First stereocontrolled synthesis of (S)-cleonin and related cyclopropyl-substituted amino acids

[reaction: see text]. Enantiomerically pure (S)-cleonin, a key component of the antitumor antibiotic cleomycin, was prepared starting from (R)-serine. The Kulinkovich cyclopropanation of the methyl ester of N-Cbz serine acetonide gave the hydroxycyclopropyl moiety. The amino alcohol region was further oxidized to amino acid. The Kulinkovich cyclopropanation allowed also the preparation of other non-natural substituted cyclopropylglycines.     

Unnatural benz-X-azolyl asparagine derivatives as novel fluorescent amino acids: synthesis and photophysical characterization

A family of new asparagine derivatives bearing benzothiazole and benzimidazole units, functionalised with electron donor or acceptor groups, were synthesized in good to excellent yields. The photophysical characterization of these new heterocyclic amino acids was performed by UV-visible absorption and fluorescence emission studies and revealed that the compounds displayed remarkably high fluorescence quantum yields and Stokes' shifts, making them good candidates for application as fluorescent probes by incorporation into peptidic frameworks.     

Water-soluble zinc porphyrins as artificial receptors for amino acids

The binding of amino acids to water-soluble zinc porphyrins in basic aqueous solution was spectrophotometrically analyzed. The amino acids were bound to the porphyrins through the coordination of the N atom with the central zinc ion. Additional attractions arise due to Coulomb interactions between the -COO(-) anion of the amino acids and the -N(CH(3))(3)(+) cation of the porphyrin substituents and due to hydrophobic interactions between the porphyrin plane and the hydrophobic substituents of the amino acids. These attractions could be explained based on the binding data. The compensatory relationships of DeltaS and DeltaH were also discussed.     

Expedient copper-catalyzed borylation reactions using amino acids as ligands

Amino acids were found to be as good ligands for copper-catalyzed borylation reactions of primary and secondary alkyl halides,and the B2pin2 acted as bi-boron source for borylation.The high reaction efficiency and mild conditions make the new catalyst system a useful alternative to the recently developed methods for the preparation of alkylboronic esters.     

Fullerene-derivatized amino acids: synthesis, characterization, antioxidant properties, and solid-phase peptide synthesis

A series of [60]fullerene-substituted phenylalanine (Baa) and lysine derivatives have been prepared by the condensation of 1,2-(4'-oxocyclohexano)fullerene with the appropriately protected (4-amino)phenylalanine and lysine, respectively. Conversion of the imine to the corresponding amine is achieved by di-acid catalyzed hydroboration. The reduction of the imine is not accompanied by hydroboration of the fullerene cage. The [70]fullerene phenylalanine derivative has also been prepared as have the di-amino acid derivatives. The compounds were characterized by MALDI-TOF mass spectrometry, UV/Vis spectroscopy, and cyclic voltammetry. 1H and 13C NMR spectroscopy allowed the observation of diastereomers. Fullerene-substituted peptides may be synthesized on relatively large scale by solid-phase peptide synthesis. The presence of the C60-substituted amino acid in a peptide has a significant effect on the secondary structures and self-assembly properties of peptides as compared to the native peptide. The antioxidant assay of Baa and a Baa-derived anionic peptide was determined to be significantly more potent than Trolox.     

Synthesis and characterization of chiral iron carbonyl complexes from imine ligands with carbohydrates and amino acids as substituents

Imine ligands derived from 6-amino-6-desoxy-1,2,3-O-trimethyl--d-glucopyranose or from various amino acid esters react with Fe₂(CO)₉ to give chiral iron carbonyl complexes. Derivatives produced from benzaldehyde react via a C–H activation reaction in ortho-position with respect to the exocyclic imine substituent followed by an intramolecular hydrogen transfer reaction of the activated hydrogen towards the former imine carbon atom. The molecular structure of the diiron hexacarbonyl complexes of benzylideneamino-l-phenylalanine ethyl ester and benzylideneamino-l-methionine methyl ester were characterized by means of X-ray structure determinations. Imines produced from cinnamaldehyde upon reaction with Fe₂(CO)₉ produce mononuclear iron tricarbonyl complexes with the imine ligand being coordinated in a η⁴-fashion.     

