-chloro-3-hydroxy butyric acid alkyl ester, according to the known method.
C07C 229/22 - Composés contenant des groupes amino et carboxyle liés au même squelette carboné ayant des groupes amino et carboxyle liés à des atomes de carbone acycliques du même squelette carboné le squelette carboné étant acyclique et saturé le squelette carboné étant substitué de plus par des atomes d'oxygène
8.
THE METHOD OF MAKING OPTICALLY ACTIVE 2-HALO-2-(N-SUBSTITUTED PHENYL)ACETIC ACID ESTERS AND 2-HALO-2-(N-SUBSTITUTED PHENYL)ACETIC ACIDS BY ENZYMATIC METHOD
The present invention relates to the process for the preparation of optically active 2-halo-2-(n-substituted phenyl)acetic acid esters and optically active 2-halo-2-(n-substituted phenyl)acetic acids, which are used intensively as important chiral intermediates, represented by general formula 2 and 3 respectively from racemic 2-halo-2-(n-substituted phenyl)acetic acid ester represented by general formula 1. In more detail, this invention relates to the process for preparing optically active 2-halo-2-(n-substituted phenyl)acetic acid esters and optically active 2-halo-2-(n-substituted phenyl)acetic acids by stereospecific hydrolysis of racemic 2-halo-2-(n-substituted phenyl)acetic acid esters using hydrolases or hydrolase-producing microorganisms in the aqueous phase or organic phase including aqueous solvent. This method is useful in the practical process because the production and separation of compounds with high optical purity is easier.
The present invention relates to the process for the preparation of L-carnitine from racemic 3-acyloxy-gamma-butyrolactone or alkyl (R)-4-chloro-3-hydroxybutyrate. In more detail, this present invention relates to the process for the preparation of L-carnitine from (R)-3-hydroxy-gamma-butyrolactone, which was produced from racemic 3-acyloxy-gamma-butyrolactone by stereospecific hydrolysis using enzyme in the aqeous phase or organic phase including aqeous solvent or alkyl (R)-4-chloro-3-hydroxybutyrate, followed by a ring-opening reaction, epoxydation and a nucleophilic substitution by trimethylamine to prepare L-carnitine. The method of making L-carnitine is easier and more economical comparing to the con¬ ventional methods and L-carnitine produced has higher optical purity.
C07D 303/40 - Composés contenant des cycles oxirane avec des radicaux hydrocarbonés substitués par des atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile par des radicaux ester
10.
THE METHOD OF MAKING OPTICALLY ACTIVE 2-CHLOROMANDELIC ACID ESTERS AND 2-CHLOROMANDELIC ACIDS BY ENZYMATIC METHOD
The present invention relates to process for the preparation of optically active 2-chloromandelic acid esters represented by the general formula 2 and optically active 2-chloromandelic acids represented by the general formula 2 which are used intensively as important chiral intermediates. In more detail, this invention relates to the process for preparing optically active 2-chloromandelic acid esters and optically active 2-chloromandelic acids by stereospecific hydrolysis of racemic 2-chloromandelic acid ester using lipases or lipase-producing microorganisms in the aqeous phase or organic phase including aqeous solvent. The method of making optically active 2-chloromandelic aicd esters and their acids is usful in the practical process because production of seperation of compounds with high optical purity are easy.
The present invention relates to the process for preparing optically active 3-acyloxy-gamma-butyrolactone repesented by the general formula 5 and optically active 3-hydroxy-gamma-butyrolactone represented by the general formula 6 in scheme 1 from racemic 3-acyloxy-gamma-butyrolactone repesented by the general formula 4 by enzymatic method. In more detail, this invention relates to the process for the preparation of optically active 3-acyloxy-gamma-butyrolactone and optically active 3-hydroxy-gamma-butyrolactone wherein racemic epichlorohydrin represented by the general formula 1 is subjected to produce racemic 4-chloro-3-hydroxybutyronitrile, racemic 3-hydroxy-gamma-butyrolactone and racemic 3-acyloxy-gamma-butyrolactone in turn and racemic 3-acyloxy-gamma-butyrolactone is hydrolyzed sterospecifically using lipases or lipase-producing microorganisms in the aqeous phase or organic phase containing water. This method is useful in the practical process because production and seperation of compounds with high optical purity are easy comparing with other reported process.
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