Α-hydroxy Acids Research Articles

Thermo analytical study of phase transformation of TiO2 nanoparticles prepared using mono and di α-hydroxy acid water-soluble precursor by hydrothermal technique

ABSTRACT In this article, the isoconversional crystallization behavior of TiO2 nanoparticles prepared using titanium glycolate and titanium malate water-soluble precursors at alkaline and acidic conditions was investigated. Thermal decomposition experiments were carried out using thermo gravimetric (TG) analysis and the phase structure was determined by powdered X-ray diffraction (PXRD) analysis. The phase stability of the TiO2 NPs prepared using titanium malate complex was found to be better than that prepared using titanium glycolate water-soluble complex, especially in terms of loss in weight per cent and decomposition analysis. Apparent activation energies were also determined for both the samples prepared at pH 2, 4, 6, 8, 10 and 12. These results showed the ability of primary and secondary nucleation in shifting decomposition temperature that in turn increases the phase transformation temperature, by minimizing the energy through fraction reacted required to reach the crystalline state.

Effect of dentin biomodification delivered by experimental acidic and neutral primers on resin adhesion

ObjectivesProanthocyanidins (PACs) are biocompounds mimicking native collagen cross-links. The effective and practical delivery of any biocompound is pivotal for clinical usage. The aim was to investigate the dentin biomodification and effective formation of dentin–resin biointerfaces of two highly bioactive PAC-rich extracts, Vitis vinifera (Vv) and Camellia sinensis (Cs), delivered using neutral (NP) or acidic (AP) rinse-out primer approaches. MethodsThe depth of dentin demineralization (optical profilometry), dentin biomodification (apparent modulus of elasticity, collagen auto-fluorescence) and properties of dentin–resin interfaces (microtensile bond strength - μTBS, and micro-permeability) were investigated. NP consisted of either 15% Vv or Cs applied for 60 s after surface etching; while AP contained 15% Vv or Cs in either 35% glycolic acid or tartaric acid applied for 30 s or 60 s. Data were analyzed using ANOVA and post-hoc tests (α = 0.05). ResultsThe depth of demineralization was statistically higher when applied for 60 s, regardless of rinse-out primer approach (p < 0.001). Compared to the AP strategy, NP exhibited statistically higher apparent modulus of elasticity, regardless of PAC extract (p < 0.001). Highest μTBS were obtained for NPVv, which were statistically similar to APGAVv, when applied for 60 s (p < 0.001); both resulted in a dramatic decrease of the interfacial permeability. NPCs group showed the lowest μTBS (p < 0.001). ConclusionsA combination of high bond strength and low micro-permeability can be accomplished using glycolic acid with the mid- and high-PAC oligomer enriched extract (Vv). Cs extract containing mostly catechins and dimeric PACs, was found unsuitable for resin-dentin adhesion despite exhibiting high initial dentin biomodification. Clinical significanceThis study provides a new conceptual delivery of PAC-mediated dentin biomodification and conservative dentin surface etching using rinse-out primers. The strategy requires a specific combination of PAC source, α-hydroxy acid, and application time.

Inclusion of isolated α-amino acids along the polylactide chain through organocatalytic ring-opening copolymerization

Degradable polymers based on α-hydroxy acids and α-amino acids constitutes a potent class of biomaterials, combining high hydrolyzability with structural features that mimics peptides. Driven by the design criteria to construct isolated α-amino acid units along a main polylactide chain, a copolymer system was developed based on two monomers with distinctly different equilibrium behaviors. This was uncovered by detailed understanding on the kinetic and thermodynamic polymerizability of 3S,6S-dimethylmorpholine-2,5-dione (DMMD) and L-lactide (LLA) at low reaction temperatures. Under Brønsted base-promoted ring-opening copolymerization (ROCOP) conditions, the equilibrium nature of the copolymerization was shown susceptible to changes in the system, such as catalyst basicity, solvent polarity and initial monomer concentrations. Subsequently, high equilibrium conversions of both monomers with control over molecular weight and dispersity could be achieved within short reaction times by modulation of these factors. Thermodynamic elucidations of the copolymerization system revealed that DMMD behaved as an unstrained monomer with a large propagation barrier, favored by an increase in polymerization temperature. Ultimately, the high propagation barrier of DMMD in the system resulted in a kinetically controlled mechanism with the formation of completely isolated units of DMMD along the polylactide backbone. These results extend current ROCOP strategies of morpholine-2,5-diones and cyclic esters to a mild and selective copolymerization platform for the construction of sequence-controlled α-amino acid decorated polyesters for medical applications.

