- Peptide Metal-Organic Frameworks for Enantioselective Separation of Chiral Drugs
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We report the use of a chiral Cu(II) 3D metal-organic framework (MOF) based on the tripeptide Gly-l-His-Gly (GHG) for the enantioselective separation of metamphetamine and ephedrine. Monte Carlo simulations suggest that chiral recognition is linked to preferential binding of one of the enantiomers as a result of either stronger or additional H-bonds with the framework that lead to energetically more stable diastereomeric adducts. Solid-phase extraction of a racemic mixture by using Cu(GHG) as the extractive phase permits isolating >50% of the (+)-ephedrine enantiomer as target compound in only 4 min. To our knowledge, this represents the first example of a MOF capable of separating chiral polar drugs.
- Navarro-Sánchez, José,Argente-García, Ana I.,Moliner-Martínez, Yolanda,Roca-Sanjuán, Daniel,Antypov, Dmytro,Campíns-Falcó, Pilar,Rosseinsky, Matthew J.,Martí-Gastaldo, Carlos
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Read Online
- Process for preparing beta-aminoalcohol from terminal olefin
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The invention provides a method for preparing beta-aminoalcohol from terminal olefin. The method comprises the following steps: with the terminal olefin as a raw material, adding dibromohydantoin, conducting stirring, and then adding organic amine to obtain corresponding beta-aminoalcohol. The method has the advantages of mild conditions, easy operation, cheap raw materials, and wide application prospect.
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Paragraph 0031; 0032; 0048
(2020/06/17)
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- BIOCATALYTICAL PROCESS FOR RACEMIZATION OF D-EPHEDRINE
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This invention relates to methods for racemization of dextro-rotatory ephedrine via enzymatic kinetic conversion, and is particularly useful for conversion of dextro- rotatory ephedrine (d- ephedrine) to racemic mixture of dextro-rotatory ephedrine (d-ephedrine) and levo-rotatory ephedrine (l-ephedrine) to recover the levo-rotatory ephedrine that exhibit potential bronchodilatory and anti-hypotensive activities. The process provides a suspension of Rhizopus Oryzae fungi pellets in diammonium phosphate buffer having pH in the range of pH 5 to 9 and effective sonication to extract specific enzymes for inversion of functional groups present on the chiral carbon atom of d-ephedrine molecule at low temperature which has advantages of working at lower temperature range (20 to 50 °C), lower energy consumption, lesser formation of by-products.
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Page/Page column 13; 14
(2020/05/28)
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- Peroxygenase-Catalysed Epoxidation of Styrene Derivatives in Neat Reaction Media
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Biocatalytic oxyfunctionalisation reactions are traditionally conducted in aqueous media limiting their production yield. Here we report the application of a peroxygenase in neat reaction conditions reaching product concentrations of up to 360 mM.
- Alcalde, Miguel,Arends, Isabel W. C. E.,Hollmann, Frank,Paul, Caroline E.,Rauch, Marine C. R.,Tieves, Florian
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- Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
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A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.
- Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
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p. 1067 - 1078
(2018/08/01)
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- A short enantioselective synthesis of ephedrine, amphetamine and their analogues via two stereocentered Co(III)-catalyzed hydrolytic kinetic resolution of racemic syn-benzyloxy epoxide
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An efficient route for the synthesis of 6 drugs belonging to phenethylamine and amphetamine classes in excellent overall yields and high optical purity has been described. The strategy involves introduction of stereogenic centers by means of two-stereocentered Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of racemic syn-benzyloxy epoxide followed by Pd-catalyzed regioselective cationic hydrogenation of amino alcohols as the key reactions.
- Lalwani, Komal G.,Sudalai, Arumugam
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supporting information
p. 6488 - 6490
(2015/11/16)
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- PROCESSES AND INTERMEDIATES FOR PREPARING A MACROCYCLIC PROTEASE INHIBITOR OF HCV
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A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-(-)- ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-(-)-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-(-)-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis- (1R,2S)-(-)-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-(-)-ephedrine from the precipitated salt obtained in step (b).
