cas 541-15-1, L-carnitine | Articles data

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Preparation method of L-carnitine
The invention relates to the technical field of organic synthesis, in particular to a preparation method of L-carnitine, which comprises the following steps: by taking R-4-chloro-3-hydroxybutyrate as a raw material, carrying out catalytic cyclization under an alkaline condition to generate (2R)-2-ethylene oxide ethyl acetate, and carrying out ring-opening reaction with trimethylamine to obtain the L-carnitine. According to the invention, the technical scheme of first cyclization and then ring opening is adopted, so that the step of removing halide ions in ion exchange resin is avoided, byproducts such as sodium chloride and the like are convenient to remove, and the production cost is reduced; the method is simple to operate, low in production cost, high in target product purity, high in yield and suitable for being applied to industrial production.
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Paragraph 0034; -0035; 0038-0040; 0051

(2021/12/07)

Shedding light on the mitochondrial matrix through a functional membrane transporter
The first fluorescent probes that are actively channeled into the mitochondrial matrix by a specific mitochondrial membrane transporter in living cells have been developed. The new functional probes (BCT) have a minimalist structural design based on the highly efficient and photostable BODIPY chromophore and carnitine as a biotargeting element. Both units are orthogonally bonded through the common boron atom, thus avoiding the use of complex polyatomic connectors. In contrast to known mitochondria-specific dyes, BCTs selectively label these organelles regardless of their transmembrane potential and in an enantioselective way. The obtained experimental evidence supports carnitine-acylcarnitine translocase (CACT) as the key transporter protein for BCTs, which behave therefore as acylcarnitine biomimetics. This simple structural design can be readily extended to other structurally diverse starting F-BODIPYs to obtain BCTs with varied emission wavelengths along the visible and NIR spectral regions and with multifunctional capabilities. BCTs are the first fluorescent derivatives of carnitine to be used in cell microscopy and stand as promising research tools to explore the role of the carnitine shuttle system in cancer and metabolic diseases. Extension of this approach to other small-molecule mitochondrial transporters is envisaged.
Blázquez-Moraleja, Alberto,Sáenz-De-Santa María, Ines,Chiara, María D.,álvarez-Fernández, Delia,García-Moreno, Inmaculada,Prieto-Montero, Ruth,Martínez-Martínez, Virginia,López Arbeloa, I?igo,Chiara, Jose Luis
p. 1052 - 1065
(2020/02/11)

Micro-reaction continuous flow synthesis method of levocarnitine
The invention provides a micro-reaction continuous flow synthesis method of levocarnitine. An existing preparation method has the defects of complicated operation, long reaction time, low yield and the like. According to the method, (R)-4-halogenated-3-hydroxybutyrate and trimethylamine are continuously subjected to quaternization and hydrolysis reaction in a micro-channel reactor in the presenceof an alkali to prepare the levocarnitine. The reaction time of the method is only several minutes, the yield is high, the technological process is easy and convenient to operate, and industrial production is easy.
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Paragraph 0042-0064

(2020/09/08)

Preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as starting material
The invention discloses a preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as a starting material, and belongs to the field of medicinal chemistry. The method comprises the steps: using R-(-)-epoxychlorohydrin and hydrocyanic acid as starting materials, performing a reaction for synthesis of R-4-chloro-3-hydroxybutyronitrile under the action of a basic catalyst, thensynthesizing L-carnitine hydrochloride through two routes, purifying the L-carnitine hydrochloride prepared through the two routes further through resin so as to remove chloride ions, and preparing the final product L-carnitine. The two process routes are simple, the reaction conditions are mild, the operation is simple and feasible, and industrial production is convenient; the whole process is green and environmentally friendly, the reaction yield is high, three waste is little, no sodium cyanide is used, and no solid waste sodium salt is generated; and the hydrolysis by-product ammonium chloride has good quality, and can be sold as a by-product, and great economic benefits and market competitiveness are achieved.
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Paragraph 0078-0093

(2019/11/12)