Bioerodible Hydrogels Based on Photopolymerized Poly(ethylene glycol)-co-poly(α-hydroxy acid) Diacrylate Macromers

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTBioerodible Hydrogels Based on Photopolymerized Poly(ethylene glycol)-co-poly(α-hydroxy acid) Diacrylate MacromersLaura J. MacdougallLaura J. MacdougallMore by Laura J. Macdougall and Kristi AnsethKristi AnsethMore by Kristi Ansethhttp://orcid.org/0000-0002-5725-5691Cite this: Macromolecules 2020, 53, 7, 2295–2298Publication Date (Web):April 14, 2020Publication History Received6 January 2020Revised3 February 2020Published online14 April 2020Published inissue 14 April 2020https://doi.org/10.1021/acs.macromol.0c00030Copyright © 2020 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3074Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (970 KB) Get e-AlertsSUBJECTS:Alcohols,Biomaterials,Degradation,Hydrogels,Photopolymerization Get e-Alerts

Evaluating the Risk Factors of Post Inflammatory Hyperpigmentation Complications with Nd-YAG Laser Toning Using LASSO-Based Algorithm

The neodymium-doped yttrium aluminum garnet (Nd-YAG) laser is used for removal of pigmented skin patches and rejuvenation of skin. However, complications such as hyperpigmentation, hypopigmentation, and petechiae can occur after frequent treatments. Therefore, identifying the risk factors for such complications is important. The development of a multivariable logistic regression model with least absolute shrinkage and selection operator (LASSO) is needed to provide valid predictions about the incidence of post inflammatory hyperpigmentation complication probability (PIHCP) among patients treated with Nd-YAG laser toning. A total of 125 female patients undergoing laser toning therapy between January 2014 and January 2016 were examined for post-inflammatory hyperpigmentation (PIH) complications. Factor analysis was performed using 15 potential predictive risk factors of PIH determined by a physician. The LASSO algorithm with cross-validation was used to select the optimal number of predictive risk factors from the potential factors for a multivariate logistic regression PIH complication model. The optimal number of predictive risk factors for the model was five: immediate endpoints of laser (IEL), α-hydroxy acid (AHA) peels, Fitzpatrick skin phototype (FSPT), acne, and melasma. The area under the receiver operating characteristic curve (AUC) was 0.79 (95% CI, 0.70–0.88) in the optimal model. The overall performance of the LASSO-based PIHCP model was satisfactory based on the AUC, Omnibus, Nagelkerke R2, and Hosmer–Lemeshow tests. This predictive risk factor model is useful to further optimize laser toning treatment related to PIH. The LASSO-based PIHCP model could be useful for decision-making.

Determination of ten kinds of α-hydroxy acids in cosmetics with quantitative analysis of multi-components by single marker

To establish a method for determination of ten kinds of α-hydroxy acids in cosmetics with quantitative analysis of multi-components by single marker(QAMS). The analytes were separated by high performance liquid chromatography on a Venusil XBP C_8 column(4. 6 mm×250 mm, 5 μm), with the mobile phases of ammonium dihydrogen phosphate buffer-methonal under a gradient elution. The components were detected at the wavelengths of 214 nm using a diode array detector. Citric acid was used as the internal standard to determine the relative correction factors(RCFs) of the nine other α-hydroxy acids, in order to calculate their contents in samples by their RCFs. Good linearity with correlation coefficients greater than 0. 9994 was obtained for all the analytes. Stabilities within 24 h and precision of ten α-hydroxy acids were all good. Recoveries of the method were from 89. 3% to 105. 0% at three concentration levels, with the relative standard deviation(RSD) from 1. 0% to 2. 9%. Nine batches of samples were determined by QAMS, as well as the standard curve method(SCM). The relative average deviations(RAD) were below 3. 2% between the result of the two method, which showed good feasibility and accuracy of QAMS. The method is simple, accurate and beneficial to the saving of reference substances, which is suitable for the determination of ten kinds of α-hydroxy acids in cosmetics.