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Page/Page column 21-22
(2011/10/10)
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- Composition and stereochemistry of ephedrine alkaloids accumulation in Ephedra sinica Stapf
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Ephedra sinica Stapf (Ephedraceae) is a widely used Chinese medicinal plant (Chinese name: Ma Huang). The main active constituents of E. sinica are the unique and taxonomically restricted adrenergic agonists phenylpropylamino alkaloids, also known as ephedrine alkaloids: (1R,2S)-norephedrine (1S,2S)-norpseudoephedrine, (1R,2S)-ephedrine, (1S,2S)-pseudoephedrine, (1R,2S)-N-methylephedrine and (1S,2S)-N-methylpseudoephedrine. GC-MS analysis of freshly picked young E. sinica stems enabled the detection of 1-phenylpropane-1,2-dione and (S)-cathinone, the first two putative committed biosynthetic precursors to the ephedrine alkaloids. These metabolites are only present in young E. sinica stems and not in mature stems or roots. The related Ephedra foemina and Ephedra foliata also lack ephedrine alkaloids and their metabolic precursors in their aerial parts. A marked diversity in the ephedrine alkaloids content and stereochemical composition in 16 different E. sinica accessions growing under the same environmental conditions was revealed, indicating genetic control of these traits. The accessions can be classified into two groups according to the stereochemistry of the products accumulated: a group that displayed only 1R stereoisomers, and a group that displayed both 1S and 1R stereoisomers. (S)-cathinone reductase activities were detected in E. sinica stems capable of reducing (S)-cathinone to (1R,2S)-norephedrine and (1S,2S)-norpseudoephedrine in the presence of NADH. The proportion of the diastereoisomers formed varied according to the accession tested. A (1R,2S)-norephedrine N-methyltransferase capable of converting (1R,2S)-norephedrine to (1R,2S)-ephedrine in the presence of S-adenosylmethionine (SAM) was also detected in E. sinica stems. Our studies further support the notion that 1-phenylpropane-1,2-dione and (S)-cathinone are biosynthetic precursors of the ephedrine alkaloids in E. sinica stems and that the activity of (S)-cathinone reductases directs and determines the stereochemical branching of the pathway. Further methylations are likely due to N-methyltransferase activities.
- Krizevski, Raz,Bar, Einat,Shalit, Or,Sitrit, Yaron,Ben-Shabat, Shimon,Lewinsohn, Efraim
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experimental part
p. 895 - 903
(2010/08/19)
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- Synthesis of 2-Arylethylamines by the Curtius Rearrangement
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2-Arylethylamine derivatives were synthesized using the Curtius reaction and with three different methods of preparing the acyl azide functional group. Carbamates derived from isocyanate were convenient protecting groups for alkylation of amines. Starting from benzaldehyde, amphetamine was prepared in three steps through an oxazolidin-2-one intermediate in 62% overall yield. Copyright Taylor & Francis Group, LLC.
- Schulze, Matthias
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experimental part
p. 1461 - 1476
(2010/07/08)
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- The preparation of stable aziridinium ions and their ring-openings
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The reaction of enantiomerically pure 2-substituted 1-phenylethyl-aziridine with methyl trifluoromethanesulfonate generated a stable methylaziridinium ion, which was reacted with various external nucleophiles, including nitrile, to yield synthetically valuable and optically pure acyclic amine derivatives in a completely regio- and stereoselective manner. The Royal Society of Chemistry.
- Kim, Yongeun,Ha, Hyun-Joon,Yun, Sae Young,Lee, Won Koo
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supporting information; experimental part
p. 4363 - 4365
(2009/03/12)
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- Diastereoselective reduction of α-aminoketones: Synthesis of anti- and syn-β-aminoalcohols
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Reduction of N-t-BOC-protected-N-alkyl α-aminoketones with LiEt 3BH or Li(S-Bu)3BH furnishes protected syn-β-aminoalcohols with high selectivities. In contrast, removal of the BOC group followed by reduction of the aminoketone gives anti-β- aminoalcohols with variable selectivities. With aromatic ketones, selectivities are typically high while aliphatic ketones show mediocre to high selectivities depending on steric considerations.
- Fraser, David S.,Park, Sheldon B.,Chong, J. Michael
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- Determination of origin of ephedrine used as precursor for illicit methamphetamine by carbon and nitrogen stable isotope ratio analysis
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The sale of ephedrine, one of the precursors of methamphetamine, is strictly controlled and monitored in various countries to prevent the production of illicit methamphetamine. There are three kinds of production scheme for ephedrine manufacture, and it is very useful for precursor control to investigate the origin of ephedrine used for the synthesis of illicit methamphetamine. By means of stable isotope ratio mass spectrometry (IR-MS), we investigated the origin of ephedrine based on the δ13C and δ15N values. The various origins of ephedrine (biosynthetic, semisynthetic, or synthetic) could be discriminated clearly by using these values. The δ15N values of synthetic ephedrine were more negative than those of ephedrine from other sources. By the repeated distillation of methylamine in our laboratory, we confirmed that this could be due to isotope separation during distillation for the purification of methylamine used for ephedrine synthesis. The values for ephedrine used as the precursor were well-correlated with those for methamphetamine synthesized from it. This drug characterization analysis should be useful to illuminate the origin of the precursors used for clandestine methamphetamine and to trace the diversion of medicinal ephedrine for illicit manufacture of methamphetamine.
