- PROCESS FOR THE PRODUCTION OF CARNITINE BY CYCLOADDITION
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The invention relates to a method for the production of L-carnitine, wherein a chiral β-lactone carnitine precursor is obtained by a [2+2] cycloaddition of ketene with an aldehyde X—CH2—CHO, wherein X is selected from Cl, Br, I and trimethylamine, in the presence of a chiral catalyst.
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Page/Page column 10
(2012/02/03)
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- PROCESS FOR PRODUCTION OF BETAINE
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According to the present invention, by using 4-halogeno-3-hydroxybutanamide as a substrate in quaternary amination reaction with trialkylamine which is an important step in betaine (such as carnitine) preparation processes, it becomes possible to reduce the production of crotonic acid derivatives (the major by-product) greatly compared to conventional processes. Consequently, it becomes possible to prepare a betaine, such as carnitine, at a high yield. The present invention also relates to a process for preparing a betaine represented by formula (1) below, comprising a step of quaternary aminating an amide represented by formula (2) below: wherein A1, A2 and A3 individually represent a C1-C20 hydrocarbon group which may have a substituent(s); and X1 is a halogen atom.
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Page/Page column 24
(2009/09/26)
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- CARNITINE CONJUGATES AS DUAL PRODRUGS, METHODS OF PRODUCTION AND USES THEREOF
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The present invention discloses novel dual prodrug compounds of formula (1), methods for their preparation and intermediates in their syntheses, formula (1): wherein A is a single bond, -0-, or -CH2-; m and n vary independently and are an integer from 1 to 15; p and q vary from 0 to an integer from 1 to 4; B is a single bond or -CR3R4; D is formula (2): or formula (3): and X is halogen; R1 to R4 are various substituents selected to optimize the physiochemical and biological properties such as, lipophilicity, bioavailability, and pharmacokinetics of compounds of Formula 1; and R1 and R2 or R3 and R4 may optionally be tethered together to form a 3- to 7-membered alicyclic ring. These compounds are useful for the treatment of various infections, metabolic, cardiovascular and neurological disorders.
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Page/Page column 29
(2010/11/30)
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- An efficient, highly enantioenriched route to L-carnitine and α-lipoic acid via hydrolytic kinetic resolution
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A general and practical approach for the synthesis of C-4 chiral building blocks using Jacobsen's hydrolytic kinetic resolution technique to resolve terminal epoxides and diols in high enantiomeric excess and excellent yields is described. The utilization of these building blocks for the synthesis of biologically important natural products L-carnitine and α-lipoic acid is illustrated. Georg Thieme Verlag Stuttgart.
- Bose, D. Subhas,Fatima, Liyakat,Rajender, Salla
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p. 1863 - 1867
(2008/01/27)
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- Stabilization of polynucleotide complexes
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Polynucleotide complexes are stabilized by adding a cryoprotectant compound and lyophilizing the resulting formulation. The lyophilized formulations are milled or sieved into a dry powder formulation which may be used to deliver the polynucleotide complex. Delivery of the polynucleotide to a desired cell tissue is accomplished by contacting the tissue with the powder to rehydrate it. In a preferred embodiment, a dry powder formulation is used to induce genetic modification of a patient's lung tissue.
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- Dialysis solutions containing water soluble vitamins and nutrients
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The invention relates to methods and compositions for the prevention and treatment of vitamin and other nutrient deficiencies in hemodialysis and peritoneal dialysis patients. Patients are dialyzed with a dialysate solution comprising at least one vitamin.
