- SYNTHESIS OF α-SUBSTITUTED α-AMINO ACIDS BY THE ALKYLATION OF 5-OXAZOLINONE DERIVATIVES
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Methods have been developed for the alkylation of 5-oxazolinone derivatives in DMF in the presence of K2CO3, KOH, or diisopropylethylamine and a phase transfer catalyst as well as for the preparation of α-methylphenylalanine, α-methylalanine, α-methylalanine, and the methyl ester of N-benzoyl-α-methylalanine.Increasing the initial concentration of the starting 5-oxazolinone in the reaction mixture leads to a sharp drop in the yield of reaction products due to side condensation reactions.The reaction of 2-phenyl-4-benzyl-5-oxazolinonewith ethyl iodide gave a dimer, mamely, 3-(benzoylamino)-3,5-dibenzylpyrrolidine-2,4-dione.
- Slavinskaya, V. A.,Sile, D. E.,Katkevich, M. Yu.,Korchagova, E. Kh.,Lukevits, E.
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- Application of metal reagent to the asymmetric synthesis of α-αamino acids
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Using "mix-ligands" type chiral synthons containing metal ions, a,a-amino acids were obtained in "one-pot" reactions in moderate to high yields and ee% values.
- Hu, Ai-Guo,Zhang, Ling-Yun,Wang, Shan-Wei,Wang, Ji-Tao
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- Catalytic, asymmetric synthesis of α,α-disubstituted amino acids
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Copper(salen) complex 1 has been found to catalyse the asymmetric alkylation of enolates derived from a variety of amino acids. There is a clear relationship between the size of the side chain in the substrate and the enantioselectivity of the process, so that the enantioselectivity decreases in the order alanine>aminobutyric acid>allylglycine>leucine>phenylalanine>valine. A transition state model which accounts for the influence of the size of the side chain on the enantioselectivity of the reactions is presented.
- Belokon', Yuri N.,Bhave, Devayani,D'Addario, Daniela,Groaz, Elizabetta,Maleev, Viktor,North, Michael,Pertrosyan, Armine
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- Enantiocatalytic activity of substituted 5-benzyl-2-(pyridine-2-yl) imidazolidine-4-one ligands
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Currently, asymmetric synthesis represents one of the main streams of organic synthesis. Although an extensive research has been carried out in this area, the synthesis of chiral compounds with the required enantiomeric purity is still a challenging issue. Herein, we focus on the preparation of new enantioselective catalysts based on pyridine-imidazolidinones. The substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-ones 5-8 were prepared by condensation of chiral amino acid amides (α-methylDOPA and α- methylphenylalanine) with 2-acetylpyridine and pyridine-2-carbaldehyde. The individual isomers of the described ligands 5-8 were separated chromatographically. The copper(II) complexes of these chiral ligands were studied as enantioselective catalysts for the asymmetric Henry reaction of substituted aldehydes with nitromethane or nitroethane. The ligands containing a methyl group at the 2-position of the imidazolidinone ring 6a and 8a exhibit a high degree of enantioselectivity (up to 91% ee). The nitroaldols derived from nitroethane (2-nitropropan-1-ols) were obtained with a comparable enantiomeric purity to derivatives of 2-nitroethanol. This group of ligands represents a new and promising class of enantioselective catalysts, which deserve further attention.
- Drabina, Pavel,Karel, Sergej,Panov, Illia,Sedlak, Milos
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p. 334 - 339
(2013/04/23)
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- Lyaseenzymes, Nucleic Acids Encoding Them and Methods For Making and Using Them
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This invention provides polypeptides having lyase activity, polynucleotides encoding these polypeptides, and meth-°ds of making and using these polynucleotides and polypeptides. In one aspect, the invention is directed to polypeptides having ammonia lyase activity, e.g., phenylalanine ammonia lyase, tyrosine ammonia lyase and/or histidine ammonia lyase activity, including thermostable and thermotolerant activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The polypeptides of the invention can be used in a variety of pharmaceutical, agricultural and industrial contexts. X═NO2, Cl, Br, NH2, OH, H, alkyl at one or several o, m, and p positions R═H or alkyl.
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- Lyase Enzymes, Nucleic Acids Encoding Them and Methods for Making and Using Them
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This invention provides polypeptides having lyase activity, polynucleotides encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides. In one aspect, the invention is directed to polypeptides having ammonia lyase activity, e.g., phenylalanine ammonia lyase, tyrosine ammonia lyase and/or histidine ammonia lyase activity, including thermostable and thermotolerant activity, and polynucleotides encoding these enzymes, and making and using these polynucleotides and polypeptides. The polypeptides of the invention can be used in a variety of pharmaceutical, agricultural and industrial contexts.
