cas 31795-93-4, N-Benzyl-L-Proline | Articles data

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Conformational analysis and mu-opioid receptor affinity of short peptides, endomorphin models in a low polarity solvent.
Peptide carbamates containing the sequence H-Pro-Trp-PheNH2 showed in CDCl3 restricted conformations stabilized by the presence of a gamma-turn. To test the reliability of the peptides as endomorphin conformational models, we measured the affinities for mu-receptors labelled with [3H]-DAMGO. In particular, Cbz-Pro-Trp-PheNH2 displayed a nanomolar affinity.
Cardillo, Giuliana,Gentilucci, Luca,Tolomelli, Alessandra,Qasem, Ahmed R,Spampinato, Santi,Calienni, Maria
p. 3010 - 3014
(2003)
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Selective N-benzylation of amino acids under homogeneously catalyzed hydrogenation conditions
The chemoselective N-benzylation of the α-amino acids L-proline, L-serine and L-threonine is described using a reductive amination procedure with benzaldehyde catalyzed by homogeneous Rh-complexes affording N-benzyl protected amino acids.
Tararov, Vitali I.,Kadyrov, Renat,Fischer, Christine,B?rner, Armin
p. 1961 - 1962
(2004)
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Improved synthesis of proline-derived Ni(II) complexes of glycine: Versatile chiral equivalents of nucleophilic glycine for general asymmetric synthesis of α-amino acids
A synthetically practical and operationally convenient method for preparing (S)-2-[N-(N′-benzylprolyl)-amino]benzophenone (BPBP) and hitherto unknown (S)-2-[N-(N′-benzylprolyl)amino]-4-methylbenzophenone (4-Me-BPBP), (S)-2-[N-(N′-benzylprolyl)amino]-5-nitrobenzophenone (5-NO2-BPBP), and their corresponding Ni(II) complexes with glycine [GlyNi(II)BPBP], a widely used chiral equivalent of nucleophilic glycine, and new analogues [GlyNi(II)-4-Me-BPBP] and [GlyNi(II)-5-NO2-BPBP] is described. The key step of the method is the synthetically efficient amid bond formation between the corresponding o-aminobenzophenones, featuring significant steric shielding and low nucleophilicity of the amino functionality as well as sterically constrained (S)-N-benzylproline (BP).
Ueki, Hisanori,Ellis, Trevor K.,Martin, Collin H.,Boettiger, Tomas U.,Bolene, Shawna B.,Soloshonok, Vadim A.
p. 7104 - 7107
(2003)
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l -Proline as a Valuable Scaffold for the Synthesis of Novel Enantiopure Neonicotinoids Analogs
In this research, six neonicotinoid analogs derived from l-proline were synthesized, characterized, and evaluated as insecticides against Xyleborus affinis. Most of the target compounds showed good to excellent insecticidal activity. To the best of our knowledge, this is the first report dealing with the use of enantiopure l-proline to get neonicotinoids. These results highlighted the compound 9 as an excellent candidate used as the lead chiral insecticide for future development. Additionally, molecular docking with the receptor and compound 9 was carried out to gain insight into its high activity when compared to dinotefuran. Finally, the neurotoxic evaluation of compound 9 showed lower toxicity than the classic neonicotinoid dinotefuran.
Bonilla-Landa, Israel,Cuapio-Mu?oz, Ulises,Luna-Hernández, Axel,Reyes-Luna, Alfonso,Rodríguez-Hernández, Alfredo,Ibarra-Juarez, Arturo,Suarez-Mendez, Gabriel,Barrera-Méndez, Felipe,Caram-Salas, Nadia,Enríquez-Medrano, J. Francisco,Díaz De León, Ramón E.,Olivares-Romero, José Luis
p. 1455 - 1465
(2021/02/16)

Preparation of labeled aromatic amino acids: Via late-stage18F-fluorination of chiral nickel and copper complexes
A general protocol for the preparation of 18F-labeled AAAs and α-methyl-AAAs applying alcohol-enhanced Cu-mediated radiofluorination of Bpin-substituted chiral complexes using Ni/Cu-BPX templates as double protecting groups is reported. The chiral auxiliaries are easily accessible from commercially available starting materials in a few synthetic steps. The versatility of the method was demonstrated by the high-yielding preparation of a series of [18F]F-AAAs and the successful implementation of the protocol into automated radiosynthesis modules. This journal is
Craig, Austin,Kolks, Niklas,Urusova, Elizaveta A.,Zischler, Johannes,Brugger, Melanie,Endepols, Heike,Neumaier, Bernd,Zlatopolskiy, Boris D.
supporting information
p. 9505 - 9508
(2020/09/03)