Chemoselective Catalytic α-Oxidation of Carboxylic Acids: Iron/Alkali Metal Cooperative Redox Active Catalysis.

We developed a chemoselective catalytic activation of carboxylic acid for a 1e- radical process. α-Oxidation of a variety of carboxylic acids, which preferentially undergo undesired decarboxylation under radical conditions, proceeded efficiently under the optimized conditions. Chemoselective enolization of carboxylic acid was also achieved even in the presence of more acidic carbonyls. Extensive mechanistic studies revealed that the cooperative actions of iron species and alkali metal ions derived from 4 Å molecular sieves substantially facilitated the enolization. For the first time, catalytic enolization of unprotected carboxylic acid was achieved without external addition of stoichiometric amounts of Brønsted base. The formed redox-active heterobimetallic enediolate efficiently coupled with free radical TEMPO, providing synthetically useful α-hydroxy and keto acid derivatives.

Oxalyl-CoA Decarboxylase Enables Nucleophilic One-Carbon Extension of Aldehydes to Chiral α-Hydroxy Acids.

The synthesis of complex molecules from simple, renewable carbon units is the goal of a sustainable economy. Here we explored the biocatalytic potential of the thiamine‐diphosphate‐dependent (ThDP) oxalyl‐CoA decarboxylase (OXC)/2‐hydroxyacyl‐CoA lyase (HACL) superfamily that naturally catalyzes the shortening of acyl‐CoA thioester substrates through the release of the C1‐unit formyl‐CoA. We show that the OXC/HACL superfamily contains promiscuous members that can be reversed to perform nucleophilic C1‐extensions of various aldehydes to yield the corresponding 2‐hydroxyacyl‐CoA thioesters. We improved the catalytic properties of Methylorubrum extorquens OXC by rational enzyme engineering and combined it with two newly described enzymes—a specific oxalyl‐CoA synthetase and a 2‐hydroxyacyl‐CoA thioesterase. This enzymatic cascade enabled continuous conversion of oxalate and aromatic aldehydes into valuable (S)‐α‐hydroxy acids with enantiomeric excess up to 99 %.

Vascular Wall-Mesenchymal Stem Cells Differentiation on 3D Biodegradable Highly Porous CaSi-DCPD Doped Poly (α-hydroxy) Acids Scaffolds for Bone Regeneration.

Vascularization is a crucial factor when approaching any engineered tissue. Vascular wall–mesenchymal stem cells are an excellent in vitro model to study vascular remodeling due to their strong angiogenic attitude. This study aimed to demonstrate the angiogenic potential of experimental highly porous scaffolds based on polylactic acid (PLA) or poly-e-caprolactone (PCL) doped with calcium silicates (CaSi) and dicalcium phosphate dihydrate (DCPD), namely PLA-10CaSi-10DCPD and PCL-10CaSi-10DCPD, designed for the regeneration of bone defects. Vascular wall–mesenchymal stem cells (VW-MSCs) derived from pig thoracic aorta were seeded on the scaffolds and the expression of angiogenic markers, i.e. CD90 (mesenchymal stem/stromal cell surface marker), pericyte genes α-SMA (alpha smooth muscle actin), PDGFR-β (platelet-derived growth factor receptor-β), and NG2 (neuron-glial antigen 2) was evaluated. Pure PLA and pure PCL scaffolds and cell culture plastic were used as controls (3D in vitro model vs. 2D in vitro model). The results clearly demonstrated that the vascular wall mesenchymal cells colonized the scaffolds and were metabolically active. Cells, grown in these 3D systems, showed the typical gene expression profile they have in control 2D culture, although with some main quantitative differences. DNA staining and immunofluorescence assay for alpha-tubulin confirmed a cellular presence on both scaffolds. However, VW-MSCs cultured on PLA-10CaSi-10DCPD showed an individual cells growth, whilst on PCL-10CaSi-10DCPD scaffolds VW-MSCs grew in spherical clusters. In conclusion, vascular wall mesenchymal stem cells demonstrated the ability to colonize PLA and PCL scaffolds doped with CaSi-DCPD for new vessels formation and a potential for tissue regeneration.

