A Convenient Synthesis of β-Amino Acid

We have reported the reductive cleavage of azlactones¹ and phenylhydrazones² of carbonyl compounds in the presence of a suitable catalyst. In this paper a general method involving a one step synthesis of β-amino acid^3,4, in good yield, through catalytic reduction of oximes of α-β-unsaturated acid is reported. This method involves the reaction of α, β-unsaturated acid with hydroxylamine hydrochloride in the presence of sodium acetate. Markovnikov's rule is followed in the synthesis of oximes of α, β-unsaturated acids.     

Crystal Structures of β-Cyclodextrin Complexes with Formic Acid and Acetic Acid

β-Cyclodextrin (β–CD)-formic acid (1) andβ-CD–acetic acid (2) inclusion complexes crystallizeas β-CD...0.3HCOOH...7.7H₂O andβ-CD...0.4CH₃COOH...7.7H₂O in themonoclinic space group P2₁ with comparable unit cell constants.Anisotropic refinement of atomic parameters against X-ray diffractiondata with F_o ² > 2σ (F_o ²) (986/8563 and 991/8358)converged at R-factors of 0.051 and 0.054 for 1 and 2,respectively. In both complexes, the β-CD molecularconformation, hydration pattern and crystal packing are similar,but the inclusion geometries of the guest molecules are different.The β-CD macrocycles adopt a ``round'' conformationstabilized by intramolecular, interglucose O3(n)...O2(n + 1)hydrogen bonds and their O6–H groups are systematically hydratedby water molecules. In the asymmetric unit, each complex contains oneβ-CD, 0.3 formic acid (or 0.4 acetic acid), and 7.7 water moleculesthat are distributed over 9 positions. Water sites located in theβ-CD cavity hydrogen bond to the guest molecule. In thecrystal lattice, β-CD molecules are packed in a typical ``herringbone'' fashion. In 1, the formic acid (occupancy 0.3) is entirely included in the β-CD cavity such that its C atom is shifted from the O4-plane center to the β-CD O6-side by 2.90 Å and C=O, C–-O bonds point to this side. In 2, the acetic acid (occupancy 0.4) is completely embedded in the β-CD cavity, in which the carboxylic C atom is displaced from the O4-plane centerto the β-CD O6-side by 0.87 Å; the C=O bond directsto the β-CD O6-side and makes an angle of 15°to the β-CD molecular axis. Furthermore, bothdimethyl-β-CD-acetic acid and β-CD-acetic acidcomplexes form a cage structure, showing that the small guestsenclosed entirely in the cavity either in β-CD or indimethyl-β-CD do not affect the packing of the host macrocycles.     

The Interaction of β-Cyclodextrin with Benzoic Acid

The interaction of β-cyclodextrin with benzoic acid was studied by UV and IR spectroscopy, X-ray diffraction, and thermogravimetry. The introduction of the benzoic acid molecule into the internal hydrophobic β-cyclodextrin cavity and additional stabilization by weak H-bonds caused the formation of 1: 1 axial inclusion complexes of the host—guest type. The degree of crystallinity of the inclusion complex decreased compared with the initial compounds, whereas its thermal stability increased.     

Acid–Base Behavior in Supercritical Water: β-Naphthoic Acid–Ammonia Equilibrium

Equilibrium constants for the reaction of -naphthoic acid and ammonia, K _BHA, were measured with UV-vis spectroscopy in water from 25°C to 400°C. At high density K _BHA decreases with temperature, the normal behavior for an exothermic reaction of a stronger acid and base to a weaker acid and base. At low density, the reaction becomes endothermic as the solvation of the ionic products becomes weaker. These data were combined with literature results for the dissociation of water and ammonia to determine equilibrium constants for the dissociation of -naphthoic acid and the reaction of -naphthoic acid and OH^- Whereas the density (and dielectric constant) of water have only a modest effect on the isocoulombic reaction of -naphthoic acid and OH^-, they have a large effect on all of the other reactions which are ionogenic.     

Dielectric Relaxation of the β-Cyclodextrin Complexes with Tridecanoic Acid and 1,13-Tridecanedioic Acid