Asymmetric synthesis method of L-carnitine
The invention relates to an asymmetric synthesis method of L-carnitine. Acetyl chloride (II) generates ketene in situ at a low temperature under the catalysis of organic base, the ketene and 2-chloroacetaldehyde (I) are directly subjected to an asymmetric intermolecular [2+2] cycloaddition reaction without separation in the presence of Lewis acid and a chiral catalyst to obtain chiral lactone, andlactone (IV) is reacted with a trimethylamine solution to obtain L-carnitine with high enantioselectivity. The synthetic method is simple, the yield of asymmetric catalytic products is high, the enantioselectivity of lactone products is 95% or above, conditions are mild, operation is easy, the production cost is low, and the method can be used for industrial production.
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Page/Page column 4-9

(2019/12/02)

A New Microbial Pathway for Organophosphonate Degradation Catalyzed by Two Previously Misannotated Non-Heme-Iron Oxygenases
The assignment of biochemical functions to hypothetical proteins is challenged by functional diversification within many protein structural superfamilies. This diversification, which is particularly common for metalloenzymes, renders functional annotations that are founded solely on sequence and domain similarities unreliable and often erroneous. Definitive biochemical characterization to delineate functional subgroups within these superfamilies will aid in improving bioinformatic approaches for functional annotation. We describe here the structural and functional characterization of two non-heme-iron oxygenases, TmpA and TmpB, which are encoded by a genomically clustered pair of genes found in more than 350 species of bacteria. TmpA and TmpB are functional homologues of a pair of enzymes (PhnY and PhnZ) that degrade 2-aminoethylphosphonate but instead act on its naturally occurring, quaternary ammonium analogue, 2-(trimethylammonio)ethylphosphonate (TMAEP). TmpA, an iron(II)- and 2-(oxo)glutarate-dependent oxygenase misannotated as a γ-butyrobetaine (γbb) hydroxylase, shows no activity toward γbb but efficiently hydroxylates TMAEP. The product, (R)-1-hydroxy-2-(trimethylammonio)ethylphosphonate [(R)-OH-TMAEP], then serves as the substrate for the second enzyme, TmpB. By contrast to its purported phosphohydrolytic activity, TmpB is an HD-domain oxygenase that uses a mixed-valent diiron cofactor to enact oxidative cleavage of the C-P bond of its substrate, yielding glycine betaine and phosphate. The high specificities of TmpA and TmpB for their N-trimethylated substrates suggest that they have evolved specifically to degrade TMAEP, which was not previously known to be subject to microbial catabolism. This study thus adds to the growing list of known pathways through which microbes break down organophosphonates to harvest phosphorus, carbon, and nitrogen in nutrient-limited niches.
Rajakovich, Lauren J.,Pandelia, Maria-Eirini,Mitchell, Andrew J.,Chang, Wei-Chen,Zhang, Bo,Boal, Amie K.,Krebs, Carsten,Bollinger, J. Martin
p. 1627 - 1647
(2019/03/19)

Synthesis method of quaternary amine inner salt
The invention discloses a synthesis method of quaternary amine inner salt. The synthesis method comprises the following steps: (a) reduction reaction: taking a compound having a structure shown as theformula I as a raw material, carrying out a reduction reaction among the compound, an apoenzyme, a dehydrogenase and a coenzyme in monosaccharide within a certain pH range, removing enzymes with active carbon and performing rectification, so as to obtain a reduced product shown in the original specification, wherein X represents one of chlorine, bromine and iodine in halogens, and R represents one of a saturated alkyl or an unsaturated alkyl; (b) synthesis of the quaternary amine inner salt: carrying out a reaction between an obtained product and trimethylamine under a strong base condition to obtain quaternary amine hydrochloride, exchanging the quaternary amine hydrochloride in ion exchange resin to remove halide ions, performing concentration and refining a concentrated product with alcohol and acetone, so as to obtain the quaternary amine inner salt. The synthesis method has the advantages of being high in yield in each step, simple to operate and mild in reaction conditions, effectively removing enzyme residues by introducing a chiral structure with a high-selectivity enzymatic method, avoiding a reagent with high toxicity and high pollution by utilizing renewable resin for desalting, obtaining the high-purity product, being suitable for industrial production and the like.
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Paragraph 0080; 0081

(2019/01/14)

