Enantioselective Hydrolysis of α-Amino Acid Ester by Chiral Metallomicelles

Metall0ndcellesmadeup0ffunctionalizedsurfactants(orliP0philicligands)caPable0feffectivechelationofmetalionsarecurrentlyreceivingc0nsiderableinterestbecauseoftheircatalyticabilitytomindcmetall0enzymes.OfpatticularinterestarethendcellarmodelsofhydrolghcmetalloenZyInes,whichareabletoprom0tethecleavageofphosphoricandcarboxylicesters0raAndes.'-'M0stofthemaref0cused0ntheligandscontainingidridazole',pyridine'orl,lO-phenanthroline'asthebasicchelatingsubunitandasthem0lecularjunctionfortheparaffmiccha…     

The Simple Synthesis of Chiral Polyazaoxacoronands Derived from α-Amino Acids

Abstract

Bisamidation of oxaloyl chloride using L-amino acid methyl ester hydrochlorides afforded chiral diesters. The following reactions of diesters with 2,2-(ethylene-dioxy)diethylamine, afforded tetramides possessing C₂ symmetry. Coupling of N-hydroxysuccinimide ester of N-benzyloxycarbonyl-L-alanine with 1,5-diamino-3-oxapentane, followed by cleavage of protecting groups, afforded an optically active diamine, which was transformed consequently into tetramide via the reaction with diglycolic acid dimethyl ester under high pressure conditions.     

Enzymatic Resolution of α-Amino Phosphonous Acids -A Kinetic Comparison with Other α-Amino Acids Using 19F and 31P NMR Analysis

Abstract

We have previously reported (1,) the synthesis of a range of α-aminophosphonous acids and found them to be mimics of the naturally occurring amino acids. They inhibit the protein synthesis of E.Coli B (2) and other synthetases (3). We have now found that such compounds can be conveniently resolved via their N-acyl derivatives by enzymatic methods. Using penicillin-G-amidase from E.Coli (EC 3.5.1.11) the R-enantiomer is cleanly hydrolysed leaving the S-enantiomer intact.     

Diastereoselective α-Alkylation of β-Amino Esters: Preparation of Novel α-Substituted β-Amino Esters from α-Amino Acids

b-Amino acids and their derivatives have attracted considerable attention in recent years due to their occurrence in biologically active natural products, such as dolastatins 11, cyclohexylnorstatine 22 and taxol 33. bAmino acids also find application in the synthesis of blactams4, piperidines5, indolizidines6. Moreover, the peptides consisting of bamino acids, the so called bpeptides, have been extensively studied recently7. Consequently, considerable efforts have been directed to the synt…     

Synthesis of a New Chiral Cyclicβ-Amino Alcohol

The enantioselective chiral l,3,2-oxazaborolidine-catalyzed reduction of prochiralketones by borane has been intensively investigated'-'. Most oxazaborolidine catalystshave been prepared from chiral D-amino alcohols. In our previous study on the catalyststructure-enantioselectivity relationships, we prepared (R)-2-amino-1,l-diphenyl-3~(2naphthyl)-l-propanol I which proved to be a good precursor of chiral catalyst for theenantioselective borane reduction of prochiral ketones4-9. This let'ter d…     

Iodine-catalyzed Synthesis of α-Amino Phosphonates

α-Amino phosphonates are structural analogues of the corresponding α-amino acids. They are found to exhibit intriguing biological activities1, for example as enzyme inhibitors, peptidomimetics, antibacterial agents and other pharmacological agents. A va…     

Liquid Chromatorgraphic Separation of the Enantiomers of Phenylthiohydantoin α-Amino Acids Derivatives on Polysaccharide-Based Chiral Stationary Phases

ABSTRACT

The liquid chromatographic enantioseparation of the phenylthiohydantoin (PTH) derivatives of various amino acids on four commercial polysaccharide-derived chiral stationary phases (CSPs) is described. Chiralcel OF and Chiralpak AS showed better performance than the other CSPs for resolution of the enantiomers of PTH amino acid derivatives. The enantiomers of all amino acids as their PTH derivatives were well separated on Chiralcel OF and/or Chiralpak AS. The (-)(L) or (-)-enantiomers of all analytes examined were preferentially retained on Chiralpak AS, whereas the (+)(D) or (+)-enantiomers of most of analytes were preferentially retained on Chiralcel OF.     