The frequency and temperature dependence of the real (') and imaginary (') parts of the dielectric permittivity of the polycrystalline complex-cyclodextrin-tridecanoic acid in two hydration forms (with 16.2 and 10.7 water molecules) and -cyclodextrin-1,13-tridecanedioic acid with 16.4 and 10.5 water molecules have been investigated, in the frequency range 0.1–100 kHz and temperature range 120–310 K. The dielectric behavior is described well by Debye-type relaxation dispersion. All systems except for the complex of partially dehydrated monocarboxylic acid, exhibit an additional -dispersion, at low frequencies (f < 1000 Hz). Only one-step was found in the ' vs. Tplots of both complexes in the two hydration forms, a fact indicating that the watermolecules cannot be divided into strongly bound and easily movable molecules. The'vs. T plots, at a fixed frequency (200 Hz), show the characteristic peakattributed to a transition between ordered and disordered -CD hydroxyl groupsand water molecules. The transition temperature was 202.7 K for all systems examinedexcept for the complex -CD-tridecanoic acid.16.2 H₂O (214.5 K). This means that the order to disorder transformation process was unaffected by the dehydration process in the case of the dicarboxylic acid complex, whereas in the case of the monocarboxylic acid, it was unexpectedly facilitated. The relaxation time varies with temperature, in a like curve (in the range 8–14 s), with maximum values located at the corresponding order-disorder transition temperatures. The activation energies of the fully hydrated complexes have absolute values of 5 kJ/mol in the range 1.98–3.82 K_{BT transition} which are higher than the corresponding values of :2 kJ/mol of the dehydrated complexes. A thermal hysteresis observed in all complexes is a result of the order-disorder transformation.     

Condensation of p-Benzoquinone with Anilides of β-Aminocrotonic Acid

Benzofuranone derivatives have been synthesized by the condensation of p-benzoquinone with anilides of -aminocrotonic acids under the conditions of the Nenitzescu reaction.     

Solid-Phase Synthesis of Acrylamide Using Polymer-Supported β-Selenopropionic Acid

A novel polystyrene-supported β-selenopropionic acid has been developed and applied to facile synthesis of acrylamides.     

Coulometric Titration of Thiocyanate,Mercaptoacetic Acid,and β-Mercaptopropionic Acid with Electrogenerated Hypobromite

Abstract

Several sulfur containing ligands have been determined by coulometric titration using biamperometric end point detection. Satisfactory results were obtained for the direct determination of thiocyanate, mercaptoacetic acid and β-mercaptopropionic acid. Silver has been determined by an indirect method involving the determination of excess precipitant.     

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.     

Inclusion Behavior of Dimer β-CyclodextrinBridged with Aspartic Acid Derivative

The capped cyclodextrins (CDs) are very useful macromolecular hosts in supramolecular chemistry. Previously, we demonstrated that the dimer cyclodextrin bridged with 1,2-diaminoethane causes significant enhancement of affinity to a small organic guest molecule1. A variety of interesting peptides have been developed as artificial enzymes. Here our designed peptide, Adm-Trp-Arg-Arg-NH2, named ATA was synthesized by the usual solid-phase Fmoc strategy2 with trityl resin in Shimadzu-PSSM8 p…     

Dehydration of β-Hydroxy-α-amino Acid Derivatives With Phenyltriflimide

Conversion of N-protected β-hydroxy-α-amino esters to corresponding didehydroamino esters has been achieved using phenyltriflimide/triethylamine as a mild dehydrating agent. The selective formation of didehydroalanine derivatives from dipeptides containing, beside a serine residue, another β-hydroxy-α-amino acid, is also described.     

Friedel-Crafts Polymers. 6. Friedel-Crafts Polycondensation of p-Xylylerte Dibromide with Salicylic Acid and β-Resorcyiic Acid

Polymers were prepared by condensing p-xylylene dibromide separately with salicylic acid and β-resorcylic acid in the presence of anhydrous ferric chloride in dioxane. The polymer samples_were characterized by elemental analysis, by IR spectral study, by M determined by vapor pressure osmometry, by nonaqueous conducto-metric titration in pyridine, by TGA in air, and by viscosity measurements of polymer solutions in DMF. Polymeric metal chelates of Cu²⁺, Co²⁺, Zn²⁺, Ni²⁺, and Fe³⁺ with polymer samples were prepared and characterized by elemental analysis, by IR spectral study, and by TGA in air. The chelation ion-exchange properties of the polymer samples were studied by employing the batch equilibration method.     

Synthesis of 1,3-Dioxolane Derivatives from β-Chlorolactic Acid and Ketones

2-Ethyl-2-methyl-5-methylene-1,3-dioxolan-4-one and 5-methylene-2,2-pentamethylene-1,3-dioxolan-4-one were synthesized by reaction of -chlorolactic acid with methyl ethyl ketone and cyclohexanone, respectively, followed by dehydrochlorination of intermediate 5-chloromethyl derivatives.     

Versatile Post-synthetic Modifications of Helical β-Peptide Foldamers Derived from a Thioether-Containing Cyclic β-Amino Acid

We introduce a novel cyclic β-amino acid, trans-(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of β-peptide hexamers containing ATTC using various techniques, including X-ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC-containing foldamers can adopt 12-helical conformations similar to their isosteres and offer the possibility of fine-tuning their properties via post-synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post-synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic β-amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond.     