METHODS AND COMPOSITIONS RELATING TO CARNITINE- DERIVED MATERIALS
Zwitterionic monomers, camitine-derived zwitterionic polymers, carnitine ester cationic monomers, carnitine ester cationic polymers, conjugate compositions including a carnitine-derived zwitterionic polymer, and related compositions' and methods are provided which have various uses including as coatings, pharmaceuticals, diagnostics, encapsulation materials, and antifouling materials, among other utilities.
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Paragraph 00204-00205

(2019/01/05)

A low-cost high-safety L - carnitine preparation method (by machine translation)
The invention relates to a kind of vitamin nutrient preparation method, in particular to a low-cost high-safety L - carnitine preparation method. It is to solve the problems of the prior art L - carnitine preparation of unstable product quality, the use of highly toxic chemicals cyanide, in production had a certain amount of risk, and the production cost is higher. The present invention is added in the high-pressure reactor chloro acetyl ethyl acetate and anhydrous ethanol, access trimethylamine gas, and then adding the compound (III), catalyst and methanol times, stir for three times after hydrogen replacement, recovery of catalyst, filtering to obtain the compound (II), in the reactor, (II) compound is added and the sodium hydroxide solution, then stirring under heating to reflux the reaction, after the reaction, to obtain the L - carnitine crude alkali solution, through the cation exchange resin treatment to remove impurities, to obtain an aqueous solution of L - carnitine, concentrated, vacuum drying to obtain L - carnitine (I) works. (by machine translation)
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Paragraph 0023; 0025; 0030; 0031; 0041; 0043; 0045

(2018/07/30)

Novel method for preparing L-carnitine
The invention discloses a novel method for preparing L-carnitine and belongs to the technical field of medication chemistry. The method disclosed by the invention comprises the following steps: reacting quinine I and trimethylchlorosilane, thereby obtaining a quinine derivative II; reacting the quinine derivative II with racemic epoxy chloropropane, thereby obtaining quinine derivative quaternary ammonium salt III; reacting the quinine derivative quaternary ammonium salt III with a cyanide inorganic salt, and performing chiral ring opening to generate (R)-2-hydroxynitrile quaternary ammonium salt IV; carrying out an ion exchange reaction between the (R)-2-hydroxynitrile quaternary ammonium salt IV and trimethylamine, thereby obtaining (R)-2-hydroxynitrile trimethylamine salt, performing acidic hydrolysis, and performing ion exchange desalination, thereby obtaining the L-carnitine. The method provided by the invention is simple and feasible, the yield is greatly improved, and residues of heavy metal ions are avoided.
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Paragraph 0021

(2017/08/27)

Preparation method of levocarnitine
The invention provides a preparation method of levocarnitine. The preparation method comprises the following steps: taking epoxy chloropropane as a starting material, then carrying out amination, cyaniding and carrying out ester exchange under the action of lipase CALB to obtain corresponding chiral ester, then carrying out alkaline hydrolysis and acidification, and then removing chlorine ions under the action of strongly alkaline resin, so that the levocarnitine finished product is obtained. In the invention, acid resin is used in an ester exchange process, and recemization can be realized, so that yield and optical purity of the levocarnitine are improved.
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(2017/08/29)

A preparation method of the compound-carnitine
The invention discloses a preparation method of a levocarnitine compound, and the preparation method is applied to the technical field of pharmaceutical chemical synthesis. The preparation method comprises the following steps that (1), 4-chloroacetoacetic acid ethyl ester serves as the initial raw material, under the condition that a solvent exists, an asymmetric catalyst phosphine ligand ruthenium complex is applied for hydrogenation reduction, and (R)-4-chlorine-3-hydroxybutyrate ethyl ester is obtained by vacuum concentration and high vacuum distillation; (2), a trimethylamine squeous solution and the (R)-4-chlorine-3-hydroxybutyrate ethyl ester are added dropwise and slowly in the solvent comprising inorganic base, the dropping speed is controlled, low temperature reaction is carried out, then indoor temperature reaction is carried out, the pH of the mixture is adjusted to be 6 through concentrated hydrochloric acid after reaction is finished, and the levocarnitine compound is obtained by resin column purification. According to the method, the asymmetric catalytic reaction is applied, the two-step reaction that an optical active intermediate with high optical purity and high yield can be obtained and the optical active intermediate is converted to be the levocarnitine compound is the one-pot reaction, the water serves as the reaction solvent, the inorganic base is used for catalysis, the unique process of indoor temperature reaction is adopted, the product quality is good, the purity is high, the yield can reach up to 80%, the reaction steps of the preparation method are short, operation is easy, pollution to environment is small, and green resources are protected.
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Paragraph 0031-0033