- Kurashima, Naoki,Makino, Yukiko,Sekita, Setsuko,Urano, Yasuteru,Nagano, Tetsuo
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p. 4233 - 4236
(2007/10/03)
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- Stereoisomers with high affinity for adrenergic receptors
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The present invention provides stereoscopically-pure diastereomers of Formula I: 1In a preferred embodiment, the stereoisomers of the present invention are of Formula II, depicted below: 2R2, R3 and le are independently H, OH, OCH3, CH2OH, NHCONH2, NH2, halogen or CF3, and R1 is pyridine, or an amine which may be substituted with hydrogen, lower alkyl, lower alkylenearyl, lower alkylenephenyl, lower alkylenehydroxyphenyl, lower alkyleneamine, lower alkyleneaminoaryl, lower alkylaminohydroxyphenyl, or a similar functional group. TV is hydrogen, hydroxyl or methyl; R6 is hydrogen, lower alkyl, lower alkylenaryl, lower alkylenephenyl, lower alkylenehydroxyphenyl, lower alkyleneamine, lower alkyleneaminoaryl, lower alkylaminohydroxyphenyl, and the like. For both Formula I and Formual II, the firs carbon on the side chain progressing from the ring is preferably in the R-configuration. The second carbon atom on the side chain of Formula II, which is attached to IV, may or may not be a chiral center. However, when the second carbon atom is a chiral center, it is preferably in the S-configuration. The present invention contemplates each stereoisomer of Formula I and II in substantially-pure form. The present invention also provides methods of relieving nasal, sinus and bronchial congestion and of treating attention deficit hyperactivity disorder and obesity. The present stereoisomers may also be used to induce pupil dilation. These methods include administering to a mammal a composition containing a therapeutically effective amount of a stereoscopically-pure stereoisomer of Formula I or II with a pharmaceutically acceptable excipient.
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- Process for the separation of a mixture of enantiomers
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A diastereomer complex obtained via a process for the separation of enantiomers is disclosed, wherein separation can be rapidly effected such that enantiomers are obtained with high e.e. values. The process pets the separation of mixtures of enantiomers in which more than one resolving agent is used, of which at least one resolving agent is optically active, and which yields a diastereomer complex containing at least two resolving agents in optically active form. The process provides for, inter alia, a diastereomer complex having at least three compounds of which at least two compounds are resolving agents in optically active form, and at least one compound is an onantiomer in optically active form. Also provided is a diastereomer complex having at least three compounds of which at lea one compound is a resolving agent in optically active form, and at least two compounds which are enantiomers in optically active form.
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- Process for producing optically active chrysanthemic acid
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The present invention provides an advantageous method for producing an optically active chrysanthemic acid. Disclosed is a method for producing an optically active chrysanthemic acid whose trans isomer ratio and optical purity are improved, which comprises reacting chrysanthemic acid having a trans isomer ratio of not less than 50% and an optical purity of not less than 10% e.e. with an optically active organic amine to optically resolve said chrysanthemic acid.
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- 2-AMINO-4-PHENYL-4-OXO-BUTYRIC ACID DERIVATIVES
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Use in the prevention and/or in the treatment of neurodegenerative diseases of 2-amino-4-phenyl-4-oxo-butyric acid derivatives which act as kynureninase enzyme inhibitors and/or kynurenine-3-hydroxylase enzyme inhibitors. Several of these derivatives are new and, as such, constitute a further object of this invention, together with the process for their preparation and the pharmaceutical compositions containing them.
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- Enantiomeric analysis of pharmaceutical compounds by Ion/molecule reactions
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Protonated complexes involving cyclodextrin hosts and guest compounds that are pharmacologically important are produced in the gas phase and reacted with a gaseous amine. The guest is exchanged to produce a new protonated complex with the amine. The reaction is enantioselective and is used to develop a method for determining enantiomeric excess using only mass spectrometry. The pharmaceutical compounds include DOPA, amphetamine, ephedrine, and penicillamine. The presence of more than one reacting species is observed with DOPA and penicillamine. Molecular dynamics calculations are used to understand the nature of the interactions and the possible source of the variations in the reactivities.