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- Versatile synthesis of free and N-benzyloxycarbonyl-protected 2,2-disubstituted taurines
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An effective and versatile method was developed to synthesize N-benzyloxycarbonyl-protected and free 2,2-disubstituted taurines. Several novel 2,2-disubstituted taurines, including aliphatic/aromatic and cyclic/acyclic derivatives, were obtained, which demonstrates the generality of this method. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Wang, Boyuan,Zhang, Wei,Zhang, Leilei,Du, Da-Ming,Liu, Gang,Xu, Jiaxi
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p. 350 - 355
(2008/09/18)
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- Asymmetric PTC C-Alkylation Catalyzed by Chiral Derivatives of Tartaric Acid and Aminophenols. Synthesis of (R)- and (S)-α-Methyl Amino Acids
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A new type of efficient chiral catalyst has been elaborated for asymmetric C-alkylation of CH acids under PTC conditions. Sodium alkoxides formed from chiral derivatives of tartaric acid and aminophenols (TADDOL's 2a-e and NOBIN's 3a-h) can be used as chiral catalysts in the enantioselective alkylation, as exemplified by the reaction of Schiffs bases la-e derived from alanine esters and benzaldehydes with active alkyl halides. Acid-catalyzed hydrolysis of the products formed in the reaction afforded (R)-α-methylphenylalanine, (R)-α-naphthylmethylalanine, and (R)-α-allylalanine in 61-93% yields and with ee 69-93%. The procedure could be successfully scaled up to 6 g of substrate 1b. When (S,S)-TADDOL or (R)-NOBIN are used, the (S)-amino acids are formed. A mechanism rationalizing the observed features of the reaction has been suggested.
- Belokon, Yuri N.,Kochetkov, Konstantin A.,Churkina, Tatiana D.,Ikonnikov, Nikolai S.,Chesnokov, Alexey A.,Larionov, Oleg V.,Singh, Ishwar,Parmar, Virinder S.,Vyskocil, Stepan,Kagan, Henri B.
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p. 7041 - 7048
(2007/10/03)
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- Asymmetric alkylation catalyzed by chiral alkali metal alkoxides of TADDOL. Synthesis of α-methyl amino acids
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It is shown that sodium alkoxides formed from (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-bis(diphenylmethanol) ((R,R)-TADDOL) and some of its derivatives can be used as chiral catalysts for enantioselective alkylation of Schiff's bases derived from alanine with reactive alkyl halides. Acid hydrolysis of the reaction products affords (R)-α-methytphenyl-alanine, (R)-α-allylalanine, and (R)-α-methylnaphthylalanine in 61-93% yields and with ee 69-94%. When (S,S)-TADDOL is used, the (3)-amino acid is formed. A mechanism explaining the observed features of the reaction is proposed.
- Belokon',Kochetkov,Churkina,Ikonnikov,Chesnokov,Larionov,Kagan
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p. 917 - 923
(2007/10/03)
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- γ-Substituted pyrrole-based silyl dienol ethers as α-amino acid enolate equivalents: a versatile entry to racemic α-substituted α-amino acids
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γ-Substituted siloxypyrrole derivatives 5-7 have been synthesized by direct alkylation of N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole 1.These underwent subsequent alkylation with alkyl halides or aldehydes to produce γ,γ-disubstituted α,β-unsaturated lactam intermediates in good yields.Oxidative cleavage of the C(3)-C(4) bond within the lactam moiety gave rise to a number of α-substituted α-amino acids.These include racemic α-methylphenylalanine 14, α-benzylphenylalanine 15, α-benzylserine 18 and α-methylthreonine 21.
- Zanardi, Franca,Battistini, Lucia,Rassu, Gloria,Cornia, Mara,Casiraghi, Giovanni
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p. 2471 - 2476
(2007/10/02)
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- Furan-, pyrrole-, and thiophene-based siloxydienes for syntheses of densely functionalized homochiral compounds
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This review describes the methods of preparation and use of 2-(trimethylsiloxy)furan, N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole, and certain substituted analogues and congeners, including novel 2-(tert-butyldimethylsiloxy)thiophene, to synthesize complex carbohydrates, azasugars, polyhydroxylated alkaloids, C-glycosylated α-amino acids, amino acids bearing quaternary chiral carbon atoms, and thiosugars. Especially emphasized is the preparation of enantiomerically pure compounds of biological interest. Some mechanistic insights are presented.