Nonpeptidic foldamers from amino acids: synthesis and characterization of 1,3-substituted triazole oligomers

Nonpeptidic foldamers capable of displaying protein-like functionality were prepared by swapping amide bonds with 1,2,3-triazole rings. The overall conformation of these triazole oligomers is largely dictated by dipole-dipole interactions between adjacent rings. Solution NMR studies suggest that a zigzag conformation, which closely mimics the beta-strand structure, predominates in two different tetramers.     

Luminol chemiluminescence HPLC reaction detector for amino acids and other ligands

A detector for HPLC is based on suppression of chemiluminescence from the Cu(II)-luminol-peroxide reaction. Analytes which complex Cu(II) reduce the free Cu(II) concentration and thus the observed chemiluminescence intensity. The degree of chemiluminescence suppression is a measure of the analyte concentrations. Detection limits are in the range of 1 pmole-1 nmole for amino acids (both primary and secondary without derivatization), CN^–, amines, catecholamines, catechol, and aminoglycoside antibiotics. The detection approach is demonstrated with an ion-exchange separation of amino acids, a reverse phase separation of catecholamines, and an ion-pair separation of the three components of gentamicin C in commercial gentamicin sulfate.     

Abc amino acids: design, synthesis, and properties of new photoelastic amino acids

Photoisomerizable amino acids provide a direct avenue to the experimental manipulation of bioactive polypeptides, potentially allowing real-time, remote control of biological systems and enabling useful applications in nanobiotechnology. Herein, we report a new class of photoisomerizable amino acids intended to cause pronounced expansion and contraction in the polypeptide backbone, i.e., to be photoelastic. These compounds, termed Abc amino acids, employ a photoisomerizable azobiphenyl chromophore to control the relative disposition of aminomethyl and carboxyl substituents. Molecular modeling of nine Abc isomers led to the identification of one with particularly attractive properties, including the ability to induce contractions up to 13 A in the backbone upon trans --> cis photoisomerization. This isomer, designated mpAbc, has substituents at meta and para positions on the inner (azo-linked) and outer rings, respectively. An efficient synthesis of Fmoc-protected mpAbc was executed in which the biaryl components were formed via Suzuki couplings and the azo linkage was formed via amine/nitroso condensation; protected forms of three other Abc isomers were prepared similarly. An undecapeptide incorporating mpAbc was synthesized by conventional solid-phase methods and displayed characteristic azobenzene photochemical behavior with optimal conversion to the cis isomer at 360 nm and a thermal cis --> trans half-life of 100 min at 80 degrees C.     

Aziridines derived from amino acids as synthons in pseudopeptide synthesis

The reactivity of the Z-protected aziridine derived from aspartic acid has been studied with various N- and O-nucleophiles. The optimized reaction conditions allow quick and easy access to 1, 2-diamines or amino alcohols. In the case of opening with N-nucleophiles, very good regioselectivity was observed. Use of an α-amino ester as the nucleophile yielded a methyleneamino pseudodipeptide.     

Synthesis and pharmacological characterization at glutamate receptors of erythro- and threo-tricholomic acid and homologues thereof

The erythro- and threo-amino-(3′-hydroxy-4′,5′-dihydro-isoxazol-5′-yl)-acetic acids, stereoisomers of tricholomic acid, were synthesized along with the corresponding higher homologues erythro- and threo-amino-(3′-carboxy-4′,5′-dihydro-isoxazol-5′-yl)-acetic acids. The target compounds were prepared via the 1,3-dipolar cycloaddition of a suitable nitrile oxide to (±)-2-tert-butoxycarbonylamino-3-buten-1-ol. Such a strategy allowed the synthesis of the two stereoisomeric amino acids in comparable amounts. The pharmacological activity of these compounds was investigated at ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs) by means of receptor binding assays to rat cortical membranes, electrophysiological tests and second messenger assays at cloned receptors expressed in CHO cells. Their pharmacological profiles were compared to those of l-glutamate and of the previously described selective NMDA receptor antagonists 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acids in order to highlight the effect of increasing/reducing the distance between the amino acid moiety and the distal acid group, which represent the two pharmacophoric entities.     