Synthesis of Chiral Benzofuran-Derived β-Amino Esters Induced by N-tert-Butanesulfinamide

The benzofuran skeleton is commonly found in a wide variety of natural products that display a wide range of biological activities. For this reason, benzofuran has a high potential for use as a scaffold in both chemical and pharmaceutical syntheses of natural products. This work describes the development of a novel asymmetric synthetic method of benzofuran-derived β-amino esters via K₂CO₃-promoted domino reactions of ortho-hydroxyl aromatic N-tert-butylsulfinyl imines and diethyl bromomalonate. A small library of target compounds was prepared under optimized reaction conditions in moderate to good yields with high distereoselective and enantioselective properties. The newly generated chiral carbon center was of an (S)-configuration as determined by x-ray diffraction.     

Enantio- and Diastereoselective Synthesis of Chiral Tetrasubstituted α-Amino Allenoates Bearing a Vicinal All-Carbon Quaternary Stereocenter with Dual-Copper-Catalysis

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are of importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions of 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording chiral tetrasubstituted α-amino allenoates bearing a vicinal all-carbon quaternary stereocenter in high yields (up to 99 % yield) with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to >20 : 1 dr). Importantly, the stereodivergent synthesis of the products was realized by the asymmetric γ-addition reaction and the Grignard reagent promoted epimerization. Moreover, the dual-copper-catalyzed γ-addition reactions were smoothly applied to a gram-scale reaction and adopted to introduce chiral tetrasubstituted allenyl moieties into bioactive molecules. Mechanistic experiments and density functional theory (DFT) calculations demonstrated that the asymmetric γ-addition reactions were catalyzed by double chiral copper catalysts.     

Asymmetric Synthesis of Perfluoroalkylated α-Amino Acids through Generated Radicals Using a Chiral Ni(II) Complex

Perfluoroalkylated α-amino acids (PFAAs) are a unique class of compounds for biochemistry and pharmaceutical science. In this context, we report the successful intermolecular coupling of the Belokon’s chiral dehydroalanine Ni(II) complex with a variety of perfluoroalkyl iodides. A 4-cyanopyridine/B₂Pin₂ catalytic system generates perfluoroalkyl radicals, which after trapping by the ligand sphere of a chiral Ni(II) complex provide the diastereomeric complexes with up to >20 : 1 dr (seven examples). The obtained major (S,S)-diastereomers were easily isolated by simple silica column chromatography in 33–54 % yields. The perfluoroalkylated α-AA was subsequently released from the obtained Ni(II) complex through aqueous HCl treatment. The chiral auxiliary ligand ((S)-BPB=(S)-2-(N-benzylprolyl)aminobenzophenone) can be easily recycled after the acidic complex decomposition and reused for the synthesis of the starting dehydroalanine Ni(II) complex.     

Effect of Temperature on The Solubility of α-Amino Acids and α,ω-Amino Acids in Water

The aqueous solubilities of glycine, dl-α-alanine (2-aminopropanoic acid), dl-α-aminobutyric acid (2-aminobutanoic acid), dl-α-norvaline (2-aminopentanoic acid), dl-α-norleucine (2-aminohexanoic acid), β-alanine (3-aminopropanoic acid), γ-aminobutyric acid (4-aminobutanoic acid), 5-aminovaleric acid (5-aminopentanoic acid), and 6-aminocaproic acid (6-aminohexanoic acid) were determined from 293.15 to 323.15 K at intervals of 5.00 K using the gravimetric method. The temperature dependence of the solubility of α-amino acids and α,ω-amino acids in water is well described by the van’t Hoff equation. Linear van’t Hoff plots were used to determine the differential enthalpy of solution. The results obtained are compared with reported values in literature and are discussed in terms of the position of the ionic groups in the hydrocarbon chain.     

