- Synthesis of Optically Pure (S, E)-2-Amino-5-arylpent-4-enoic Acids by Heck Reactions of Nickel Complexes
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Starting from commercially available building blocks a variety of enantiomerically pure (S)-2-amino-4-enoic acids has been synthesized by the Heck reaction using Ni-(S)-BPB {Nickel- N -[(S)-benzylprolyl]aminobenzophenone} as a chiral auxiliary. The reactions proceeded in very good yields and with high E -selectivity.
- Parpart, Silvio,Mardiyan, Zorayr Z.,Ehlers, Peter,Petrosyan, Andranik,Mkrtchyan, Anna F.,Saghyan, Ashot S.,Langer, Peter
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- Convenient, large-scale asymmetric synthesis of enantiomerically pure trans-cinnamylglycine and -α-alanine
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Asymmetric syntheses of (S)-trans-cinnamylglycine and (S)-α-trans- cinnamyl-α-alanine via reactions of cinnamyl halides (Cl, Br) with Ni(II)- complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N- benzylprolyl)amino]benzophenone were
- Qiu, Wei,Soloshonok, Vadim A.,Cai, Chaozhong,Tang, Xuejun,Hruby, Victor J.
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- Tailored Mutants of Phenylalanine Ammonia-Lyase from Petroselinum crispum for the Synthesis of Bulky l- and d-Arylalanines
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Tailored mutants of phenylalanine ammonia-lyase from Petroselinum crispum (PcPAL) were created and tested in ammonia elimination from various sterically demanding, non-natural analogues of phenylalanine and in ammonia addition reactions into the corresponding (E)-arylacrylates. The wild-type PcPAL was inert or exhibited quite poor conversions in both reactions with all members of the substrate panel. Appropriate single mutations of residue F137 and the highly conserved residue I460 resulted in PcPAL variants that were active in ammonia elimination but still had a poor activity in ammonia addition onto bulky substrates. However, combined mutations that involve I460 besides the well-studied F137 led to mutants that exhibited activity in ammonia addition as well. The synergistic multiple mutations resulted in substantial substrate scope extension of PcPAL and opened up new biocatalytic routes for the synthesis of both enantiomers of valuable phenylalanine analogues, such as (4-methoxyphenyl)-, (napthalen-2-yl)-, ([1,1′-biphenyl]-4-yl)-, (4′-fluoro-[1,1′-biphenyl]-4-yl)-, and (5-phenylthiophene-2-yl)alanines.
- Filip, Alina,Nagy, Emma Z. A.,Tork, Souad D.,Bánóczi, Gergely,To?a, Monica I.,Irimie, Florin D.,Poppe, László,Paizs, Csaba,Bencze, László C.
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p. 2627 - 2633
(2018/05/03)
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- Expanding the substrate scope of phenylalanine ammonia-lyase from: Petroselinum crispum towards styrylalanines
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This study focuses on the expansion of the substrate scope of phenylalanine ammonia-lyase from Petroselinum crispum (PcPAL) towards the l-enantiomers of racemic styrylalanines rac-1a-d-which are less studied and synthetically challenging unnatural amino acids-by reshaping the aromatic binding pocket of the active site of PcPAL by point mutations. Ammonia elimination from l-styrylalanine (l-1a) catalyzed by non-mutated PcPAL (wt-PcPAL) took place with a 777-fold lower kcat/KM value than the deamination of the natural substrate, l-Phe. Computer modeling of the reactions catalyzed by wt-PcPAL indicated an unproductive and two major catalytically active conformations and detrimental interactions between the aromatic moiety of l-styrylalanine, l-1a, and the phenyl ring of the residue F137 in the aromatic binding region of the active site. Replacing the residue F137 by smaller hydrophobic residues resulted in a small mutant library (F137X-PcPAL, X being V, A, and G), from which F137V-PcPAL could transform l-styrylalanine with comparable activity to that of the wt-PcPAL with l-Phe. Furthermore, F137V-PcPAL showed superior catalytic efficiency in the ammonia elimination reaction of several racemic styrylalanine derivatives (rac-1a-d) providing access to d-1a-d by kinetic resolution, even though the d-enantiomers proved to be reversible inhibitors. The enhanced catalytic efficiency of F137V-PcPAL towards racemic styrylalanines rac-1a-d could be rationalized by molecular modeling, indicating the more relaxed enzyme-substrate complexes and the promotion of conformations with higher catalytic activities as the main reasons. Unfortunately, ammonia addition onto the corresponding styrylacrylates 2a-d failed with both wt-PcPAL and F137V-PcPAL. The low equilibrium constant of the ammonia addition, the poor ligand binding affinities of 2a-d, and the non-productive binding states of the unsaturated ligands 2a-d within the active sites of either wt-PcPAL or F137V-PcPAL-as indicated by molecular modeling-might be responsible for the inactivity of the PcPAL variants in the reverse reaction. Modeling predicted that the F137V mutation is beneficial for the KRs of 4-fluoro-, 4-cyano- and 4-bromostyrylalanines, but non-effective for the KR process of 4-trifluoromethylstyrylalanine.