Synthesis of Chiral Spin-Labeled Amino Acids
Spin-labeled amino acids (SLAAs) are often used to determine intermolecular distances and conformations in proteins via double electron-electron resonance. Currently available SLAAs can be difficult to incorporate selectively and have little resemblance to natural side chains in proteins. Enantioselective synthesis of three spin-labeled l-amino acids is described, starting from readily available 2,2,6,6-tetramethyl-4-piperidinone. These SLAAs better replicate canonical residues in proteins and aim for biological incorporation via genetic incorporation or solid-phase peptide synthesis.
Vuong, Wayne,Mosquera-Guagua, Fabricio,Sanichar, Randy,McDonald, Tyler R.,Ernst, Oliver P.,Wang, Lei,Vederas, John C.
supporting information
p. 10149 - 10153
(2019/12/24)

Catalytic Transfer Hydrodebenzylation with Low Palladium Loading
A highly-efficient catalytic system for hydrodebenzylation reaction is described. The cleavage of O-benzyl and N-benzyl protecting groups was performed using an uncommonly low palladium loading (0.02–0.3 mol%; TON up to 5000) in a relatively short reaction time. The approach was used for a variety of substrates including pharmaceutically important precursors, and gram-scale deprotection reaction was shown. Transfer conditions together with easy-to-make Pd/C catalyst are the key features of this debenzylation scheme. (Figure presented.).
Yakukhnov, Sergey A.,Ananikov, Valentine P.
supporting information
p. 4781 - 4789
(2019/09/16)

N-ALKYLATED AMINO ACIDS AND OLIGOPEPTIDES, USES THEREOF AND METHODS FOR PROVIDING THEM.
The invention relates to the synthesis of amphiphilic amino acid derivatives, in particular to a method for the N-alkylation of an unprotected amino acid or the N-terminus of an oligopeptide substrate, comprising reacting said unprotected amino acid or oligopeptide substrate with an alcohol, e.g. a fatty alcohol, in the presence of a homogeneous transition metal catalyst.
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Page/Page column 17-19; 26; 28-31; 42; 43

(2018/10/25)

Rational Design and Synthesis of Modified Teixobactin Analogues: In Vitro Antibacterial Activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa
Teixobactin, a recently discovered depsipeptide that binds to bacterial lipid II and lipid III, provides a promising molecular scaffold for the design of new antimicrobials. Herein, we describe the synthesis and antimicrobial evaluation of systematically modified teixobactin analogues. The replacement of the Ile11 residue with aliphatic isosteres, the modification of the guanidino group at residue 10 and the introduction of a rigidifying residue, that is, dehydroamino acid, into the macrocyclic ring generated useful structure–activity information. Extensive antimicrobial susceptibility assessment against a panel of clinically relevant Staphylococcus aureus and Propionibacterium acnes strains led to the identification of the new lead compound, [Arg(Me)10,Nle11]teixobactin, with an excellent bactericidal activity (minimum inhibitory concentration (MIC)=2–4 μg mL?1). Significantly, the antimicrobial activity of several of the teixobactin analogues against the pathogenic Gram-negative Pseudomonas aeruginosa was “restored” when combined with the sub-MIC concentration of the outer membrane-disruptive antibiotic colistin. The antimicrobial effectiveness of a [Tfn10,Nle11]teixobactin (32 μg mL?1)–colistin (2 μg mL?1; 0.5×MIC) combination against P. aeruginosa PAO1 reveals, for the first time, an alternative therapeutic option in the treatment of Gram-negative infections.
Ng, Vivian,Kuehne, Sarah A.,Chan, Weng C.
supporting information
p. 9136 - 9147
(2018/06/29)