- Casiraghi,Rassu
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p. 607 - 626
(2007/10/02)
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- Chemo-Enzymic Synthesis of Optically Active α,α-Disubstituted α-Amino Acids
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A series of α,α-disubstituted α-amino esters was chemically synthesized and then resolved through enantioselective hydrolysis catalysed by a new enzyme isolated from crude Humicola langinosa lipase.This enzyme only accepts free amino esters as substrates with neither lipase activity toward olive oil nor esterase activity toward o-nitrophenyl butyrate.It is unique in that it successfully catalyses the resolution of amino esters with two large α-alkyl groups including aliphatic, aromatic and cyclic amino esters.Examples of resolutions where the alkyl groups differ in size by as little as a single carbon atom have been demonstrated.For determination of absolute configuration, some of the optically active α,α-disubstituted amino acids were also prepared through Schoellkopf's asymmetric synthesis and the structures were verified by X-ray crystallography.A model depicting the substrate binding site of the enzyme is proposed.
- Liu, Weiguo,Ray, Paul,Benezra, Steven A.
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p. 553 - 560
(2007/10/02)
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- TRANSITION METAL COMPLEXES - A NEW CLASS OF CATALYSTS OF INTERFACIAL ALKYLATION FOR THE ASYMMETRICAL SYNTHESIS OF α-AMINO ACIDS
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A new class of catalysts of interfacial asymmetrical alkylation is suggested for the synthesis of α-amino acids - positively charged complexes of the transition metals Cu(II), Ni(II), and Pd(II).These complexes consist of several fragments, by variation of which the structure of the catalysts can readily be modified.The complexes are chiral on account of (S)proline derivatives contained in them as one of the fragments.The catalyst complexes (C) were used in alkylation of amino acid fragments of Ni(II) complexes of the Schiff base of glycine with N-(2-pyridinecarbonyl)-o-aminobenzophenone (Ni-PBP-Gly) and the Schiff base of alanine with N-(2-pyridinecarbonyl)-o-aminobenzaldehyde (Ni-PBA-Ala) under interfacial conditions.After decomposition of alkylated complexes, phenylalanine and α-methyl-phenylalanine were isolated with yields of 33-87percent and optical purity (o. p.) from 3 to 21percent, depending on the C used.
- Belokon', Yu. N.,Maleev, V. I.,Videnskaya, S. O.,Saporovskaya, M. B.,Tsyryapkin, V. A.,Belikov, V. M.
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p. 110 - 118
(2007/10/02)
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- SOLID-LIQUID PHASE TRANSFER CATALYTIC SYNTHESIS OF α-AMINO ACID VIA ALKYLATION AND NUCLEOPHILIC ADDITION OF BENZALDEHYDE IMINES
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A short, mild and efficient synthetic route of α-amino acid via alkylation, Michael addition and carbonyl addition as well as cycloaddition of aldimines derived from glycine and alanine esters with benzaldehyde under solid-liquid phase transfer catalytic condition has been studied.The key to solid-liquid phase transfer catalyzed reactions is the selection of a base for the various reactants.The yield is dependent on the base used.The results obtained using KOH, K2CO3 and Na2CO3 are discussed.The kinetics of solid-liquid PTC benzylation has been investigated and we propose a possible mechanism of solid-liquid PTC as an interface auto-catalytic procedure.The details of some syntheses of α-amino acids are presented.
- Yaozhong, Jiang,Changyou, Zhou,Shengde, Wu,Daimo, Chen,Youan, Ma,Guilan, Liu
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p. 5343 - 5354
(2007/10/02)
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- Acidities of Glycine Schiff Bases and Alkylation of Their Conjugate Bases
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Equilibrium acidities in Me2SO are reported for six ketimines of the type Ph2C=NCH(R)CO2Et and five aldimines, ArCH=NCH(R)CO2Et.Changing R in the ketimine from H to Ph increased the pKa by 2.2 units.This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa of 3.8 and 4.2 units observed for the replacement of hydrogen by Me and PhCH2, respectively.Phase-transfer alkylation of the Ph2C=NCH2CO2Et ketimine gave over 90 percent of monoalkylate whereas, under similar conditions, the aldimine 4-ClC6H4CH=NCH2CO2Et gave a mixture of mono- and dialkylate.The difference is that the pKa of the monoalkylated aldimine is essentially the same as that of the parent, which leads to rapid equilibration with the parent anion and consequent dialkylation.The rates of alkylation in Me2SO of these parent and monoalkylated anions did not differ greatly, showing that the relative pKHAs of the parent acid and its monoalkyl derivative, rather tham the relative rates of the mono- and dialkylation reactions, is the principal factor that determines the extent of the competition between monoalkylation and dialkylation.
- O'Donnell, Martin J.,Bennett, William D.,Bruder, Willian A.,Jacobsen, William N.,Knuth, Keith,et al.
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p. 8520 - 8525
(2007/10/02)
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