Polyesters as a Model System for Building Primitive Biologies from Non-Biological Prebiotic Chemistry.

A variety of organic chemicals were likely available on prebiotic Earth. These derived from diverse processes including atmospheric and geochemical synthesis and extraterrestrial input, and were delivered to environments including oceans, lakes, and subaerial hot springs. Prebiotic chemistry generates both molecules used by modern organisms, such as proteinaceous amino acids, as well as many molecule types not used in biochemistry. As prebiotic chemical diversity was likely high, and the core of biochemistry uses a rather small set of common building blocks, the majority of prebiotically available organic compounds may not have been those used in modern biochemistry. Chemical evolution was unlikely to have been able to discriminate which molecules would eventually be used in biology, and instead, interactions among compounds were governed simply by abundance and chemical reactivity. Previous work has shown that likely prebiotically available α-hydroxy acids can combinatorially polymerize into polyesters that self-assemble to create new phases which are able to compartmentalize other molecule types. The unexpectedly rich complexity of hydroxy acid chemistry and the likely enormous structural diversity of prebiotic organic chemistry suggests chemical evolution could have been heavily influenced by molecules not used in contemporary biochemistry, and that there is a considerable amount of prebiotic chemistry which remains unexplored.

The Generation of the Oxidant Agent of a Mononuclear Nonheme Fe(II) Biomimetic Complex by Oxidative Decarboxylation. A DFT Investigation.

The oxidative decarboxylation of the iron(II) α-hydroxy acid (mandelic acid) complex model, biomimetic of Rieske dioxygenase, has been investigated at the density functional level. The explored mechanism sheds light on the role of the α-hydroxyl group on the dioxygen activation. The potential energy surfaces have been explored in different electronic spin states. The rate-determining step of the process is the proton transfer. The oxidative decarboxylation preferentially takes place on the quintet state.

α-Hydroxy acid as an aldehyde surrogate: metal-free synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and other N-heterocycles via decarboxylative oxidative annulation reaction.

A metal-free and efficient procedure for the synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and indolo[1,2-a]quinoxaline has been developed. The key features of our method include the in situ generation of aldehyde from α-hydroxy acid in the presence of TBHP (tert-butyl hydrogen peroxide), and further condensation with various amines, followed by intramolecular cyclization and subsequent oxidation to afford the corresponding quinoxalines, quinazolinones derivatives in moderate to high yields.

Photocatalytic decarboxylative alkenylation of α-amino and α-hydroxy acid-derived redox active esters by NaI/PPh3 catalysis.

Herein, we report the photocatalytic decarboxylative alkenylation reactions of N-(acyloxy)phthalimide derived from α-amino and α-hydroxy acids with 1,1-diarylethene, and with cinnamic acid derivatives through double decarboxylation, using sodium iodide and triphenylphosphine as redox catalysts. The reaction proceeds under mild irradiation conditions with visible blue light (440 nm or 456 nm) in an acetone solvent without recourse to transition-metal or organic dye based photoredox catalysts. The reaction proceeds via photoactivation of a transiently self-assembled chromophore from N-(acyloxy)phthalimide and NaI/PPh3. Solvation plays a crucial role in the reactivity.

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).

Solid-state conformations of linear depsipeptide amides with an alternating sequence of α,α-disubstituted α-amino acid and α-hydroxy acid.