(2017/04/03)

Asymmetric cycloetherifications by bifunctional aminothiourea catalysts: The importance of hydrogen bonding
Chiral oxacyclic frameworks are prevalent in many natural products and bioactive compounds. In addition, a number of them are important synthetic intermediates. Thus, the synthesis of such structures is a significant goal in the field of organic chemistry. However, the development of catalytic asymmetric cycloetherification for the straightforward synthesis of these compounds remains a challenge. In this study, we propose the use of aminothiourea catalysis as an effective way to accomplish such a challenge. The asymmetric synthesis of chiral oxygen heterocycles, including tetrahydrofurans, tetrahydropyrans, and 1,3-dioxolanes, is demonstrated herein using intramolecular oxy-Michael addition mediated by bifunctional aminothiourea catalysts. Georg Thieme Verlag Stuttgart · New York.
Fukata, Yukihiro,Miyaji, Ryota,Okamura, Takaaki,Asano, Keisuke,Matsubara, Seijiro
p. 1627 - 1634
(2013/07/27)

PROCESS FOR THE PRODUCTION OF CARNITINE BY CYCLOADDITION
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)

Use of L-Carnitine, salts and derivatives thereof for reducing or preventing fatigue and improving cognitive function
The invention relates to the use of L-carnitine, a salt of L-carnitine, a derivative of L-carnitine and/or salt of a derivative of L-carnitine, as well as respective methods and compositions, for reducing or preventing fatigue and/or for improving cognitive function in an animal. The animal is preferably a healthy individual and the use is preferably a non-therapeutic use.
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(2012/10/18)

Organocatalytic asymmetric oxy-Michael addition to a γ-hydroxy- α,β-unsaturated thioester via hemiacetal intermediates
We report an asymmetric oxy-Michael addition to a γ-hydroxy-α, β-unsaturated thioester via hemiacetal intermediates in the presence of Cinchona-alkaloid-thiourea-based bifunctional organocatalysts. This method provides a novel enantioselective route to β-hydroxy carboxyl compounds, which in turn can be used to synthesize valuable chiral building blocks.
Okamura, Takaaki,Asano, Keisuke,Matsubara, Seijiro
supporting information; experimental part
p. 5076 - 5078
(2012/07/02)

PROCESS FOR THE PRODUCTION OF CARNITINE FROM BETA-LACTONES
The invention relates to a method for the production of L-carnitine, wherein a β-lactone, which is a 4-(halomethyl)oxetane-2-one, is converted into carnitine with trimethylamine (TMA), wherein the β-lactone is not subjected to a basic hydrolysis step before being contacted with the trimethylamine. The invention also relates to a carnitine having a unique impurity profile.
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Page/Page column 6

(2012/02/03)

A PREPARATION METHOD OF HIGH-PURITY L-CARNITINE
The present invention relate to a preparation method of high-purity L-carnitine which belongs to an important technique of qulity control in different steps of chiral medicine production. The method comprises the following steps of :monitoring the content of the L-isomer impurity in chiral material S-epichlorohydrin by gas chromatography and chiral cilumn and controlling the content of the L-isomer impurity in chiral raw material in the definite range; monitoring and controlling the specific optical rotation of the chiral intermediate L-3-chloro-2-hydroxy-N,N,N-trimethyl-propanaminium in the definite ranges using a polarimeter; monitoring the content of the R-isomer in the intermediate L-3-cyano-2-hydroxy-N,N,N-trimethyl-propanaminium using derivation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC and controlling the content of the isomer in the intermediate in the definite range; and measuring the final product L-carnitine using derviation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC. This method gives the high-purity L-carnitine in which the content of L-isomer may be more than 97% and that of R-isomer less than 2%.
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Page/Page column 8-9

