Α-hydroxy Acid Esters Research Articles

Facile synthesis of new N-(aminocycloalkylene)amino acid compounds using chiral triflate esters with N-Boc-aminopyrrolidines and N-Boc-aminopiperidines.

In this study, we prepared a series of new N-(aminocycloalkylene)amino acid derivatives for use in chiral building blocks. The method was based on the conversion of enantiopure α-hydroxy acid esters into the corresponding chiral triflate esters, which were displaced by a nucleophilic substitution SN2 reaction with aminopyrrolidine and aminopiperidine derivatives, and the inversion of the configuration to give methyl 2-[(Boc-amino)cycloamin-1-yl]alkanoates with good yield and high enantiomeric and diastereomeric purity. Synthesized 2-[(Boc-amino)piperidin-1-yl]propanoates combined with ethyl l-phenylalaninate gave new chiral N-Boc- and N-nosyl-dipeptides containing a piperidine moiety. The structures were elucidated by 1H-, 13C-, and 15N-NMR spectroscopy, high-resolution mass spectrometry, and X-ray crystallography analyses.

Use of lithium aryloxides as promoters for preparation of α-hydroxy acid esters.

In this work, a hexanuclear lithium compound, [Li6(MesalO)6] (1), supported by a chelating ligand, namely methyl salicylato (MesalOH), was used as a precursor for preparation of the monomeric lithium aryloxides [Li(MesalO)(MesalOH)] (2) and [Li(MesalO)(MeOH)2] (3) via reactions with MesalOH or MeOH. These aryloxides were characterized by single-crystal X-ray diffraction, and spectroscopic and other analytical methods. The diffusion-ordered 1H NMR measurements revealed the retention of solid-state structures of 1 and 2 in THF-d8 solution. Experimental data obtained for 3 showed its decomposition into compound 1 and free MeOH. Compound 1 generated from 3 was also used as a catalyst for the alcoholysis of l-lactide (l-LA) and glycolide (GA) for the preparation of α-hydroxy acid esters. We established that during methanolysis in the presence of 1, l-LA was selectively transformed into methyl (S,S)-O-lactyllactate (MeL2), and GA was converted to methyl glycolate (MeG1) and oligoglycolate esters MeGn (n = 2, 3, and 4).

Copper-catalyzed intramolecular redox reaction: Asymmetric synthesis of chiral 2-(1H-pyrrol-1-yl)-mandelic acid esters

An efficient approach to chiral α-hydroxy acid esters by Lewis acid-mediated asymmetric [1,5]-hydride shift and isomerization of 2-(3-pyrroline-1-yl)arylketone acid ester has been achieved in up to 96% yield and 94% ee. This protocol would be applied in the synthesis of chiral α-hydroxy acid derivatives with simplicity and high enantioselectivity.

Synthesis of trifluoromethylated α-hydroxy acids and their derivatives based on alkyl trifluoropyruvates

The reactions of trifluoropyruvates with nitromethane and arylmagnesium bromides leading to trifluoromethyl-containing α-hydroxy acid esters were studied and various derivatives of the acids were obtained.

The assignment of the configuration for α-hydroxy acid esters using a CEC strategy.

A simple and efficient (1)H NMR method for determining the absolute configuration of chiral α-hydroxy acid esters using a competing enantioselective conversion (CEC) strategy was developed. The α-hydroxy acid esters were acylated in the presence of Feng's chiral N,N'-dioxide-scandium(iii) complex, and the faster reaction was identified when one enantiomer of the chiral α-hydroxy acid ester was treated with both enantiomers of the ligand by NMR analysis of the reaction mixture without further purification. A mnemonic is presented to aid the assignment of the absolute configuration of the substrates.

Confinement Effects in Lewis Acid-Catalyzed Sugar Conversion: Steering Toward Functional Polyester Building Blocks

We report the use of solid Lewis acid catalysts for the conversion of tetrose sugars to four-carbon α-hydroxy acid esters (C4-AHA), which are useful as functional polyester building blocks. Sn-β was by far the most active and selective catalyst, yielding up to 80% methyl vinyl glycolate (MVG), methyl-4-methoxy-2-hydroxybutanoate (MMHB), and α-hydroxy-γ-butyrolactone (HBL) combined at 95% conversion. A very high turnover frequency (TOF) of 330 molC4-AHA molSn h–1 was attained using Sn-β, a more than 6-fold increase compared with homogeneous SnCl4·5H2O. It is shown that, using different Sn-based catalysts with various pore sizes, the product distribution is strongly dependent on the size of the catalyst pores. Catalysts containing mainly mesopores, such as Sn-MCM-41 or Sn-SBA-15, prefer the production of the more bulky MMHB, whereas microporous catalysts such as Sn-β or Sn-MFI favor the production of MVG. This effect can be further enhanced by increasing the reaction temperature. At 363 K, only 20% MVG is a...