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α-disubstituted α-amino acid and an α-hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)-Pms-Acp-(S)-Pms-Acp-(S)-Pms-Acp-NMe2 acetonitrile solvate, C47H58N4O9·C2H3N, (3b), as well as in the related linear tetradepsipeptide amide (S)-Pms-Aib-(S)-Pms-Aib-NMe2, C28H37N3O6, (5a), the diastereoisomeric mixture (S,R)-Pms-Acp-(R,S)-Pms-Acp-NMe2/(R,S)-Pms-Acp-(R,S)-Pms-Acp-NMe2 (1:1), C32H41N3O6, (5b), and (R,S)-Mns-Acp-(S,R)-Mns-Acp-NMe2, C30H37N3O6, (5c) (Pms is phenyllactic acid, Acp is 1-aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a β-turn conformation in the solid state, which is stabilized by intramolecular N-H...O hydrogen bonds. Whereas β-turns of type I (or I') are formed in the cases of (3b), (5a) and (5b), which contain phenyllactic acid, the torsion angles for (5c), which incorporates mandelic acid, indicate a β-turn in between type I and type III. Intermolecular N-H...O and O-H...O hydrogen bonds link the molecules of (3a) and (5b) into extended chains, and those of (5a) and (5c) into two-dimensional networks.

A New Synthetic Pathway for the Bioproduction of Glycolic Acid From Lignocellulosic Sugars Aimed at Maximal Carbon Conservation.

Glycolic acid is a two-carbon α-hydroxy acid with many applications in industrial sectors including packaging, fine chemistry, cosmetics, and pharmaceutics. Currently, glycolic acid is chemically manufactured from fossil resources. This chemical mode of production is raising some concerns regarding its use in health for personal care. Microbial production of GA stands as a remarkable challenge to meet these concerns, while responding to the increasing demand to produce bio-sourced products from renewable carbon resources. We here report on the design and expression of a novel non-natural pathway of glycolic acid in E. coli. The originality of this new pathway, termed “glycoptimus” relies on two pillars. On the one hand, it requires the overexpression of three naturally occurring E. coli genes, namely kdsD encoding a D-arabinose-5-P isomerase, fsaA encoding a class 1 aldolase that cleaves D-arabinose-5-P into glyceraldehyde-3-P and glycolaldehyde, and aldA coding for an aldehyde dehydrogenase that oxidizes glycoladehyde in glycolate. These three genes constitute the “glycoptimus module.” On the other hand, the expression of these genes together with a reshaping of the central carbon metabolism should enable a production of glycolic acid from pentose and hexose at a molar ratio of 2.5 and 3, respectively, which corresponds to 50% increase as compared to the existing pathways. We demonstrated the ‘in vivo’ potentiality of this pathway using an E. coli strain, which constitutively expressed the glycoptimus module and whose carbon flow in glycolysis was blocked at the level of glyceraldehyde-3-P dehydrogenase reaction step. This engineered strain was cultivated on a permissive medium containing malate and D-glucose. Upon exhaustion of malate, addition of either D-glucose, D-xylose or L-arabinose led to the production of glycolic acid reaching about 30% of the maximum molar yield. Further improvements at the level of enzymes, strains and bioprocess engineering are awaited to increase yield and titer, rendering the microbial production of glycolic acid affordable for a cost-effective industrial process.

Fabrication of POX/PLGA Scaffold for the Potential Application of Tissue Engineering and Cell Transplantation

Poly lactic-co-glycolic acid (PLGA), a synthetic polymer, belongs to the fabrication of poly(α-hydroxy acid) systems approved by the US Food and Drug Administration. PLGA has been widely used in clinical applications due to its excellent biocompatibility, controlled biodegradability, and convenient processability. However, their degradation products cause inflammation, their rate of hydrolysis is slow, and the release rate of the drug is delayed. Therefore, polyoxalate (POX), which is a biodegradable polymer, was used to overcome these problems. The amount of POX was gradually increased to reduce the toxicity of PLGA, and the degree of cell proliferation was confirmed. In this study, POX/PLGA film in different composition was prepared and they were characterized using scanning electron microscope (SEM). Fourier-transform infrared spectroscopy (FTIR), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and real-time polymerase chain reaction (RT-PCR). Among the different combination studied, 50% POX/PLGA film showed better results for all the analyses performed compared with other scaffolds, when the National Institute of Health (NIH)/3T3 mouse embryo fibroblasts were cultured in vitro. We confirmed that 50% POX/PLGA film can be applied in different tissue engineering fields including bone tissue engineering and drug delivery applications.