(2011/09/15)

PREPARATION METHOD OF HIGH-PURITY L-CARNITINE
The present invention relate to a preparation method of high-purity L-carnitine which belongs to an important technique of quality control in different steps of chiral medicine production. The method comprises the following steps of: monitoring the content of the L-isomer impurity in chiral material S-epichlorohydrin by gas chromatography and chiral column and controlling the content of the L-isomer impurity in chiral raw material in the definite range; monitoring and controlling the specific optical rotation of the chiral intermediate L-3-chloro-2-hydroxy-N,N,N-trimethyl-propanaminium in the definite ranges using a polarimeter; monitoring the content of the R-isomer in the intermediate L-3-cyano-2-hydroxy-N,N,N-trimethyl-propanaminium using derivation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC and controlling the content of the isomer in the intermediate in the definite range; and measuring the final product L-carnitine using derviation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC. This method gives the high-purity L-carnitine in which the content of L-isomer may be more than 97% and that of R-isomerless than 2%.
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Page/Page column 5

(2011/11/06)

Asymmetric synthesis of l-carnitine from (R)-3-chloro-1,2-propanediol
A practical chemical synthesis of l-carnitine (1) has been accomplished from (R)-3-chloro-1,2-propanediol ((R)-4), which is a main by-product originated from (R,R)-Salen Co(III) catalyzed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin. (R)-4 was utilized as a chiral starting material to prepare the key intermediate cyclic sulfite ((R)-5). The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of bioactive compounds.
Li, Xu Qin,Yang, Yun Xu,Wang, Wei Li,Hu, Bin,Xue, Hui Min,Zhang, Tian Yi,Zhang, Xue Tao
body text
p. 765 - 767
(2012/01/03)

Methods for the production of l-carnitine
Subject of the invention is a method for the production of L-carnitine, comprising the steps of (a) providing a solution comprising at least 5% (w/w) carnitine in a first solvent, wherein the carnitine is a mixture of D- and L-carnitine, (b) optionally seeding the solution with L-carnitine crystals, (c) adding an second solvent, in which the L-carnitine is not soluble or has a low solubility, (d) isolating crystals comprising L-carnitine.
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Page/Page column 5

(2011/06/24)

METHODS FOR THE PRODUCTION OF L-CARNITINE
Subject of the invention is a method for the production of L-carnitine, comprising the steps of (a) providing a solution comprising at least 5% (w/w) carnitine in a first solvent, wherein the carnitine is a mixture of D- and L-carnitine,(b) optionally seeding the solution with L-carnitine crystals,(c) adding an second solvent, in which the L-carnitine is not soluble or has a low solubility,(d) isolating crystals comprising L-carnitine.
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Page/Page column 3

(2011/06/10)

Crystal structure of human gamma-butyrobetaine hydroxylase
Gamma-butyrobetaine hydroxylase (GBBH) is a 2-ketoglutarate-dependent dioxygenase that catalyzes the biosynthesis of l-carnitine by hydroxylation of gamma-butyrobetaine (GBB). l-carnitine is required for the transport of long-chain fatty acids into mitochondria for generating metabolic energy. The only known synthetic inhibitor of GBBH is mildronate (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), which is a non-hydroxylatable analog of GBB.To aid in the discovery of novel GBBH inhibitors by rational drug design, we have solved the three-dimensional structure of recombinant human GBBH at 2.0. ? resolution. The GBBH monomer consists of a catalytic double-stranded β-helix (DBSH) domain, which is found in all 2KG oxygenases, and a smaller N-terminal domain. Extensive interactions between two monomers confirm earlier observations that GBBH is dimeric in its biological state. Although many 2KG oxygenases are multimeric, the dimerization interface of GBBH is very different from that of related enzymes.The N-terminal domain of GBBH has a similar fold to the DUF971 superfamily, which consists of several short bacterial proteins with unknown function. The N-terminal domain has a bound Zn ion, which is coordinated by three cysteines and one histidine. Although several other 2KG oxygenases with known structures have more than one domain, none of them resemble the N-terminal domain of GBBH. The N-terminal domain may facilitate dimer formation, but its precise biological role remains to be discovered.The active site of the catalytic domain of GBBH is similar to that of other 2KG oxygenases, and Fe(II)-binding residues form a conserved His-X-Asp-X. n-His triad, which is found in all related enzymes.
Tars, Kaspars,Rumnieks, Janis,Zeltins, Andris,Kazaks, Andris,Kotelovica, Svetlana,Leonciks, Ainars,Sharipo, Jelena,Viksna, Arturs,Kuka, Janis,Liepinsh, Edgars,Dambrova, Maija
experimental part
p. 634 - 639
(2011/10/13)