- Grigorean,Lebrilla
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p. 1684 - 1691
(2007/10/03)
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- Photocycloaddition of N-acyl enamines to aldehydes and its application to the synthesis of diastereomerically pure 1,2-amino alcohols
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The regio- and stereoselective synthesis of the protected cis-3- aminooxetanes cis-5 and cis-7 is reported. The oxetanes were obtained by the photocycloaddition of aliphatic (6c-e) and aromatic (4, 6a) aldehydes to the corresponding enamides (1a-d,h) or enecarbamates (1e-g). The enamine derivatives used in the Paterno-Buchi reaction were either commercially available or prepared from the corresponding acetaldehyde imines 2 by acylation. The oxetane formation proceeded with good-to-excellent simple diastereoselectivity for aromatic aldehydes (56-82% yield) and moderate selectivity for aliphatic aldehydes (46-55% yield). The cis-3-aminooxetanes are precursors for syn- and anti-1,2-amino alcohols. The relative configuration established in the photochemical step was retained upon nucleophilic ring opening between the oxygen atom and carbon atom C-4. By this means, syn-1,2-amino alcohols such as 8 and 10 were available in good yields. In contrast, the N-Boc-protected cis-3-aminooxetanes cis-5e and cis- 5f were transformed into anti-1,2-amino alcohols. Upon treatment with trifluoroacetic acid, they underwent an intramolecular nucleophilic substitution at the carbon atom C-2 of the oxetane and the oxazolidinones 11 and 12 were formed. Because the substitution occurs with inversion of configuration, anti-1,2-amino alcohols, e.g., ephedrine (15), are accessible.
- Bach,Schroder
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p. 1265 - 1273
(2007/10/03)
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- Method for producing optically active chrysanthemic acid
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The present invention provides an advantageous method for producing an optically active chrysanthemic acid. Disclosed is a method for producing an optically active chrysanthemic acid whose trans isomer ratio and optical purity are improved, which comprises reacting chrysanthemic acid having a trans isomer ratio of not less than 50% and an optical purity of not less than 10% e.e. with an optically active organic amine to optically resolve said chrysanthemic acid.
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- Fluoxetine process from benzoylpropionic acid
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A synthesis of fluoxetine is disclosed. The process begins with a lower alkyl ester of 3-benzoylpropionic acid, which is reduced in the presence of a chiral ligand to produce the corresponding γ-hydroxy ester, and the ester is cleaved. The free acid is then condensed with the alcohol to form a γ-lactone, which is treated with ammonia to provide the γ-hydroxy amide. The amide undergoes a Hoffman rearrangement to provide a 2-oxo-1,3 oxazine, which is reduced to 3-(methylamino)-1-phenyl-1-propanol. The alcohol is deprotonated and reacted with a 4-chloro- or 4-fluoro benzotrifluoride to provide fluoxetine free base.
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- Synthesis of syn- and anti-1,2-amino alcohols by regioselective ring opening reactions of cis-3-aminooxetanes
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N-t-Butyloxycarbonyl (Boc) substituted cis-2-phenyl-3-aminooxetanes 3 undergo a ring expansion to oxazolidinones 5 upon treatment with trifluoroacetic acid. The reaction occurs at the C(2) position under inversion of configuration. Alternatively, 3-aminooxetanes can be ring-opened at the less substituted C(4) position with retention of the relative configuration between C(2) and C(3) as exemplified by the synthesis of (+)-pseudoephedrine (2). The cis3-aminooxetanes serve as precursors for either syn- or anti-1,2-amino alcohols.
- Bach, Thorsten,Schroeder, Juergen
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p. 3707 - 3710
(2007/10/03)
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- Amino acid derivatives, the process for their preparation and their applications to therapy
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Amino acid derivatives of formula (Ia) and (Ib) and prodrugs thereof containing a group responsible for chelating the zinc atom of enkephalinase and angiotensin convertase enzymes are disclosed as inhibitors of these enzymes.