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- Retention and selectivity of teicoplanin stationary phases after copper complexation and isotopic exchange
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Teicoplanin is a macrocyclic glycopeptide that is highly effective as a chiral selector for LC enantiomeric separations. Two possible interaction paths were investigated and related to solute retention and selectivity: (1) interactions with the only teicoplanin amine group and (2) role of hydrogen bonding interactions. Mobile phases containing 0.5 and 5 mM copper ions were used to try to block the amine group. In the presence of copper ions, it was found that the teicoplanin stationary phase has a decreased ability to separate most underivatized racemic amino acids. However, it maintained its ability to separate enantiomers that were not α - amino acids. It is established that there is little copper - teicoplanin complex formation. The effect of Cu2+ on the enantioseparation of some α - amino acids appears to be due to the fact that these solutes are good bidentate ligands and form complexes with copper ions in the mobile phase. Isotopic exchange with deuterium oxide was performed using acetonitrile - heavy water mobile phases. It was found that the retention times of all amino acids were lower with deuterated mobile phases. The retention times of polar or apolar molecules without amine groups were higher with deuterated mobiles phases. In all cases, the enantio-selectivity factors were unaffected by the deuterium exchange. It is proposed that the electrostatic interactions are decreased in the deuterated mobile phases and the solute-accessible stationary-phase volume is somewhat swollen by deuterium oxide. The balance of these effects is a decrease in the amino acid retention times and an increase in the apolar solute retention time. The enantio-selectivity factors of all of the molecules remain unchanged because all of the interactions are changed equally. We propose a new global quality criterion (the E factor) for comparing and evaluating enantiomeric separations.
- Berthod,Valleix,Tizon,Leonce,Caussignac,Armstrong
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p. 5499 - 5508
(2007/10/03)
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- Asymmetric synthesis of (S)-(+)-carnitine and analogs
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A general asymmetric route to enantiomerically pure (S)-(+)-carnitine and analogs has been investigated that involves mono-addition of organometallic reagents to the lactone carbonyl group of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin- 2-one and Lewis acid promoted stereoselective allylation of the resulting hemiacetals. The diastereomerically pure allyl oxazines thus obtained were readily converted into enantiomerically pure (S)-(+)-carnitine and two substituted analogs.
- Jain, Rajendra P,Williams, Robert M
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p. 6505 - 6509
(2007/10/03)
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- Hydrolytically cleavable active ingredient derivative compounds, hair treatment compositions containing them and hair treatment methods
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The new active ingredient derivative compounds have the formula (I) STR1 wherein R1, R2 and R3 are the same or different and are each an unsubstituted or substituted alkyl group, Y is an unsubstituted or substituted alkylene group, R is an active ingredient group which, prior to ester formation, has at least one OH group and A- is an anion. A process for making the compounds of formula (I) is described. Hair treatment compositions containing these compounds and methods of treating hair with these hair treatment compositions are also described.
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- Dry powder formulations of polynucleotide complexes
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Polynucleotide complexes are stabilized by adding a cryoprotectant compound and lyophilizing the resulting formulation. The lyophilized formulations are milled or sieved into a dry powder formulation which may be used to deliver the polynucleotide complex. Delivery of the polynucleotide to a desired cell tissue is accomplished by contacting the tissue with the powder to rehydrate it. In a preferred embodiment, a dry powder formulation is used to transfer genetic information to the cells of the respiratory tract.
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- Compositions and methods for enhanced drug delivery
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The present invention relates to methods of delivering pharmaceutical agents across membranes, including the skin layer or mucosal membranes of a patient. A pharmaceutical agent is covalently bonded to a chemical modifier, via a physiologically cleavable bond, such that the membrane transport and delivery of the agent is enhanced.
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- Phosphinyloxy propanaminium inner salt derivatives
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Compounds of the formula STR1 where X1 and X2 are independently O or S, and R1 is as defined in the description R2, R3, and R4 are each independently straight or branched chain (C1-4)alkyl, and pharmaceutically acceptable salts, physiological hydrolysable esters, and pro-drug forms thereof are useful as hypoglycemic agents.
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- Process for preparing phosphinyloxy propanaminium inner salt derivatives
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A process for preparing compounds of the formula STR1 where X1 and X2 are independently O or S, and R1 is as defined herein, R2, R3, and R4 are each independently straight or branched chain (C1-4)alkyl, and pharmaceutically acceptable salts, physiological hydrolyzable esters, and pro-drug forms thereof, which are useful as hypoglycemic agents.