PROCESS FOR PRODUCTION OF BETAINE
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 25

(2009/09/26)

PROCESS FOR THE PREPARATION OF BETAINES
Betaines of formula R3N+-Q-COO- (I), wherein R is C1-4 alkyl and Q is C1-4 alkanediyl, optionally substituted with hydroxy, are prepared in one step by adding an ω-halocarboxylate of formula X-Q-COOR' (II), wherein Q is as defined above, R' is C11-4 alkyl and X is chlorine, bromine or iodine, to an aqueous solution containing a tertiary amine of formula R3N (III), Wherein R is as defined above and a base selected from alkali hydroxides and alkaline earth hydroxides. The process is particularly suited to the production of L-carnitine.
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Page/Page column 3-5

(2009/06/27)

PROCESS FOR L-CARNITINE
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.
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Page/Page column 6

(2008/06/13)

Lipase-catalyzed enantiomer separation of 3-hydroxy-4-(tosyloxy) butanenitrile: Synthesis of (R)-GABOB (=(3R)-4-amino-3-hydroxybutanoic acid) and (R)-carnitine hydrochloride (= (2R)-3-carboxy-2-hydroxy-N,N,N-trimethylpropan- 1-aminium chloride)
Enzymatic resolution of racemic 3-hydroxy-4-(tosyloxy)butanenitrile ((±)-5) by using various lipases in different solvents were studied. The obtained optically pure (3R)-3-(acetyloxy)-4-(tosyloxy)-butanenitrile ((R)-6), upon treatment with aqueous ammonia followed by cone. HCl solution, provided (R)-GABOB (=(3R)-4-amino-3-hydroxybutanoic acid; (R)-1). Similarly, reaction of (R)-6 with aqueous trimethylamine solution followed by cone. HCl solution provided (R)-carnitine hydrochloride (=(2R)-3-carboxy-2-hydroxy-N,N,N- trimethylpropan-1-aminium chloride; (R)-2·HCl) in an expeditious manner.
Kamal, Ahmed,Khanna, G. B. Ramesh,Krishnaji, Tadiparthi
p. 1723 - 1730
(2008/03/12)

METHOD OF RECOVERING CARNITINE
A method of recovering carnitine in the state of being low in the content of cations, such as calcium, from milk or other dairy products. There is provided a method of recovering carnitine characterized by including feeding an ultrafiltrate, or whey, of milk or other dairy products into a column packed with a cation exchange resin from the top thereof; discontinuing the feeding when carnitine adsorption has occurred in an underlayer part of lower about 1/3 of resin packed portion of the column; and thereafter supplying an elution liquid to only the underlayer part so as to elute carnitine.
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Page/Page column 7-16; 1/6-6/6

(2008/06/13)

PROCESS FOR L-CARNITINE AND ACETYL L-CARNITINE HYDROCHLORIDE
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.
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Page/Page column 9

(2010/11/29)

An efficient, highly enantioenriched route to L-carnitine and α-lipoic acid via hydrolytic kinetic resolution
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
p. 1863 - 1867
(2008/01/27)

Process for preparing R-(-) -carnitine from S-(-)-chlorosuccinic acid or from a derivative thereof
An inner salt of L-carnitine is prepared by reduction, with a suitable reducing agent, of a compound of formula (I): where X1and X2, which may be the same or different, are hydroxy, C1-C4alkoxy, phenoxy, halogen, or X1and X2, when taken together are an oxygen atom and the resulting compound is a derivative of succinic anhydride; Y is halogen, the mesyloxy or the tosyloxy group: and subsequent treatment with water, then with a base and then with trimethylamine.
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Page column 12