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- Stereoselective synthesis of (1R)- and (1R,2S)-1-aryl-2-alkylamino alcohols from (R)-cyanohydrins
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Hydrogenation of (R)-cyanohydrins (R)-1 with LiAlH4 occurs without racemization to give the (R)-2-amino alcohols (R)-3. (1R,2S)-2-Amino alcohols (1R,2S)-4 are obtained with high diastereoselectivity by addition of methyl Grignard to O-silyl protected cyanohydrins (R)-2 and subsequent hydrogenation with NaBH4. The N-alkylated 2-amino alcohols (R)-8 and (1R,2S)-9 can be prepared either by reductive alkylation of the corresponding 2-amino alcohols (R)-3 and (1R,2S)-4, respectively, or by a transimination reaction of the Grignard addition products with primary amines and subsequent hydrogenation with NaBH4. The lower diastereoselectivity of hydrogenation in case of the N-alkylmino compounds in comparison to the N-unsubstituted imines is explained by a weaker chelating effect.
- Effenberger, Franz,Gutterer, Beate,Jaeger, Juergen
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p. 459 - 467
(2007/10/03)
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- Chiral separation of drug enantiomers by capillary electrophoresis using succinyl-β-cyclodextrin
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A capillary electrophoretic method for the enantiomeric separation of 11 drugs was developed using an uncoated fused-silica capillary and succinyl β-cyclodextrin as a chiral additive. The effect of the pH of the background electrolyte on selectivity and resolution was studied in the range pH 3.3-9.3. Best results were obtained in a neutral medium. Generally, the presence of a hydroxy group at the chiral C-atom of the analyte seems to be essential because similar compounds without a hydroxy group at the chiral centre did not show chiral resolution. In addition to the enantioselective inclusion into the chiral cavity, hydrogen bondings and formation of ion pairs between the negatively charged selector and cationic analytes can be assumed as mechanisms.
- Schmid,Wirnsberger,Guebitz
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p. 852 - 854
(2007/10/03)
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- Saponification agents. 2. Synthesis of arylisocyanates with ethyl lactate and their use in racemic bases saponification
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Reaction of the arylisocyanates 2a-c with ethyl (S)-(-)-lactate, followed by careful saponification, afforded the corresponding chiral acids (S)-(-)- 4a-c. The latter were successfully used for the resolution of various racemic bases belonging to both the ephedrine and α-aryl ethylamine series.
- Brown,Moudachirou
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p. 10309 - 10320
(2007/10/02)
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- Application of the Mitsunobu reaction to ephedrines and some related amino alcohols. Aspects of intramolecular participation of the amino group
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Inversion of configuration at the benzylic hydroxyl group of (1S,2S)-pseudoephedrine (2) to afford (1R,2S)-ephedrine is known to be a difficult process.The Mitsunobu reactions of 1 and 2 might offer a route to achieve such inversions.In fact Mitsunobu reactions on 1 and 2 are known to proceed via aziridines formed on intramolecular SN2 substitution by the amine functionality.The Mitsunobu reactions of N-methylated and N-benzylated ephedrines have been found to proceed via the corresponding aziridinium ions.These aziridinium ions can be opened (SN2 substitution) by nucleophiles like phthalimide and thiols.Intramolecular participation in 2 can be avoided by use of the tert-butyloxycarbonyl-(BOC) or benzyloxycarbonyl- (CBZ) protected derivatives.Mitsunobu reactions on these derivatives lead to inversion of configuration at the benzylic hydroxyl center.In contrast the BOC and CBZ derivatives of 1 are deprotected under Mitsunobu conditions.The Mitsunobu reactions of threo (1S,2S)-2-amino-1,3-propanediol have also been examined.An attempt to achieve protection by reaction with dimethylformamide dimethyl acetal led to the more substituted 2-oxazoline as established by X-ray crystallography.The desired inversion of configuration of the benzylic hydroxylic group was eventually achieved by protection of the amino substituent as the phthalimide and protection of the primary hydroxyl group as the tosylate.
- Poelert, Martin A.,Hulshof, L. A.,Kellogg, Richard M.
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p. 355 - 364
(2007/10/02)
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- Method for producing optically active amines
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A method for producing an optically active amine which is an important compound as a resolving agent for medicines, agricultural chemicals, intermediates thereof, etc is disclosed.
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- Practical palladium-mediated deprotective method of allyloxycarbonyl in aqueous media
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The Allyloxycarbonyl (Alloc) moiety can be removed smoothly and selectively in good yield (73-100%) from allylic esters, carbamates and carbonates by aqueous Pd (O) catalysed allyl transfer to diethylamine in aqueous media employing a water soluble phosphine. The allyl scavenger as well as by product allyl diethylamine are volatile and easily removed in vacuo. In a two phase system an increased selectivity is seen. The method has been successfully used for deprotection of a wide range of secondary amines or base sensitive derivatives and the catalyst is efficiently recycled.