Characterization Studies of Aluminum Alloy Substrate Surfaces Treated By Oxyanion Esters of Α-Hydroxy Acids and Their Salts

Characterization Studies of Aluminum Alloy Substrate Surfaces Treated By Oxyanion Esters of Α-Hydroxy Acids and Their Salts

Metal-Free Tandem Friedel–Crafts/Lactonization Reaction to Benzofuranones Bearing a Quaternary Center at C3 Position

A metal-free tandem Friedel-Crafts/lactonization reaction to 3,3-diaryl or 3-alkyl-3-aryl benzofuranones catalyzed by HClO(4) was reported. A variety of tertiary α-hydroxy acid esters could readily react with substituted phenols to afford the desired products in rich diversity. The synthetic utility of the products was demonstrated by the synthesis of polycyclic compounds. (1)H NMR studies supported that this tandem reaction proceeded via tandem Friedel-Crafts/lactonization sequence.

Lipase activity of Lecitase® Ultra: characterization and applications in enantioselective reactions

The general properties of Lecitase® Ultra, a phospholipase manufactured and marketed by Novozymes, Denmark, have been studied after purification by ultrafiltration. The enzyme has a molecular mass of 35 KD, pH-optimum of 8.5, and appears to possess a single active site which exhibits both the lipase and phospholipase activities that increase in the presence of Ca 2+ and Mg 2+ ions. The enzyme is inhibited by heavy metal ions and surfactants, and does not accept p-nitrophenyl acetate and glycerol triacetate. Substrates, such as glycerol tributyrate and p-nitrophenyl palmitate, esters of N-acetyl-α-amino acids and α-hydroxy acids are readily accepted. Amino acids with aliphatic residues, such as alanine, isoleucine, and methionine, are hydrolyzed with high enantioselectivity for the l-enantiomer ( E >100), but amino acids with aromatic residues such as phenylalanine and phenylglycine, and esters of α-hydroxy acids are hydrolyzed with low enantioselectivity ( E = 1–5). Immobilization of the enzyme in a gelatin matrix (gelozyme) leads to a marginal improvement in the enantioselectivity for these substrates. However, a dramatic improvement in enantioselectivity is observed for ethyl 2-hydroxy-4-oxo-4-phenylbutyrate ( E value increases from 4.5 to 19.5 with S-selectivity). Similarly, glycidate esters, such as ethyl trans-(±)-3-phenyl glycidate and methyl trans-(±)-3-(4-methoxyphenyl) glycidate, are selectively hydrolyzed with a remarkable selectivity towards the (2 S,3 R)-enantiomer providing unreacted (2 R,3 S)-glycidate esters (ee >99%, conversion 52–55%) by the immobilized enzyme.

Use of Aspergillus oryzae protease for the resolution of α-hydroxy acids by enantioselective ester hydrolysis

The enzymatic hydrolysis of esters of α-hydroxy acids as non-amino acid substrates for microbial proteases was investigated. The methyl esters of 3-phenyllactic acid and its ring-substituted derivative were hydrolyzed with excellent enantioselectivities (E>110) using Aspergillus oryzae protease to give the (S)-acids. By contrast, only low enantioselectivities (E∼1) were obtained with the esters of mandelic acid. A gram-scale resolution of 3-phenyllactic acid was achieved by adopting this procedure, to afford the (S)-acid with 96% e.e. in 67% yield after recrystallization.

A Novel Access to 2‐Aminofuranones via Cyclization of Functionalized γ‐Hydroxy‐α,β‐butenoates Derived from N‐Hydroxybenzotriazole Esters of α‐Hydroxy Acids.

A Novel Access to 2‐Aminofuranones via Cyclization of Functionalized γ‐Hydroxy‐α,β‐butenoates Derived from N‐Hydroxybenzotriazole Esters of α‐Hydroxy Acids.

