Β-amino Acid Esters Research Articles

A New Class of Biodegradable Thermosensitive Polymers. 2. Hydrolytic Properties and Salt Effect on the Lower Critical Solution Temperature of Poly(organophosphazenes) with Methoxypoly(ethylene glycol) and Amino Acid Esters as Side Groups

The hydrolytic properties of the novel biodegradable thermosensitive poly(organophosphazenes) with methoxypoly(ethylene glycol) (MPEG) and amino acid esters as side groups have been studied by means of gel permeation chromatography and 31P and 1H NMR spectroscopy and by identification of the hydrolysis products. The polymers substituted with α-amino acid esters were hydrolyzed faster than that with β-amino acid ester. The higher content of the amino acid ester in the polymer backbone caused enhanced hydrolysis. The rate of the polymer degradation decreased in the order of methyl > ethyl > benzyl esters. The polymer hydrolysis occurred more rapidly in both acidic and basic buffer solutions than in the neutral solution. The 31P NMR spectra of the polymers with high content of glycine ethyl ester showed that the polyphosphazene backbone underwent fragmentation mostly to small molecules after incubation in the buffer solution of pH 10 for 26 days. Phosphates and ammonia were formed as hydrolysis products in most cases. The hydrolytic behaviors of the present thermosensitive polyphosphazenes are consistent with the conventional acid-catalyzed degradation mechanism, and a detailed pathway to their hydrolytic degradation is proposed. The salt and pH effects on the thermosensitivity of the polymers were also examined by measuring their lower critical solution temperature (LCST) in aqueous solutions containing various inorganic and organic salts. When various inorganic salts were added to aqueous solutions of the polymers, their salting-in and salting-out effects were found to be mainly dependent on the anions of the salts. On the other hand, in the case of tetraalkylammonium halides which are organic salts, cations seem to play an important role: the salting-in effect is stronger with increasing alkyl chain of the ammonium salt. The aqueous solutions of the polymers showed higher LCST in the acidic solution than in the neutral and basic buffer solutions.

Enantioselective synthesis of β-amino acids. Part 10: Preparation of novel α,α- and β,β-disubstituted β-amino acids from ( S)-asparagine

Perhydropyrimidinone ( S)- 1 is alkylated with very high diastereoselectivity to give trans products (2 S,5 R)- 3, (2 S,5 R)– 4 and (2 S,5 R)- 5. Dialkylation of ( S)- 1 also proceeds with complete stereoselectivity to afford adducts (2 S,5 R)- 6, (2 S,5 S)- 6, (2 S,5 R)- 7 and (2 S,5 S)- 7. Hydrolysis (6N HCl, 100°C) of monoalkylated derivative (2 S,5 R)- 3 gives enantiopure α-substituted β-amino acid ( R)- 8. Hydrolysis of dialkylated adducts 6 and 7 affords enantiopure α,α-disubstituted β-amino acids ( R)- or ( S)- 9 and ( R)- or ( S)- 10. Related iminoester (2 S,6 S)- 2 is alkylated with complete diastereoselectivity to give products (2 S,6 S)- 11– 13 whose hydrolysis under relatively mild conditions (2N CF 3CO 2H, CH 3OH, 100°C) affords enantiopure N-benzoylated β,β-disubstituted β-amino acid esters ( S)- 14– 16, with intact double bonds in the olefinic substituents.

One-Pot Process for the Preparation of a β-Alkynyl β-Amino Acid Ester

The large-scale preparation of the β-alkynyl β-amino acid ester (±)-1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate (A) is discussed. It was discovered that addition of a catalytic amount of lithium bis(trimethylsilyl)amide (LHMDS) to a mixture of tert-butyl acetate and N,3-bis(trimethylsilyl)-2-propyn-1-imine (B) initiated a self-perpetuating reaction and gave high yields of the β-amino ester A upon quench. This one-pot procedure eliminated the need to prepare the unstable lithium tert-butyl acetate in a separate reactor and enabled the reaction to be scaled up and run at a more acceptable process temperature (−20 °C) compared to the analogous two-pot reaction (−45 °C). Addition of 3-(trimethylsilyl)-2-propynal to LHMDS in THF at −20 °C followed by chlorotrimethylsilane formed the imine B in situ. tert-Butyl acetate (6 equiv) was added followed by a substoichiometric quantity (0.15−0.20 equiv) of LHMDS. After quenching with aqueous ammonium chloride the product A was obtained in a yield averaging 70%.