- Genet, Jean Pierre,Blart, Errol,Savignac, Monique,Lemeune, Stephane,Lemaire-Audoire, Sandrine,Paris, Jean-Marc,Bernard, Jean-Marie
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p. 497 - 503
(2007/10/02)
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- PREPARATION OF BOTH ENANTIOMERS OF (1R*, 2S*)-1-CYCLOHEXYL-1,2-PROPANEDIOL FROM THE COMMERCIAL NEUBERG'S KETOL
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Both the optically pure enantiomers of (1R*,2S*)-1-cyclohexyl-1,2-propanediol (II) were prepared from commercial (R)-(-)-1-phenyl-1-hydroxy-2-propanone (I; Neuberg's ketol). (1R,2S)-(+)-1-Cyclohexyl-1,2-propanediol(+)-II) was obtained in 19percent total yield, its (1S,2R)-enantiomer ((-)II) in 8percent yield.Both diols, as well as their precursors, enantiomeric (1R*,2S*)-1-phenyl-1,2-propanediols (IIIa), are suitable chiral synthons.
- Cervinka, Otakar,Struzka, Vladimir
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p. 2685 - 2691
(2007/10/02)
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- Applications of Optically Active Aryl Cyanohydrins in the Synthesis of α-Hydroxy Aldehydes, α-Hydroxy Ketones and β-Hydroxy Amines
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Cyanohydrins, prepared in high optical purity from aryl aldehydes, have been converted into α-hydroxy aldehydes, α-hydroxy ketones and β-hydroxy amines without any racemization and frequently with good stereoselectivity for the erythro-diastereoisomer (>90percent) at the newly introduced stereogenic centre.
- Jackson, W. Roy,Jacobs, Howard A.,Jayatilake, Gamini S.,Matthews, Barry R.,Watson, Keith G.
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p. 2045 - 2062
(2007/10/02)
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- Stereoselectrive Syntheses of Ephedrine and Related 2-Aminoalcohols of High Optical Purity from Protected Cyanohydrins
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Ephedrine and related optically active β-aminoalcohols can be prepared by zinc borohydride reduction of aryl O-protected magnesium imines and aryl α-hydroxyimimes which in turn are readily available from optically active cyanohydrins.
- Jackson, W. Roy,Jacobs, Howard A.,Matthews, Barry R.,Jayatilake, Gamini S.,Watson, Keith G.
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p. 1447 - 1450
(2007/10/02)
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- Threo-adrenalinecarboxylic acid, and the production and uses thereof
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DL- or L-Threo-3-(3,4-dihydroxyphenyl)-N-methyl-serine which may also be termed as DL- or L-threo-adrenalinecarboxylic acid are now provided, which are new compounds useful for therapeutic treatment of Parkinson's disease and mental depression disease. DL-Adrenalinecarboxylic acid may be produced by a new process comprising reacting glycine with O-protected 3,4-dihydroxybenzaldehyde, hydrolyzing the resultant reaction product under acidic conditions to form O-protected DL-3-(3,4-dihydroxyphenyl)serine, isolating the O-protected DL-3-(3,4-dihydroxyphenyl)serine into the threo isomer and the erythro isomer by recrystallization from a suitable organic solvent, introducing an unsubstituted or substituted benzyl group into the 2-amino group of the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine, then N-methylating the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl )-N-benzylserine, and removing the O-protecting groups as well as the unsubstituted or substituted benzyl group at the 2-methylamino group of the N-methylation product. L-Adrenalinecarboxylic acid may be produced by a new process comprising introducing a p-methoxybenzyloxycarbonyl group into the 2-amino group of the O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine obtained as an intermediate product, optically resolving the resultant O-protected DL-threo-3-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine by reacting the latter with an optically active amine and recrystallizing the resultant amine salt products from a suitable organic solvent, removing the p-methoxy-benzyloxycarbonyl group from the resultant O-protected L-threo-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine, reacting the resultant O-protected L-threo-(3,4-dihydroxyphenyl)serine with dimethyl sulfate in dry acetone to form an O-protected L- or D-threo-(3,4-dihydroxyphenyl)-N-methylserine methyl ester, saponifying this methyl ester and then removing the O-protecting groups from the saponification product.