Ethyl 2,4-Dioxo-4-phenylbutyrate:A Versatile Intermediate for the Large-Scale Preparation of EnantiomericallyPure α-Hydroxy and α-Amino Acid Esters

Starting from ethyl 2,4-dioxo-4-phenylbutyrate, both enantiomers of six enantiomerically pure α-hydroxy and α-amino acid esters (homophenylalanine derivatives) were prepared on >100 g scale. The key step involves a Pt-cinchona catalyzed enantioselective hydrogenation followed by enrichment via crystallization. All derivatives are commercially available.

A Novel Access to 2-Aminofuranones via Cyclization of Functionalized γ-Hydroxy-α,β-butenoates Derived fromN-Hydroxybenzotriazole Esters of α-Hydroxy Acids

The reaction between the N-hydroxybenzotriazole esters of substituted glycolic acids and alkyl cyanoacetates or malononitrile leads to the synthesis of γ-hydroxy-functionalized butenoates which are cyclized under mild conditions to the corresponding 2-amino-3,5-disubstituted-4-furanones. That the products are optically active is confirmed by measurements of their optical rotations. On the other hand, replacement of N-hydroxybenzotriazole by N-hydroxysuccinimide might lead to by-products depending on the functionalized glycolic acid used.

Assessment of Topical Hypopigmenting Agents on Solar Lentigines of Asian Women

Background: So-called darkened age spots encompass distinct pathological processes. The efficacy of topical depigmenting agents is difficult to objectivate. Objective: To assess the hypopigmenting effect of three cosmetic formulations using objective biometrological methods. Methods: 50 women of South-East Asian ancestry were enrolled in this pilot study. They had solar lentigines according to dermoscopic criteria. The lesions were treated by topical hypopigmenting formulations. Products were applied twice daily for 2 or 3 months. Assessments at 1-month intervals were made using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection and photodensitometry- and image-analysis-assisted corneomelametry. Results: A 20% azelaic acid formulation and another one containing 5% ascorbyl glucosamine, 1% kojic acid and α-hydroxyacid esters appeared inefficacious on solar lentigines. A stabilized soy extract showed a better although modest lightening effect when assessed by corneomelametry. The subclinical or faint mottled skin revealed by ultraviolet light examination better responded (p < 0.05) to treatments. Conclusion: Focal epidermal hyperpigmentation is better controlled by topical whitening agents when the increase in melanin content reflects a modest functional hyperactivity of melanocytes.

InCl 3-Catalyzed direct aldol reactions of glyoxylic acid monohydrate and glyoxylates with various ketones: scope and limitations

The direct aldol reactions of various ketones with glyoxylic acid and glyoxylates afforded the α-hydroxy acid and α-hydroxy esters in good yields and high regioselectivities.

Dynamic kinetic resolution of alpha-hydroxy acid esters

[formula: see text] Enzymatic resolution in combination with ruthenium-catalyzed racemization of the substrate led to dynamic kinetic resolution of alpha-hydroxy esters in good yields and excellent ee's. Studies of different parameters showed that the best results were obtained using Pseudomonas cepacia lipase, ruthenium catalyst 3, and 4-chlorophenyl acetate as acyl donor in cyclohexane.

Aminolysis of α-hydroxy acid esters with α-amino acid salts; first step in the synthesis of optically active 2,5-morpholinediones

Aminolysis of α-hydroxy acid esters with α-amino acid salts; first step in the synthesis of optically active 2,5-morpholinediones

A new optical resolution method: coordinative resolution of mandelic acid esters. The crystal structure of calcium hydrogen (2R,3R)-O,O′-dibenzoyl tartrate–2(R)-(–)-methyl mandelate

A new and efficient resolution, based on the finding that the calcium acid salt of O,O′-dibenzoyltartaric acid forms crystalline coordination complexes with enantiomers of α-hydroxy acid esters, is reported.

Enantiomer separation by chromatography with novel chiral stationary phases.

For enantiomer separation, gas and high-performance liquid chromatography with chiral stationary phases are very convenient methods. We have developed various novel chiral stationary phases, including amino acid esters, peptide esters, amides, urea derivatives, α-hydroxy acid esters and copper (II) complexes of Schiff's bases. We have accomplished the separation of a broad range of enantiomers ( amine, amino acid, dipeptide, carboxylic acid, hydroxy acid, alcohol, aminoalcohol, ester, nitrile and organophosphoroamidothioate etc.) with these phases.

Simultaneous determination of methyl esters of α-hydroxy and nonhydroxy fatty acids from brain cerebroside by fused-silica capillary gas chromatography

Simultaneous determination of methyl esters of α-hydroxy and nonhydroxy fatty acids from brain cerebroside by fused-silica capillary gas chromatography