Discovery of novel n-substituted prolinamido indazoles as potent rho kinase inhibitors and vasorelaxation agents
Inhibitors of Rho kinase (ROCK) have potential therapeutic applicability in a wide range of diseases, such as hypertension, stroke, asthma and glaucoma. In a previous article, we described the lead discovery of DL0805, a new ROCK I inhibitor, showing potent inhibitory activity (IC50 6.7 μM). Herein, we present the lead optimization of compound DL0805, resulting in the discovery of 24- and 39-fold more-active analogues 4a (IC50 0.27 μM) and 4b (IC50 0.17 μM), among other active analogues. Moreover, ex-vivo studies demonstrated that 4a and 4b exhibited comparable vasorelaxant activity to the approved drug fasudil in rat aortic rings. The research of a preliminary structure-activity relationship (SAR) indicated that the target compounds containing a β-proline moiety have improved activity against ROCK I relative to analogues bearing an β-proline moiety, and among the series of the derivatives with a β-proline-derived indazole scaffold, the inhibitory activity of the target compounds with a benzyl substituent is superior to those with a benzoyl substituent.
Yao, Yangyang,Li, Renze,Liu, Xiaoyu,Yang, Feilong,Yang, Ying,Li, Xiaoyu,Shi, Xiang,Yuan, Tianyi,Fang, Lianhua,Du, Guanhua,Jiao, Xiaozhen,Xie, Ping
(2017/11/07)

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands
Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L-threonine, (2S, 3R)-L-CF3-threonine and (2S, 3S)-L-CF3-threonine were prepared. The capacity of (2S, 3S)- and (2S, 3R)-CF3
Xu, Yaochun,Correia, Isabelle,Ha-Duong, Tap,Kihal, Nadjib,Soulier, Jean-Louis,Kaffy, Julia,Crousse, Beno?t,Lequin, Olivier,Ongeri, Sandrine
supporting information
p. 2842 - 2853
(2018/01/17)

Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.
van Greunen, Divan G.,Cordier, Werner,Nell, Margo,van der Westhuyzen, Chris,Steenkamp, Vanessa,Panayides, Jenny-Lee,Riley, Darren L.
p. 671 - 690
(2017/02/10)

TRIAZOLE MACROCYCLE SYSTEMS
The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production.
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Paragraph 0271

(2016/02/22)

Asymmetric synthesis of α-amino acids under operationally convenient conditions
A new multipurpose glycine equivalent for the general asymmetric synthesis of α-amino acids is introduced. The chiral reagent can be transformed to various amino acids by alkylations with alkyl halides as well as aldol and Michael addition reactions under operationally convenient reaction conditions at room temperature with virtually complete stereochemical control.
J?rres, Manuel,Chen, Xia,Ace?a, José Luis,Merkens, Carina,Bolm, Carsten,Liu, Hong,Soloshonok, Vadim A.
supporting information
p. 2203 - 2208
(2014/07/21)

The formation of pyrroline and tetrahydropyridine rings in amino acids catalyzed by pyrrolysine synthase (PylD)
The dehydrogenase PylD catalyzes the ultimate step of the pyrrolysine pathway by converting the isopeptide L-lysine-Nε-3R-methyl-D-ornithine to the 22nd proteinogenic amino acid. In this study, we demonstrate how PylD can be harnessed to oxidize various isopeptides to novel amino acids by combining chemical synthesis with enzyme kinetics and X-ray crystallography. The data enable a detailed description of the PylD reaction trajectory for the biosynthesis of pyrroline and tetrahydropyridine rings as constituents of pyrrolysine analogues.
Quitterer, Felix,Beck, Philipp,Bacher, Adelbert,Groll, Michael
p. 8150 - 8153
(2014/08/18)

Optically active imidazole N-oxides derived from l-prolinamine1
Starting with (S)-1-benzylprolinamine and α-hydroxyimino ketones, enantiomerically pure bisheterocyclic imidazole N-oxides bearing the (S)-configured N-benzyl(pyrrolidin-2-yl)methyl residue were prepared. These N-oxides reacted with 2,2,4,4-tetramethylcyclobutane-1,3-dithione to give the corresponding optically active imidazole-2-thione derivatives via a sulfur transfer reaction. Reduction of the N-oxides with Raney-nickel led to deoxygenation, whereas catalytic hydrogenation (Pd/C) in ethanol occurred with simultaneous deoxygenation and debenzylation, leading to optically active 1-(pyrrolidin-2-yl)methyl-1H-imidazoles. Alkylation of the prepared imidazole N-oxides and their respective imidazoles with butyl and hexyl bromide and subsequent anion exchange gave optically active N-alkoxy- and N-alkylimidazolium tetrafluoroborates, respectively, with the properties of 'room temperature ionic liquids'.
Mloston, Grzegorz,Wroblewska, Aneta,Obijalska, Emilia,Heimgartner, Heinz
p. 958 - 965
(2013/09/23)