The application of microwave irradiation to the Michael synthesis of esters of β-amino acids

Microwave irradiation accelerates the Michael 1,4-addition of primary and cyclic secondary amines to esters of α,β-unsaturated α-unsubstituted carboxylic acids.

Approach to highly enantiopure β-amino acid esters by using lipase catalysis in organic media

Ethyl esters of ten alicyclic β-aminocarboxylic acids were resolved by lipase catalysis in organic solvents. The resolution was based on acylation of the amino group at the R -stereogenic centre with various 2,2,2-trifluoroethyl esters. An increase in the hydrophobic nature of the acyl donor enhanced the enantioselectivity and reactivity in the case of lipase SP 526 from Candida antarctica , while the opposite effect was observed with lipase PS from Pseudomonas cepacia . An unexceptional enantioselectivity enhancement was observed when 2,2,2-trifluoroethyl chloroacetate was used in the case of lipase PS catalysis. Ethyl esters of ten alicyclic β-aminocarboxylic acids were resolved by lipase catalysis in organic solvents.

Hydrogenation of 1-benzyl-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-aziridine-2-carboxylic acid ethyl ester

Hydrogenation of 1-benzyl-aziridine-2-carboxylic acid ethyl ester 1 yielded the enantiomerically pure 1H-aziridine 2 or the β-amino acid ester 3 as main products depending on the reaction time. The Z-protected derivatives of 2 and 3 were transformed into the γ-lactones 4 and 5, respectively.

First synthesis of optically pure α-amino amine as asymmetric amino transfer reagent and its use in asymmetric Mannich reaction

An optically pure α-amino amine was first synthesized from L-lysine utilizing anodic oxidation as a key step, and its usefulness was exemplified by the asymmetric Mannich reaction to give optically active β-amino acid esters.

Biocatalytic asymmetric synthesis of β-aminoacid esters: improved chiral recognition in the presence of β-cyclodextrin

Biocatalytic asymmetric synthesis of β-aminoacid esters: improved chiral recognition in the presence of β-cyclodextrin

Highly enantioselective and diastereoselective synthesis of β-amino acid esters and β-lactams from achiral esters and imines

The reaction of S-tert-butyl thiopropionate with a number of N-benzyl or N-allyl aldimines ( 4) as promoted by the chiral diazaborolidine 1 and triethylamine afforded the β-amino acid esters 5 with high diastereoselectivity and enantioselectivity, providing a simple route to chiral β-lactams 6.

Highly enantioselective routes to darzens and acetate aldol products from achiral aldehydes and t-butyl bromoacetate

New methodology is described for the enantioselective coupling of t-butyl bromoacetate with aldehydes to give anti-α-bromo β-hydroxy esters ( 1), useful precursors of chiral glycidic esters ( 2), acetate aldols ( 3), β-amino acid esters ( 4) and α-amino acid esters ( 5).

A water-soluble tweezers-like metalloreceptor: binding and selective catalytic properties

The amphiphilic molecule 1 binds lipophilic substrates below its critical aggregate concentration and, in a complex with two CuII ions, is a catalyst for the hydrolytic cleavage of activated esters of β-amino acids and an inhibitor of that of α-amino acids.

The Directed Cleavage of Substituted 1-Phenylethylamines: A Novel Route to Enantiomerically Pure β-Amino Acid Esters and β-Lactams

An efficient novel access to enantiomerically pure ß-amino acid esters and ß-lactams (e.g., methyl (3S,4S)-1-(tert-butyldimethylsilyl-4-methyl-2-oxoazetidine-3-carboxylate) from optically active 1-arylethylamines is described. Regiospecific cleavage is performed by Birch reduction and subsequent ozonolysis.