- Bencze, László Csaba,Filip, Alina,Bánóczi, Gergely,To?a, Monica Ioana,Irimie, Florin Dan,Gellért, ákos,Poppe, László,Paizs, Csaba
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p. 3717 - 3727
(2017/07/07)
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- Microwave-assisted synthesis of unnatural amino acids
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Microwave irradiation has been proven to be a useful tool in the rapid assembly of racemic unnatural amino acids in only two steps. Additional benefits of this methodology are the commercial availability of the inexpensive starting materials and the high yields and high purities of the final amino acid products.
- Young, Douglas D.,Torres-Kolbus, Jessica,Deiters, Alexander
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experimental part
p. 5478 - 5480
(2009/05/30)
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- Direct synthesis of unprotected α-amino acids via allylation of hydroxyglycine
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Hydroxyglycine, the ammonia adduct of glyoxylic acid, was found to react with various allylboronates in the presence of triethylamine in methanol to give unprotected α-amino acids directly with high stereoselectivity. For instance, the reactions with (E)- and (Z)-crotylboronates afforded the corresponding anti- and syn-crotylated products (isoleucine and alloisoleucine after hydrogenation) with high diastereoselectivity, respectively. Interestingly, it was found that isomerization of the products (γ-adducts to α-adducts) occurred under the reaction conditions in some cases. Control experiments have suggested that the isomerization took place via 2-aza (or azonia) Cope rearrangement of imines derived from γ-adducts and glyoxylic acid.
- Sugiura, Masaharu,Mori, Chieko,Hirano, Keiichi,Kobayashi, Shu
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p. 937 - 942
(2007/10/03)
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- Single chain peptide compounds having hemoregulatory activity
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There is disclosed single chain peptide compounds, substituted at a Cα-atom of a non-terminal amino acid by a group--A which is defined in claim 1. The native α-side chain of the Cα atom bonded group to group --A absent. The peptide derivatives according
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- Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I
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Acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14, from porcine kidney and the fungus Aspergillus) is broadly applicable enzymatic catalyst for the kinetic resolution of unnatural and rarely occuring α-amino acids.Its enantioselectivity for the hydrolysis of N-acyl L-α-amino acids is nearly absolute, yet it accepts substrates having a wide range of structure and functionality.This paper reports the initial rates of enzyme-catalyzed hydrolysis of over 50 N-acyl amino acids and analogues, the stabilities of the enzymes in aqueous and aqueous/organic solutions, and the effects of different acyl groups and metal ions on the rates of enzymatic hydrolysis.Eleven α-amino and α-methyl α-amino acids were resolved on a 2-29-g scale.Crude L- and D-amino acid products had generally >90percent ee.The utility of resolved amino acids as chiral synthons was illustrated by the preparation of (R)- and (S)-1-butene oxide and the diastereoselective (cis:trans, 7-8:1) iodolactonization of three 2-amino-4-alkenoic acid derivatives.
- Chenault, H. Keith,Dahmer, Juergen,Whitesides, George M.
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p. 6354 - 6364
(2007/10/02)
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