Enhanced stereoselectivity of a Cu(II) complex chiral auxiliary in the synthesis of Fmoc-L-γ-carboxyglutamic acid
L-γ-Carboxyglutamic acid (Gla) is an uncommon amino acid that binds avidly to mineral surfaces and metal ions. Herein, we report the synthesis of N-R-Fmoc-L-γ-carboxyglutamic acid γ, γ0-tert-butyl ester (Fmoc-Gla(OtBu)2-OH), a suitably protected analogue for Fmoc-based solid-phase peptide synthesis. The residue was synthesized using a novel chiral Cu(II) complex, whose structurebased design was inspired by the blue copper protein rusticyanin. The five-coordinate complex is formed by Shiff base formation between glycine and the novel ligand (S)-2-(N-(2-methylthio)benzylprolyl) aminobenzophenone in the presence of copper. Michael addition of di-tert-butyl methylenemalonate to the R-carbon of the glycine portion of the complex occurs in a diastereoselective fashion. The resulting (S,S)-complex diastereomer can be easily purified by chromatography. Metal complex decomposition followed by Fmoc protection affords the enantiomerically pure amino acid. With the use of this novel chiral complex, the asymmetric synthesis of Fmoc-Gla(OtBu)2-OH was completed in nine steps from thiosalicylic acid in 14.5% overall yield.
Smith, Daniel J.,Yap, Glenn P.A.,Kelley, James A.,Schneider, Joel P.
supporting information; experimental part
p. 1513 - 1520
(2011/06/20)

BIS-BENZIMIDAZOLE DERIVATIVES AS HEPATITIS C VIRUS INHIBITORS
Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R and R' have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.
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Page/Page column 22

(2011/02/24)

NOVEL CYCLIC BORONATE INHIBITORS OF HCV REPLICATION
Compounds of formula (I) or a salt thereof are provided; wherein R1, R2, R3, R4, R6, R8, R20, R30, Y, Z and n are as defined in the description. Uses of the compounds as medicaments, and in the manufacture of medicaments for treating viral infection, especially HCV infection are also disclosed. The invention further comprises processes to make these compounds and pharmaceutical formulations thereof.
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Page/Page column 73-75

(2009/05/29)

Asymmetric addition of terminal alkynes to n-(Diphenylphosphinoyl)imines promoted by stoichiometric amounts of a proline-derlved ss-amino alcohol
A new synthetic methodology for the preparation of optically active propargylamines is described. The alkynylation of aromatic, heteroaromatic, aliphatic and α,β-unsaturated N-(di-phenylphosphinoyl)imines was investigated by using dieth-ylzinc and a proline-derived β-amino alcohol, N-(Diphenylphosphinoyl)-protected propargylic amines can be synthesized in high yields and with good to excellent: enantio-selectivities.
Yan, Wenjin,Mao, Bin,Zhn, Shaoqun,Jiang, Xianxing,Liu, Zhongli,Wang, Rui
supporting information; experimental part
p. 3790 - 3794
(2009/12/07)

Preparation and conformational study of CF3-containing enkephalin-derived oligopeptide
Incorporation of (2S,3S)-4,4,4-trifluorothreonine (F3-Thr) instead of Thr in the enkephalin-derived hexapeptide led to the apparent conformational alteration due to the strong electron-withdrawing effect of the trifluoromethyl group by comparison with the original compound on the basis of their various NMR measurements.
Kitamoto, Takamasa,Marubayashi, Shunsuke,Yamazaki, Takashi
p. 1888 - 1894
(2008/09/18)

Enantioselective Michael addition of dicyanoolefins to α,β- unsaturated aldehydes in aqueous medium
A pool of water-compatible catalysts, namely dialkyl-(S)-prolinols, has been developed for the enantioselective direct vinylogous Michael addition reaction of vinylmalononitriles to α,β-unsaturated aldehydes in aqueous medium. In many cases, the products can be obtained in almost optically pure form (>96% ee) after a single recrystallization.
Lu, Jun,Liu, Feng,Loh, Teck-Peng
supporting information; experimental part
p. 1781 - 1784
(2009/07/10)

