Β-alanine Ester Research Articles

Functionalization of the position 5 of thiopyran fragment of 4-(diethoxyphosphoryl)-4,7-dihydro-5 Н-thiopyrano[3,4-b]furan

Alkaline hydrolysis of ethyl 4-(diethoxyphosphoryl)-4,7-dihydro-5 Н -thiopyrano[3,4- b ]furan-5-carboxylate proceeded selectively at the ester group. The acid obtained formed the corresponding acid chloride when treated with thionyl chloride. The acid chloride was used for acylation of glycine, α- and β-alanine esters. Under the conditions of phase transfer catalysis this acid chloride formed acyl azide which under mild conditions undergoes rearrangement to isocyanate. The latter reacted with primary amines to give ureas, and with the amino acid esters in forms ureidoesters. Reducing of acid chloride with sodium borohydride led to the corresponding alcohol. It was converted to chloride which in the reactions with sodium azide and iodide gives usual substitution products. When treated with potassium thiocyanate it formed thiocyanate. Iodide in the reaction with triethyl phosphite gave the corresponding phosphonate. Oxidation of alcohols with Collins reagent and acetic acid-DMSO system was studied.

The Role of Formamidine Groups in Dextran Based Nonviral Vectors for Gene Delivery on Their Physicochemical and Biological Characteristics.

Dextran-formamidine esters (dextran-N-[(dimethylamino)methylene]-β-alanine ester) with different degrees of substitution (0.45-0.92) are synthesized in an one-pot reaction. Dextran (Mw 60 000g mol-1 ) is allowed to react with unprotected beta-alanine and iminium chloride and investigated regarding the potential as gene delivery system for the transfer of plasmid DNA. With degrees of substitution ≥ 0.63 improved DNA binding with formation of enzymatically stable complexes of about 130-160nm with negative surface charges are obtained. These physicochemical characteristics correlated with increasing transfection rates in CHO-K1 cells determined by a luciferase reporter gene assay in dependency of the number of formamidine residues, N/P ratios and amount of DNA. The role of the number of formamidine groups is also highlighted by in vitro cyto- and hemotoxicity tests under the chosen conditions. These results indicate that dextran-formamidine esters are a very promising material for the safe and efficient gene delivery.

Amino Acid-Substituted Dextran-Based Non-Viral Vectors for Gene Delivery.

To form bio-inspired non-viral vectors for DNA delivery, the polysaccharide dextran is allowed to react with Boc-amino protected amino acids glycine, β-alanine, and L-lysine activated with 1,1'-carbonyldiimidazole and subsequent dextran ester deprotection. A library of such dextran esters is made available to investigate the relationship between polymer structure, complex formation, stability, toxicity, and transfection. Only dextran esters of β-alanine and L-lysine are able to efficiently interact with DNA as shown by dye exclusion assays, to form nanosized complexes (70-110 nm) with positive zeta potential. With increasing substitution degree and complex charge ratios, the L-lysine esters accomplish more effective binding and protection of DNA against enzymatic degradation than β-alanine esters. However, luciferase reporter gene assays reveal higher transfection for β-alanine than for L-lysine esters due to a more effective DNA release and better suited buffing area of the amino groups triggering the endosomal release. Conclusively, β-alanine-substituted dextran derivatives may serve as promising non-viral vectors.

Novel dextran derivatives with unconventional structure formed in an efficient one-pot reaction

An efficient one-pot synthesis of new dextran derivatives is described. The functional groups of β-alanine, i.e., the carboxyl- and amine group, are converted independently in one-step by iminium chloride to form products with a single substituent. The dextran N-[(dimethylamino)methylene]-β-alanine ester is formed selectively. The structure of the resulting polymers is unambiguously determined by means of NMR- and FTIR-spectroscopy and elemental analysis.

Enzyme-Catalyzed Polymerization of β-alanine Esters, A Sustainable Route Towards the Formation of Poly-β-alanine

The synthesis of poly-β-alanine by a lipase catalyzed polycondensation reaction between β-alanine esters is reported. The effect of different solvents, reaction temperatures and substrate/enzyme concentrations on polymer yield and degree of polymerization (DP) was determined. Also the effect of methyl substituents at the α and β position of β-alanine was studied. Cross-Linked Enzyme Aggregates (CLEA) of Candida antarctica lipase B converted β-alanine esters into polymers in high yield (up to 90%) and with high (DP) (up to 53 units). Optimum results were obtained when methyl esters are used in methyl tert-butyl ether (MTBE) as the solvent, at 50°C for 16 h. Keywords: Biobased, biocatalysis, CLEA, enzymatic catalysis, lipases, Novozyme 435, nylon 3, polyamides.