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- Pharmaceutical formula
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The present invention concerns a pharmacological vehicle or carrier system, which makes possible administration of the active ingredient with a high absorption thereof in the blood circulation of the patient treated therewith, in particular also in the case of oral administration. The pharmacological vehicle system according to the invention comprises ultrafine particles of a reaction product of a reactive derivative of an at least dibasic inorganic acid or an alkane-carboxylic acid having 2 or 3 carboxyl groups and optionally one or two hydroxy groups, wherein one bond of the dibasic inorganic acid or one carboxy group of the alkane-carboxylic acid is bonded to a pharmacological active ingredient containing a hydroxy group, SH group and/or a primary or secondary amino group having a ractive hydrogen atom on this group, and the other bond is bonded to the free hydroxy group of a glycerolipid having at least one free hydroxy group on the glycerol. The invention further concerns these reaction products and a process for the preparation of ultrafine particles of these reaction products.
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- Synthesis and Stereoselective Reactions of 2-(Pyrrol-1-yl)alkanals and 2-(pyrrol-1-yl)alkan-1-ones
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2-(2,5-Dimethylpyrrol-1-yl)alkanals, 2-(pyrrol-1-yl)alkanals, and 2-(2,5-dimethylpyrrol-1-yl)alkan-1-ones were prepared.The reactions of these compounds with Grignard and hydride reagents proceeded stereoselectively to give the corresponding 2-(pyrrol-1-yl)alcohols, which were converted into 2-aminoalcohols, such as norephedrine and ephedrine, by cleavage of the pyrrole ring.
- Kashima, Choji,Maruyama, Tatsuya,Fujioka, Yoko,Harada, Kazuo
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p. 1041 - 1046
(2007/10/02)
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- Chiral Discrimination in the Structures and Energetics of Association of Stereoisomeric Salts of Mandelic Acid with α-Phenethylamine, Ephedrine, and Pseudoephedrine
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A careafully coordinated study of the relations between structure and energetics of association in the crystalline state and solution is reported here.Hydrogen-bonded ion pairs formed from reaction between the enantiomers of mandelic acid, α-phenethylamine, ephedrine, and pseudoephedrine have been studied in dimethyl sulfoxide, dioxane, and water and as solid salts.Single-crystal X-ray analysis, performed on four unique diastereomeric pairs of (+/-)-ephedrinium and (+/-)-pseudoephedrinium (+/-)-mandelates yielded details of the solid-state hydrogen-bonding schemes for all eight diastereomeric salts. 1H NMR spectra (at 300 and 600 MHz) over a wide concentration range were determined and indicated a simple two-state equilibrium between ion pairs and free ions in dimethyl sulfoxide.The dissociation equilibria in dimethyl sulfoxide were examined more quantitatively by conductance and the results treated by the Fuoss-Justice, Fuoss-1977, and Onsager methods to yield calculated dissociation constants, equivalent conductances, and mean activity coefficients over a wide concentration range.Thermochemical properties determined by various techniques were (1) the heat of fusion by differential scanning calorimetry, (2) heats of solution of the crystalline salts to high dilution by isoperibolic batch calorimetry, and (3) heats of protonation and heats of dissociation from thermometric titration of solutions of mandelic acid with the bases.Extensive use was made of cross-chiral checks (e.g., R,R' vs S,S') to prove that observed chiral discrimination factors were real and accurate.Significant chiral discrimination factors were found for all properties of diastereomeric combinations.In several cases the largest differences in thermochemical properties and 1H NMR spectra of diastereomeric pairs could be related reasonably to differences in hydrogen-bonding schemes in their crystals.
- Zingg, S. P.,Arnett, Edward M.,McPhail, Andrew T.,Bothner-By, Aksel A.,Gilkerson, W. R.
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p. 1565 - 1580
(2007/10/02)
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- Erythro-Directive Reduction of α-Substituted Alkanones by Means of Hydrosilanes in Acidic Media
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Hydrosilane reduced α-oxy and α-amino ketones and β-keto acid derivatives in trifluoroacetic acid to afford the corresponding erythro alcohols with high diastereoselectivity.The reaction proceeded without racemization at the carbon α to the carbonyl group.The erythro-directive reduction was explained in terms of the proton-bridged Cram cyclic model and successfully applied to the synthesis of physiologically important amino alcohols such as l-ephedrine, l-methoxamine, and erythro-2-methyl-3-piperidino-1-phenylpropanol.