HRGC of wine free amino acids as a tool for elementary wine characterization

In this paper we show that wine free amino acids derivatized as isopropyl N-heptafluorobutyryl esters can be used as a tool for wine characterization. Elementary wines of eight Vitis vinifera varieties were studied during a seven year period. The characteristic wine amino acids for each variety were assessed by means of pattern recognition techniques. A “star symbol plot” was used for graphic representation.     

Thiourea isosteres as anion receptors and transmembrane transporters

Compounds containing cyanoguanidine and 3-amino-1,2,4-benzothiadiazine-1,1-dioxide have been studied as anion receptors and transporters. Significant affinity for oxo-anions was observed in organic solution and the receptors were found to function as transmembrane chloride/nitrate antiporters with transport rates enhanced in the presence of valinomycin-K(+) complex.     

Luminescent silica nanobeads: characterization and evaluation as efficient cytoplasmatic transporters for T-lymphocytes

We report the fabrication and characterization of neutravidin-conjugated silica nanobeads doped with a ruthenium-complex luminophore and functionalized with antihuman CD3, antihuman CD28, and an acid-sensitive polymer. We observed that the nanobeads were readily delivered into Jurkat T leukemia cells by endocytosis, transported into lysosomes and subsequently into the cytoplasm as revealed by pH-sensitive luminescence. Since signs of cytotoxicity were not observed, the reported nanobeads could be an excellent and nontoxic building block for efficient intracellular transporters.     

Novel chiral fluorescent macrocyclic receptors: synthesis and recognition for amino acid anions

New chiral fluorescence macrocycles 1 and 2 containing naphthalene and amino acid units were synthesized. The binding properties for amino acid anions were examined by the fluorescence and ¹H NMR spectra. The results indicated good enantioselectivity of 1 toward the N-protected phenylalanine anions.     

Improved synthesis of unnatural amino acids for peptide stapling

The procedures for the synthesis of various α-alkenyl and alkyne amino acids were systematically optimized in light of enhancing atom economy, reducing hazardous reagent usage, and simplifying workup. By starting with Boc-Pro-OH and coupling with EDCI/DMAP followed by alkylation, chiral auxiliary was synthesized with high yield and enantioselectivity. For alkylation of the chiral complex, tBuONa was found and proved by quantitative calculation to be superior to tBuOK in generating more nucleophilic enolate salt, thereby can significantly enhance yield under room temperature. Final Fmoc protection was also dramatically facilitated in one-pot sequential manner by adding EDTA-2Na as the nickel chelator. Synthesis of α-bisalkenyl amino acid was also accomplished by achiral complex approach with high yield and efficacy. Accordingly, five most commonly used N-Fmoc protected α-alkenyl and alkynyl amino acids were synthesized and characterized.     

Polyphenols as superoxide dismutase modulators and ligands for estrogen receptors

The capacity of estrogen and stilbene derivatives to modulate the activity of superoxide dismutases in relation with their estrogenic properties has been studied. The properties of trans-resveratrol (3,5,4′-trihydroxystilbene) and its analogues, 4-hydroxystilbene, 4,4′-dihydroxystilbene, 3,5-dihydroxystilbene, 3,5,4′-trimethoxystilbene and 4,4′-dihydroxy-3,5,3′,5′-tetramethylstilbene were compared to 17β-estradiol and its analogues (2-methoxyestradiol, estrone, 2-hydroxyestradiol and 2-methoxyestrone). Measurement of estrogen receptor-β (ER-β) binding capacity was carried out by a receptor competitor assay associated with fluorescence polarisation detection. The superoxide dismutase (SOD) modulation activity was followed with a spectrophotometric assay using the sequence xanthine/xanthine oxidase-2,3-bis[2-methoxy-4-nitro-sulfo-phenyl]-2H-tetrazolium-5-carboxanilide (X/XO-XTT). The structure-activity relationship was different for the two series tested. In the estrogenic series, a compound which does not inhibit SOD, is recognized by the ER-β. In contrast for the stilbenic series both properties are parallel each other.