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- A new, short and efficient synthesis of both enantiomers of carnitine
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A short, efficient and enantioselective synthesis of both (R) and (S) enantiomers of carnitine is reported starting with (R) or (S) malic acid and involving a chemoselective reduction step.
- Bellamy,Bondoux,Dodey
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p. 7323 - 7326
(2007/10/02)
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- Process for preparing 3 halogeno-2-hydroxypropyltrimethylammonium halide
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A process for preparing 3-halogeno-2-hydroxy-propyltrimethylammonium halide or especially one having the (S)-configuration, which comprises reacting 2,3-dihydroxypropyltrimethylammonium halide or one having the (S)-configuration, which is obtained by reacting (R)-3-halogeno-1,2-propanediol with trimethylamine, with a halogenating reagent. According to the present invention, 3-halogeno-2-hydroxypropyltrimethylammonium halide or one having the (S)-configuration, which is a useful intermediate for the synthesis of carnitine or especially (l)-carnitine, can be obtained economically, efficiently and easily.
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- Process for preparing L-carnitine and salts thereof
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L-carnitine and salts thereof are resolved from DL-carnitine by the use as a resolving agent of dibenzoyl-L(+)tartaric acid. L-carnitine is known as vitamin BT and is useful as a medicine.
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- ON THE STERIC COURSE OF BAKER' S YEAST MEDIATED REDUCTION OF ALKYL 4-AZIDO-AND 4-BROMO-3-OXOBUTYRATE. SYNTHESIS OF (R)- AND (S)-CARNITIN
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Baker's yeast reduction of ethyl 4-azido-and 4-bromo-3-oxobutyrate affords (3R) (8) and (3S) (2), respectively, in high optical purity.
- Fuganti, Claudio,Grasselli, Piero
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p. 101 - 104
(2007/10/02)
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- Carnitinamides of optically active aminoacids
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Amides of carnitine or acyl-carnitines having general formula: STR1 wherein X- is a halogen anion, e.g. the chloride anion R is either hydrogen or an acyl radical, such as acetyl, propionyl or butyryl; and Y is the residue of an optically active esterified amino-acid (e.g. the residue of L-phenylglycine methyl ester, STR2 are prepared by either (a) directly condensing D,L-carnitine (or acyl-D,L-carnitine) with an ester of an optically active aminoacid, or (b) preparing the acid halogenide of D,L-carnitine or acyl-D,L-carnitine and subsequently condensing it with an ester of an optically active aminoacid. The mixture of the diastereoisomer amides thus obtained is resolved by fractional crystallization from organic solvents into the respective separated diastereoisomers. These optically active amides are useful therapeutic agents for treating cardiac disorders, hyperlipidaemias and hyperlipoproteinaemias and, furthermore, can be hydrolyzed with procedures known per se into L-carnitine and D-carnitine, respectively.
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- Process for the production of carnitine
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The process for the production of carnitine hydrochloride which involves placing an ester of γ-halo-acetoacetic acid having the formula: STR1 wherein R1 is hydrogen, R2 is a lower alkyl group having 1 to 10 carbon atoms and X is a halogen atom selected from the group consisting of chlorine or bromine, in an aqueous solution of excess trimethyl amine held at a temperature between 0° and 50° C., a reaction resulting between said ester and said amine. The excess trimethyl amine is distilled off. The pH of the solution is adjusted between 4 and 8, (3-carbalkoxy-2-oxopropyl)-trimethyl ammonium halide resulting. The (3-carbalkoxy-2-oxopropyl)-trimethyl ammonium is hydrogenated without isolating said halide from solution, a carnitine ester resulting. The carnitine ester is converted by means of aqueous hydrochloric acid into carnitine hydrochloride.
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