- Fujita, Makoto,Hiyama, Tamejiro
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p. 5415 - 5421
(2007/10/02)
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- Resolution of Racemic Amines with 2-Methyl-2-phenylbutanedioic Acid
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Five racemic amines were resolved in high chemical and optical yields using (S)-(+)-2-methyl-2-phenylbutanedioic acid as resolving reagent.The reagent can be recovered quantitatively and without any change in its optical purity. (R)-(-)-2-Methyl-2-phenylbutanedioic acid was also obtained.
- Gharpure, Milind M.,Rao, A. S.
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p. 410 - 411
(2007/10/02)
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- Regeneration of 6-fluoro-4-chromanone from 6-fluoro-4-ureidochroman-4-carboxylic acid
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6-Fluoro-4-chromanone can be regenerated from (R)-6-fluoro-4-ureidochroman-4-carboxylic acid, or from mixtures of (R)-6-fluoro-4-ureidochroman-4-carboxylic acid and its racemic modification, by oxidation with a permanganate, especially potassium permanganate. 6-Fluoro-4-chromanone is a chemical intermediate useful for preparing sorbinil, an aldose reductase inhibitor which can be used in clinical medicine for the control of the chronic complications of diabetes. (R)-6-Fluoro-4-ureidochroman-4-carboxylic acid and its racemic modification are by-products from the production of sorbinil from 6-fluoro-4-chromanone.
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- Anodic Oxidation of Amines. VII. Oxidation of β-Alkanolamines in Aqueous Buffer of pH 10
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The anodic oxidation of several different types of β-alkanolamines, R1R2C(OH)CR3R4NR5R6, was studied by cyclic voltammetry and controlled potential electrolysis in an aqueous carbonat buffer of pH 10 at a glassy carbon electrode.Upon oxidation, both the (α)C-(β)C and the C-N bonds are cleaved.Substituents R1-R4 affect the first oxidation potential and product distribution.The relative rates of the bond cleavages were estimated from the oxidation products.It was found that most of the amine cleaves through the (α)C-(β)C bond when at least one of the R groups is phenyl, nearly half cleaves through this bond when R is alkyl, and only about a tenth does so when R1-R4 are all hydrogen.The stability of the transient intermediates at the e-c step of the e-c-e process seems to affect the oxidation potentials and to govern the relative rates of the (α)C-(β)C bond cleavage.A scheme for the reaction processes is proposed.Keywords---β-alkanolamines; anodic oxidation; (α)C-(βC) bond fission; C-N bond fission; carbonate buffer; aldehyde; acetone; glycolaldehyde
- Masui, Masaichiro,Kamada, Yoshiyuki,Sasaki, Etuko,Ozaki, Shigeko
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p. 1234 - 1243
(2007/10/02)
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- SYNTHESES ASYMETRIQUES A L'AIDE D'OXAZOLIDINES CHIRALES DERIVEES DE L'EPHEDRINE. PREPARATION DE FORMYL CYCLOPROPANES CHIRAUX.
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Chiral oxazolidines 2 are very simple and highly efficient inducing groups for asymmetric synthesis during cycloaddition reactions.Chiral formyl cyclopropanes are easily obtained in high enantiomeric excess (>= 90 percent).
- Abdallah, Hassan,Gree, Rene,Carrie, Robert
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p. 503 - 506
(2007/10/02)
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- α-Amino Acids as Chiral Educts for Asymmetric Products. Amino Acylation with N-Acylamino Acids
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α-N-Acylamino acids have been developed as useful reagents for the preparation of optically pure α-aminoalkylaryl ketones.Protection of the amino group as either the ethoxycarbonyl or benzenesulfonyl derivative allows alanine to serve as an effective educt for the chirally specific synthesis of a variety of structures containing the phenylethylamine backbone.Benzene undergoes Friedel-Crafts acylation with the N-acylalanine acid chloride.Catalyst complexation with oxagenated aromatics, however, prohibits acylation of aryl ethers.An arylmetallo reaction scheme overcomes this problem and also affords regiospecificity not attainable in conventional acylations.As examples, optically pure ephedrines and amphetamines were directly synthesized without recourse to resolution since the chirality of the amino acid educt was entirely conserved throughout the process.
- Buckley, Thomas F.,Rapoport, Henry
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p. 6157 - 6163
(2007/10/02)
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- Process for converting esters to amine salts
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A new method for converting certain diesters to physiologically acceptable amines which comprises reacting the diester with the desired amine in a solvent consisting essentially of water.
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