A novel method for the synthesis of chiral epoxides from styrene derivatives using chiral acids in presence of Pseudomonas lipase G6 [PSL G6] and hydrogen peroxide
Chiral epoxidation of styrene and its derivatives was carried out using series of chiral acids and urea hydrogen peroxide (UHP) or aqueous hydrogen peroxide (50%) in two phases under the catalytic influence of immobilized Pseudomonas lipase G6 [PSL G6] at 25-55 °C. A moderate to good yield and enantioselectivities of chiral epoxides were obtained.
Sarma, Kuladip,Bhati, Nishi,Borthakur, Naleen,Goswami, Amrit
p. 8735 - 8741
(2008/02/09)

Proline-based N-oxides as readily available and modular chiral catalysts. Enantioselective reactions of allyltrichlorosilane with aldehydes
(Chemical Equation Presented) A proline-based N-oxide is identified that serves as an effective catalyst for the reaction of allyltrichlorosilane with aryl and α,β-unsaturated aldehydes at room temperature to afford the desired homoallylic alcohols in up to 92% ee. The chiral catalyst can be easily prepared from optically pure proline in three simple steps and 60% overall yield.
Traverse, John F.,Zhao, Yu,Hoveyda, Amir H.,Snapper, Marc L.
p. 3151 - 3154
(2007/10/03)

VLA-4 inhibitor compounds
Compounds that selectively inhibit the binding of ligands to alpha4beta1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.
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(2008/06/13)

Carbapenem biosynthesis: Confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-Proline
(5R)-Carbapen-2-em-3-carboxylic acid is the simplest structurally among the naturally occurring carbapenem β-lactam antibiotics. It co-occurs with two saturated (3S,5S)- and (3S,5R)-carbapenam carboxylic acids. Confusion persists in the literature about t
Stapon, Anthony,Li, Rongfeng,Townsend, Craig A.
p. 8486 - 8493
(2007/10/03)

Mapping the substrate selectivity of new hydrolases using colorimetric screening: Lipases from Bacillus thermocatenulatus and Ophiostoma piliferum, esterases from Pseudomonas fluorescens and Streptomyces diastatochromogenes
Recent advances in biochemistry and molecular biology have simplified the discovery and preparation of new hydrolases. Although these hydrolases might solve problems in organic synthesis, measuring their selectivity, especially enantioselectivity, remains tedious and time consuming. Recently, we developed a colorimetric screening method to measure the enantioselectivity of hydrolases. Here we apply this rapid screening method to map the substrate selectivity of four new hydrolases: lipases from the thermophilic Bacillus thermocatenulatus (DSM 730, BTL2) and a filamentous fungus Ophiostoma piliferum (NRRL 18917, OPL) and esterases from two bacteria, Pseudomonas fluorescens (SIK-W1, esterase I, PFE) and Streptomyces diastatochromogenes (Tue 20, SDE). We screened a general library of 29 substrates and a chiral library of 23 pairs of enantiomers. All four hydrolases catalysed the hydrolysis of unnatural substrates, but the two lipases accepted a broader range of substrates than the two esterases. As expected, the two lipases favoured more hydrophobic substrates, while the two esterases showed a preference for smaller substrates. Several moderately enantioselective reactions were identified for the solketal esters: BTL2, butyrate, E = 7.9 (R); octanoate, E = 4.9 (R) and 3-bromo-2-methyl propionate methyl esters, PFE, E = 12 (S); SDE, E = 5.6 (S). OPL showed low enantioselectivity toward all substrates tested. The current colorimetric screen could not measure the selectivity for several slow-reacting substrates. Traditional screening identified high enantioselectivity of BTL2 and PFE toward one of these slow substrates, 1-phenylethyl acetate (E>50).
Liu, Andrew Man Fai,Somers, Neil A.,Kazlauskas, Romas J.,Brush, Terry S.,Zocher, Frank,Enzelberger, Markus M.,Bornscheuer, Uwe T.,Horsman, Geoff P.,Mezzetti, Alessandra,Schmidt-Dannert, Claudia,Schmid, Rolf D.
p. 545 - 556
(2007/10/03)