(2008/06/13)

Stereospecific hydrolysis of optically active esters
A new, more efficient and highly stereospecific process is described for the preparation of compounds with general formula (R)-(I) and of absolute configuration (R), where the groups M, W, Q and Q1 are as defined in the description, starting from compounds of absolute configuration (S) by hydrolysis, in the presence of acids, of the corresponding esterified derivatives. The (R)-(I) products obtained with the process described herein are chiral synthons useful for the production of enanthiomerically pure drugs. The preparation of (R)-carnitine is also provided.
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(2008/06/13)

Double salts of fumaric acid with a carnitine and an amino acid and food supplements, dietary supplements and drugs containing same
Double fumarates of L-carnitine or isovaleryl L-carnitine and an amino acid are disclosed which are useful as active ingredients of food supplements, dietary supplements or drugs.
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(2008/06/13)

Nitriloxy derivatives of (R) and (S)-carnitine
Carnitine derivatives of formula (I) are described in racemic and/or optically active form, as well as the process for their preparation and their use as pharmaceutical anti-angina active ingredients for the treatment of ischaemic heart disease. Also described is a process for producing the (R)-carnitine enantiomer from (S)-carnitine (or vice versa), using the derivatives of formula (I).
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Page column 7-8

(2008/06/13)

Process for the preparation of L-carnitine
A process for the preparation of L-carnitine using (S)-3-activated hydroxybutyrolactone as a raw material, which is subject to a ring-opening reaction, expoxydation where the chiral center is inversely converted, and nucleophilic substitution of trimethylamine.
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Example 2

(2008/06/13)

Retention and selectivity of teicoplanin stationary phases after copper complexation and isotopic exchange
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
p. 5499 - 5508
(2007/10/03)

Asymmetric synthesis of (S)-(+)-carnitine and analogs
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
p. 6505 - 6509
(2007/10/03)

Asymmetric synthesis of (R)-(-)-carnitine
A TiCl4-promoted Mukaiyama-type aldol reaction of the ketenesilyl acetal of ethyl acetate with the lactone carbonyl of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin- 2-one (1) proceeds with a high degree of diastereoselectivity. The TBDMS-protected hemiketal thus obtained was efficiently converted into highly enantiomerically enriched (R)-(-)-carnitine by following an elimination-reduction protocol. This approach further demonstrates the utility of commercially available glycine template 1 as a potential substrate for the asymmetric synthesis of both enantiomers of carnitine.
Jain, Rajendra P.,Williams, Robert M.
p. 4437 - 4440
(2007/10/03)

Nitriloxy derivatives of (R) and (S)-carnitine
New camitine derivatives of general formula (I) are described in racemic and/or optically active form, as well as the process for their preparation and their use as pharmaceutical anti-angina active ingredients for the treatment of ischaemic heart disease. A further subject of the invention described herein is a process for producing the (R)-camitine enantiomer from (S)-carnitine (or vice versa), through the use of derivatives of general formula (I).
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(2008/06/13)

Efficient Enantioselective Synthesis of (R)-(-)-Carnitine from Glycerol
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Marzi, Mauro,Minetti, Patrizia,Moretti, Giampiero,Tinti, Maria Ornella,De Angelis, Francesco
p. 6766 - 6769
(2007/10/03)

Parenteral nutrition therapy with amino acids
Parenteral nutrition aqueous solutions are provided which preferably contain glutamine together with other organic nitrogen containing compounds. The respective concentrations of the compounds present in any given such solution are typically approximately multiples of the concentration of the same compounds as found in normal human plasma, and the respective mole ratios of various such compounds in any given such solution relative to one another are approximately the same mole ratio associated with the same compounds as found in normal human plasma. Processes for using such solutions are provided.
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(2008/06/13)