N,3,4-Trisubstituted pyrrolidines by electron transfer-induced oxidative cyclizations of N-allylic β-amino ester enolates

Oxidative radical cyclizations starting from easily accessible N-allylic β-alanine esters are reported. Deprotonation generates the corresponding enolates, which are transformed efficiently into α-ester radicals by single electron transfer mediated by ferrocenium hexafluorophosphate. The stereochemistry of the radical 5- exo cyclization can be switched by the configuration of the enolate precursor. First examples of asymmetric oxidative radical cyclizations using N-(1-phenylethyl)-substituted β-amino esters are reported. Only two of the four possible diastereomers are formed from the ( E)-enolate with high cis-selectivity. From ( Z)-enolates, an additional diastereomer is formed, which is likely to be formed only under chelation control.

Synthesis of new organothiophosphorus insectoacaricides containingN-acylated amino acid fragments

Methods for the synthesis ofO-alkylS-(N-acyl-N-alkoxycarbonylalkyl)aminomethyl (methyl)thio- and -dithiophosphonates based on the reaction between alkaline-metal salts ofO-alkyl (methyl)thio- and -dithiophosphonates and N-alkoxycarbonyl-N-chloromethylglycine or -β-alanine esters and by treatment ofO-alkyl (methyl)dithiophosphonoates andN-acylated amino acids or their esters with paraform in the presence of HCl were developed. The compounds obtained exhibit high insectoacaricide activity and selectivity.

MICHAEL-TYPE ADDITION OF DIETHYL PHOSPHORAMIDATE TO α,β-UNSATURATED ESTERS

Abstract Michacl-type addition of diethyl phosphoramidate to α,β-unsaturated esters occurs when the reactants are refluxed in toluene or xylene with an excess of potassium carbonate in the presence of tetrabutyl-ammonium bromide (TBABr). Dephosphorylation of methyl and ethyl acrylate adducts leads to the respective β-alanine esters.

ChemInform Abstract: STUDIES OF UNUSUAL AMINO ACIDS AND THEIR PEPTIDES. VI. THE SYNTHESES AND THE OPTICAL RESOLUTIONS OF β‐METHYLPHENYLALANINE AND ITS DIPEPTIDE PRESENT IN BOTTROMYCIN

AbstractDurch Kondensation von α‐Methyl‐benzylbromid (aus Styrol und HBr) mit Acetaminomalonsäurediäthylester wird das Produkt (I) (73% Ausbeute) erhalten, das nach Hydrolyse, Decarboxylierung und Desacetylierung die Aminosäure (II) lieferte.

Studies of Unusual Amino Acids and Their Peptides. VI. The Syntheses and the Optical Resolutions of β-Methylphenylalanine and Its Dipeptide Present in Bottromycin

Abstract β-Methyl-phenylalanine was prepared by the condensation of α-methylbenzyl bromide with acetaminomalonate, followed by the hydrolysis and decarboxylation of the condensate. The decarboxylation occurred diastereoselectively to some extent. The erythro and the threo isomers could be separated by the fractional crystallization of their benzoyl derivatives, and differentiated by means of their NMR spectra. The optical resolution of the respective isomers was attained by treating the benzyloxycarbonyl derivatives with qunine or quinidine; thus, the four isomers could be obtained in a pure state. A dipeptide present in the C-terminal of bottromycin was synthesized by coupling N-protected erythro-l-β-methyl-phenylalanine with either l-β-(2-thiazolyl)-β-alanine ester or, more conveniently, with the Dl-compound, and by separating thereafter.

Room-temperature polycondensation of beta-amino acid derivatives. I. Polyamide from amino alcohols and acrylates.

Acrylates, such as ethyl acrylate, add with amino alcohol to form N-(hydroxyalkyl) β-alanine ester and room-temperature polycondensation follows, forming polyamide in the presence of a basic catalysts, such as alkali metal alkoxide. The reaction medium has an influence on the course of the polycondensation; that is, N-(hydroxyalkyl) polyamide is formed in methanol solution and polyamide ether in other solvents, such as tetrahydrofuran. These two courses of the room-temperature polycondensation have been studied, and the reaction mechanism is discussed in this paper.