One-Pot Synthesis of 2,4-Disubstituted Thiazoline from β-Azido Disulfide and Carboxylic Acid

A concise and efficient one-pot four-step synthesis of 2,4-disubstituted thiazoline via a cascade disulfide bond cleavage/thiocarbonylation/Staudinger reduction/aza-Wittig reaction is established. Treatment of various carboxylic acids with β-azido disulfides under this one-pot procedure obtained the desired thiazolines in good to excellent isolated yields.     

Improving the Selectivity of the Phosphoric Acid β-Elimination on a Biotinylated Phosphopeptide

This study aims at improving the MALDI-TOF detection of a phosphorylated peptide containing a cysteine residue by ??-elimination of H₃PO₄ hardly enriched by classical methods. The experimental conditions were optimized on this phosphopeptide (biot-pAdd) and its nonphosphorylated counterpart (biot-Add). The major side-reactions were H₂S elimination on the cysteine residues and H₂O elimination on the non phosphorylated serine residue of biot-Add. The former dilutes the MALDI-TOF signal for the desired species. The latter gives a product similar to what is obtained by H₃PO₄ elimination and should prompt to caution when working with a mixture between phosphorylated and non phosphorylated peptides. Modifications on the solvent, the reaction temperature and time, the nature, and concentration of the base were made. Major improvement of the selectivity of the reaction was observed in 30?% ACN, at room temperature for 4?h. However, these optimizations are specific to these sequences and should be performed anew for different peptides. The selectivity of the reaction towards H₃PO₄ elimination is improved, but the persistence of side-reactions renders a previous sample fractionation necessary. In these optimized conditions, the ionization enhancement is 3-fold and the detection limits for biot-pAdd are similar to biot-Add (100?fmol).     

Interaction of Amino Acid and Dipeptide β-Naphthylamide Derivatives with Hyaluronic Acid and Human Serum Albumin Studied by Capillary Electrophoresis Frontal Analysis

Interactions of drug candidates with the biomacromolecules of the synovial fluid affect drug targeting to the articular cartilage as well as clearance from the synovial space upon intra-articular administration. Hyaluronic acid (HA) and human serum albumin (HSA) are two main components existing in the synovial fluid. To this end, we investigated the affinity of seven cationic amino acid and dipeptide β-naphthylamide derivatives towards HA and HSA in order to shed light on possible relationships between physicochemical properties, in particular charge state, and biomacromolecular interactions to increase the joint residence time. Capillary electrophoresis frontal analysis was used for characterization of the binding of the derivatives to hyaluronic acid and HSA at 25 °C in acetate buffer (pH 4.65) and phosphate buffer (pH 7.40), respectively. Linear binding isotherms were observed for the ligand–hyaluronic acid interactions and the obtained binding constants ranged from 43 to 133 M^?1. The average fraction of bound ligand towards hyaluronic acid increased with increasing the net charge of the ligands but was less than 67 % for all investigated ligands. The obtained binding constants of the ligands with HSA varied in the range of 10³–10⁶ M^?1. The interactions of low-molecular weight derivatives with hyaluronic acid were highly dependent on the ligand charge state. This trend was not observed for the interactions with HSA. The obtained affinity data may provide useful information in the design of cartilage adhesive prodrugs with extended residence time in the synovial cavity.     

Enantioselective Synthesis of β-Amino Acid Derivatives Enabled by Ligand-Controlled Reversal of Hydrocupration Regiochemistry

A Cu-catalyzed enantioselective hydroamination of α,β-unsaturated carbonyl compounds for the synthesis of β-amino acid derivatives was achieved through ligand-controlled reversal of the hydrocupration regioselectivity. While the hydrocupration of α,β-unsaturated carbonyl compounds to form α-cuprated species has been extensively investigated, we report herein that, in the presence of an appropriate ancillary chiral ligand, the opposite regiochemistry can be observed for cinnamic acid derivatives, leading to the delivery of the copper to the β-position. This copper can react with an electrophilic aminating reagent, 1,2-benzisoxazole, to provide enantioenriched β-amino acid derivatives, which are important building blocks for the synthesis of natural products and bioactive small molecules.     

Study on the Structure of Supramolecular Inclusion Complex of β-Cyclodextrin with Retinoic Acid

The importance of Vitamin A for human health has been stressed in resent studies1, meanwhile its derivative so-called retinoic acid (RA) has been widely used as pharmaceutical to treat several types of skin disease and cancer2,3. However the application of retinoic acid is restrained for its poor water solubility, unstability and side effect on the human body.Cyclodextrins (CDs) are macrocyclic oligosaccharides built up from 6, 7, or 8 glucopyranose units called (, (, and (-CD, respectively…