A convenient synthesis of R-(-)-carnitine from R-(-)-epichlorohydrin
A convenient four-step synthesis of R-(-)-carnitine (1) is described from the reaction of R-(-)-epichlorohydrin (2) with vinylmagnesium bromide followed by formation of the ammonium salt 4 with trimethylamine and finally ozonolysis of the corresponding ammonium hydroxide 5.
Kabat, Marek M.,Daniewski, Andrzej R.,Burger, Walter
p. 2663 - 2665
(2007/10/03)

Phosphinyloxy propanaminium inner salt derivatives
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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(2008/06/13)

The β-Lactone Route to a Totally Stereoselective Synthesis of Carnitine Derivatives
The syntheses of the enantiomerically pure, carnitine-related β-lactones 10 and 12 starting from various carnitine precursors of opposite configuration (or carnitine itself) are described. (R)-3-Chlorocarnitine (20) has also been directly prepared from (S)-carnitine (14) and has been cyclized to 12 by a second inversion of configuration of the stereogenic centre.By nucleophilic attack at the carbonyl carbon, the β-lactone carnitine derivatives have been converted into esters, amides, and guanidino congeners.Following this route, it is possible to obtain the biologically active isomer (R)-carnitine (1) starting from the otherwise useless industrial by-product (S)-carnitine (14).Nucleophilic attack by selected ambident nucleophiles at the β-carbon of the same β-lactone derivatives results in a second inversion of configuration of the stereogenic centre.Besides aminocarnitine (3), chiral acetylcarnitine (2) and acetylthiocarnitine (5) have been synthesized in homochiral forms following this latter procedure. - Keywords: asymmetric ring-opening; carnitine; cyclizations; β-lactones; nucleophilic substitutions
Bernabei, Ida,Castagnani, Roberto,Angelis, Francesco De,Fusco, Enrico De,Gianessi, Fabio,et al.
p. 826 - 831
(2007/10/03)

Efficient asymmetric hydrogenation of α-amino ketone derivatives. A highly enantioselective synthesis of phenylephrine, levamisole, carnitine and propranolol
The complexes of pyrrolidine bisphosphine ligands (CPMs) with rhodium (I) were found to be efficient catalysts for asymmetric hydrogenation of α-amino ketone hydrochloride derivatives. Utilizing this methodology, we have developed efficient asymmetric syntheses of the optically active β-amino alcohols, phenylephrine, levamisole, carnitine and propranolol.
Sukuraba,Takahashi,Takeda,Achiwa
p. 738 - 747
(2007/10/02)

Process for preparing phosphinyloxy propanaminium inner salt derivatives
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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(2008/06/13)

Process for manufacturing L-(-)-carnitine from a waste product having opposite configuration
The present invention relates to a proces for manufacturing L-(-)-carnitine from D-(+)-carnitine or a derivative thereof. D-(+)-carnitine is esterified in order to protect the carboxyl group and subsequently converted to an acyl derivative. The acyl derivative is then converted to a lactone of L-(-)-carnitine. Finally, the lactone is reopened to obtain L-(-)-carnitine.
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(2008/06/13)

Vollstaendig enantioselektive Inversion der Konfiguration von (S)-(+)-Carnitinen
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Bernabei, Ida,Castagnani, Roberto,Angelis, Francesco De,Witt Scalfaro, Paolo De,Giannessi, Fabio,et al.
p. 2202 - 2203
(2007/10/02)

Process for manufacturing L-(-)-carnitine from a waste product having opposite configuration
The present invention relates to a proces for manufacturing L-(-)-carnitine from D-(+)-carnitine or a derivative thereof. D-(+)-carnitine is esterified in order to protect the carboxyl group and subsequently converted to an acyl derivative. The acyl derivative is then converted to a lactone of L-(-)-carnitine. Finally, the lactone is reopened to obtain L-(-)-carnitine.
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(2008/06/13)

Improved process for manufacturing L-(-)-carnitine from waste products having opposite configuration
A process for preparing L-(-)-carnitine is disclosed which comprises acylating D-(+)-carnitinenitrile or D-(+)-carnitinamide to their respective acylderivatives which via acid hydrolysis yield D-(+)-carnitine which is converted to the lactone of L-(-)-carnitine. The lactone in a basic environment yields L-(-)-carnitine inner salt.
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(2008/06/13)