Stereoselective synthesis of cis-4-(substituted) monobactams from ethyl acetoacetate

The stereoselective synthesis of cis-3-amino-4-methyl-2-oxoazetidine-1-sulphonic acid (25) from ethyl acetoacetate is described. Nitrosation of this compound and reduction of the resulting oxime gave the corresponding amine, which after treatment with different acyl halides, yielded the acylamino derivatives (6)–(8). Condensation with p-anisidine gave the enamines (12)–(14), which were then reduced to the β-amino acid esters (15)–(17). Stereoselective cyclization with Grignard reagents as base, and appropriate deprotection and sulphonation of the resulting β-lactams (18)–(20), led to the title compounds.

A novel oxidative ring-opening reaction of isoxazolidines: syntheses of β-amino ketones and β-amino acid esters from secondary amines

A novel oxidative ring-opening reaction of isoxazolidines upon treatment with an electrophile and subsequently with a basegives β-amino ketones and β-amino acid esters highly efficiently.

Stereochemical studies 87 saturated heterdcycles 82 : Synthesis and steric structure of steredisomeric [formula omitted]-substituted tetrahydro-1,3-oxazines fused with norbornane or norbornene

diendo - and diexo -2-Methylamino and 2-benzylamino-3-hydroxymethylbicyclo [2.2.1]heptanes and the corresponding bicycio [2.2.1] heptenes ( 5a - d , 7a - d ) were synthesized from β-amino acid esters containing the norbornane or norbornene skeleton ( 3a - d ). The aminoalcohols were converted to 5,8- methano -3,1-benzoxazines by reaction with formaldehyde. As established by 1H and 13C NMR spectroscopy, the predominant conformation is endo - boat ( B ) for the diexo , and exo - boat ( E ) for the diendo derivatives.

Poly-β-Amino Acids. I. The Preparation of Phenyl Substituted β-Amino Acid Polymers

Abstract α-Phenyl-, β-phenyl-, and α,β-diphenyl-β-aminopropionic acid were synthesized. Their polymers were obtained in good yields when the p-nitrophenyl esters of β-amino acids were polymerized at 60°C. The ethyl esters gave low-molecular-weight polymers in poor yields at 150°C in vacuo. By the thermal polycondensation of β-amino acids themselves at 250°C, polymers were not obtained, but the corresponding cinnamic acid derivatives were obtained by the intramolecular β-elimination reaction. Poly(α-phenyl-β-amino acid), and poly(β-phenyl-β-amino acid) were soluble in trifluoroacetic acid, and chloroform containing a small amount of dichloroacetic acid. On the other hand, poly(α,β-diphenyl-β-amino acid) was soluble only in cone, sulfuric acid, while it was insoluble in usual organic solvents. The DP of poly(β-phenyl-β-amino acid) was about 18. None of the polymers showed any melting point below 300°C.

Studies on application of amino acid as medicinal agent. I. Syntheses of amino-tert-alcohol derivatives.

In order to find non-narcotic analgesics, 54 compounds of amino-tert-alcohol, in which a variety of substituent groups were involved at the carbon atom in 1-position and at the amino group, were synthesized by reacting various α-and β-amino acid esters with Grignard reagents. These amino acid esters were readily reacted with alkyl Grignard reagents to give the expected compounds. However, when bulky aromatic Grignard reagents were submitted to react, the reactions were found to stop at the stage of intermediate formation of the corresponding ketones.

The curtius reaction in the?-amino acid series

1. A general method has been developed for the preparation in good yield on N-benzoylated imidazolidone derivatives by the Curtius reaction, which is applied to esters of N-benzoylated β-amino acids. 2. The reaction has been carried out with N-benzoyl-β-phenyl-β-alanine, N-benzoyl-β-(m-nitrophenyl)-β-alanine, and N-benzoyl-β-piperonyl-β-alanine. 3. It has been found that reaction of excess of hydrazine hydrate with N-benzoyl-β-(m-nitrophenyl)-β-alanine yields the hydrazide of β-(m-aminoplienyl)-N-benzoryl-β-alaniiie, i.e., reaction is accompanied by reduction of the Witro group.