Improved procedures for the synthesis of (S)-2-[N-(N'-benzyl- prolyl)amino]benzophenone (BPB) and Ni(II) complexes of Schiff's bases derived from BPB and amino acids
(S)-N-Benzylproline (BP) was obtained by the reaction of (S)-proline and benzylchloride in high chemical yield (89%). (S)-2-[N-(N'- Benzylprolyl)amino]benzophenone (BPB) was synthesized in amounts greater than 100 g by the SOCl2 promoted condensation of BP with 2-aminobenzophenone (yield 82%). Ni(II) complexes of Schiff's bases derived from BPB and amino acids were prepared by an improved procedure involving the use of KOH as a base and MeOH as solvent (yield 90-91%).
Belokon', Yuri N.,Tararov, Vitali I.,Maleev, Viktor I.,Savel'eva, Tatiana F.,Ryzhov, Michael G.
p. 4249 - 4252
(2007/10/03)

Solid phase reductive alkylation of secondary amines
Solid phase reductive alkylation of secondary amines has been carried out in excellent yields using borane-pyridine complex (BAP). Various aldehydes and ketones have been reacted with L-proline substituted on high-capacity Wang Resin.
Khan, Nawaz M.,Arumugam, Vijayalakshmi,Balasubramanian, Shankar
p. 4819 - 4822
(2007/10/03)

The First Enantioselectice Total Syntheses of the Allopumiliotoxin A Alkaloids 267A and 339B
Short, highly stereocontrolled, asymmetric total syntheses of the title amphibian alkaloids are described.In the first stage the indolizidine ketone 11 is assembled from L-proline in enantiomerically pure form.This short sequence proceeds in five laborato
Goldstein, Steven W.,Overmann, Larry E.,Rabinowitz, Michael H.
p. 1179 - 1190
(2007/10/02)

Asymmetric Synthesis of Threonine and Partial Resolution and Retroracemization of α-Amino Acids via Copper(II) Complexes of Their Schiff Bases with (S)-2-N-(N'-Benzylprolyl)aminobenzaldehyde and (S)-2-N-(N'-Benzylprolyl)aminoacetophenone. Crystal and Molecular Structure of a ...
The work described here is concerned with the search for universal chiral reagent for the asymmetric synthesis, resolution, and retroracemization of amino acids.Reaction of N-benzyl-(S)-proline with o-aminobenzaldehyde or o-aminoacetophenone has given (S)-2-N-(N'-benzylprolyl)aminobenzaldehyde ((S)-BPAB) or (S)-2-N-(N'-benzylprolyl)aminoacetophenone ((S)-BPAAPh).These chiral reagents have interacted with α-amino acids (aa) and Cu(II) ions to form complexes CuII and CuII in which Schiff bases (S)-BPAB-aa or (S)-BPAAPh-aa act as tetradentate ligands and coordinate the copper ion by the nitrogen atoms of the pyrrolidine fragment, the deprotonated amide group, and the amino acid fragment and by the oxygen atom of the carboxylate.Such a structure was supported by data on elemental analysis, the molecular weight measurements, and electron, IR, and CD spectra.It was finally confirmed by an X-ray diffraction analysis of CuII.One equivalent of (S)-BPAB has reacted with 2 equiv of (R,S)-aa and 2 equiv of Cu(II), having given preferential formation of copper complexes of Schiff bases with (S)-aa.After their extraction with chloroform the amino acid enriched with the R enantiomer remained in the aqueous solution.In this manner partial resolution of racemic amino acids (Ala, Nva, Phe, Val, Thr) has been carried out with enantiomeric purity 4-50percent. (S)-BPAB or (S)-BPAAPh treatment of a racemic amino acid in the presence of Cu(II) ions (reagents ratio 1:1:1) and CH3O- ions permits enantiomeric enrichment via conversion of the R into S enantiomer (retroracemization).Thus (S)-Ala, (S)-Nva, (S)-Leu, (S)-Val, (S)Phe, and (S)-PhGly of enantiomeric purity 36, 12, 22, 54, 42, and 35percent, respectively, were obtained from racemic samples.CH3O--catalyzed reaction of CuII or CuII with acetaldehyde has given rise to a mixture of diastereomeric complexes, which upon removal of Cu(II) by H2S gave (R)-threonine of 60percent or 97-100percent enantiomeric purity and the threo/allo ratio 6:1 or 19:1, respectively, and permitted recovery of an unchanged initial chiral reagent (S)-BPAB or (S)-BPAAPh.
Belokon', Yu. N.,Zel'tzer, I. E.,Bakhmutov, V. I.,Saporovskaya, M. B.,Ryzhov, M. G.,et al.
p. 2010 - 2017
(2007/10/02)