Diastereoselective Synthesis of Rotationally Restricted Chiral Phenylpyridines via Intramolecular Cascade Cyclization of N-Acyliminium Ions Containing α-Amino Acid Residues

A series of chiral phenylpyridines possessing a fused chiral bridge were synthesized diastereoselectively via cascade cyclizations, where N-acyliminium ions including an enantiopure α-amino acid residue were involved. The absolute configuration of the synthesized phenylpyridines was identified unambiguously by using nuclear Overhauser effect difference and circular dichroism (CD) measurements on the basis of literature methods.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications^® for the following free supplemental resources: Full experimental and spectral details.]     

Soluble Polymer-Supported Synthesis of α-Amino Acid Derivatives

Due to the central role played by α-amino acid in chemistry and biology, the development of versatile and new methodology for the synthesis of natural and unnatural α-amino acid has emerged as an important and challenging synthetic endeavour for organic chemists.[1] Among the various methodologies reported for α-amino acid synthesis, [2,3] the solid-phase organic synthesis (SPOS) has served as an important approach. [4] However, inherent prob lems on solid supports are reactive site accessibility, site-site interaction and monitoring of the reaction.     

Membrane Transport of the Zwitterionic Aromatic α-Amino Acids by α-Aminophosphonates

Abstract

Bghly selective biological transport of amino acids is usually mediated by carrier proteins. The application of such membrane systems for the analysis and separation of amino acids has long studied. This work is devoted to the transport of zwitterionic form of aromatic a-amino acids such as d,l-Phe, d,l-DOPA, d,l-His, d,l-Tyr, d,l-Trp, via supported liquid membrane (SLM). The lipophilic α-aminophosphonates (I).

R₁ amyl or 2-ethylhexyl; R₂, R₂-(CH₂)4-(CH₂)5-CH₃ & (CH₃), C₄ H(CH₉) & H; H & H; have been used as carrier in the membrane systems composed of a porous polymeric support (Millipore Type FA) impregnated with 10^?1 M carrier in o-nitrophenyl n-octyl ether (amino acid concentration in source phase is 10^?3 M). The cell for membrane extractions is presented on Fig I.     

Anti-Markovnikov Hydroamination of Racemic Allylic Alcohols to Access Chiral γ-Amino Alcohols

A ruthenium-catalyzed formal anti-Markovnikov hydroamination of allylic alcohols for the synthesis of chiral γ-amino alcohols is presented. Proceeding via an asymmetric hydrogen-borrowing process, the catalysis allows racemic secondary allylic alcohols to react with various amines, affording enantiomerically enriched chiral γ-amino alcohols with broad substrate scope and excellent enantioselectivities (68 examples, up to >99 % ee).     

Synthesis of Boc-Amino Tetrazoles Derived from α-Amino Acids

A simple route for the synthesis of Boc-protected tetrazole analogs of amino acids starting from N ^α-Boc amino acids has been described. The [2 + 3] cycloaddition of Boc-α-amino nitrile and sodium azide in the presence of a catalytic amount of zinc bromide yielded the desired tetrazoles in good yields and purity. All the compounds obtained have been characterized by ¹H and ¹³C-NMR and mass spectral studies.     

Syntheses of α-Amino Phosphinic Acids via Oxo-iminium Salts

Nitrones 2a , 2b obtained from the aldehydes 1a , 1b , are used for the syntheses of the N-ethoxy iminium salts 4a and 4b . In the following procedure 4a and 4b react to several esters of phosphinic acids 6a - 6d .     

Recognition of α-Amino Acid from β- and γ-Amino Acid by N -Phosphorylation

The reactivity of N -phosphoryl f -alanine differs from N -phosphoryl g -alanine and N -phosphoryl n -amino butyric acid enormously. N -phospho- f -alanine could self-activate to yield N -phosphopeptides either in aqueous or nonaqueous media, but not g - or n -amino acid analogues. The mechanism of the reaction is discussed.