Dl-Malic acid as a component of α-hydroxy acids: effect on 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in vitro and in vivo

Background: dl-Malic acid (dl-M) is used widely in cosmetic formulations as a pH-adjuster or as a preservative. dl-M is used as an exfoliator in the form of α-hydroxy acids. However, the role of dl-M in skin diseases (including atopic dermatitis (AD)) has not been studied deeply. We wished to reveal the effect of dl-M on AD induced by 2,4-dinitrochlorobenzene (DNCB) in Balb/c mice.Methods: The thickness and immune-cell infiltration into the dermis and epidermis were evaluated. Moreover, serum levels of cytokines, as well as expression of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) in tissue were measured in AD mice. We also studied the effect of dl-M on inflammatory mediators in a human keratinocyte (HaCaT) cell line. Results: The dl-M (high) group improved skin condition compared with the DNCB-treated group. The dl-M (high) group inhibited phosphorylation of MAPK and NF-κB in skin tissue. dl-M reduced serum levels of interleukin-4 and IgE. Finally, dl-M decreased the expression of thymus and activation-regulated chemokine, monocyte chemoattractant protein-1 and intercellular cell adhesion molecule induced by interferon-gamma/tumor necrosis factor-α in HaCaT cells. Discussion: These results suggest that dl-M can improve the skin conditions of AD mice.

Highly functionalized five-membered bicyclic a-Hydroxy acids from synthetic equivalent of glycolic acids

Five-membered cyclic α-hydroxy acids (1-hydroxycycycloalkane-1-carboxylic acids) are important constituents in biologically active natural products and also important precursor molecules for the synthesis of pharmacologically active compounds. This paper presents stereo selective synthesis of polysubstituted five-membered bicyclic α-hydroxy acid derivatives from α, α, α-dialkylated 1,3-dixolan-4-one (9). The synthesis was initiated on the α-propagylation of 2-(tert-butyl)-5-(1-ethenylprop-2-enyl)-1, 3-dixololan-4-one (trans-8) via its enolate, followed by intramolecular Pauson-Khand cyclization. The reaction was stereo selective and afforded two isomers (10a and 10b) in 4:1 ratio out of four possible diastereoisomers of bicyclic α-hydroxy acid (bicyclic 1-hydroxycarboxylic acid) derivatives. This method opens a new avenue to prepare synthetically useful highly functionalized stereoselctive synthesis of five-membered bicyclic α-hydroxy acids using a convenient and very effective method.

Sacrificial Anode-Free Electrosynthesis of α-Hydroxy Acids via Electrocatalytic Coupling of Carbon Dioxide to Aromatic Alcohols

Electrocarboxylation of organic compounds using CO2 is a promising approach toward a sustainable low-carbon society, but it is desirable to avoid the use of conventional sacrificial anodes in terms of green chemistry. Here, we report a novel electrocarboxylation methodology operating in a simple undivided cell with a nonsacrificial anode, at which tetramethylpiperidine-1-oxyl (TEMPO)-mediated alcohol oxidation takes place. Aromatic alcohols can be oxidized with high efficiency to ketones or aldehydes at the anode in the presence of a small amount of water, and then converted to α-hydroxy acids in yields of up to 61% by coupling with CO2 at the cathode. The electrocarboxylation mechanism comprising electron and proton transfers at the cathode is discussed along with experiments using various cathode materials. Electron and proton transfers are influenced by the hydrogen adsorption energy of the cathode material, which plays an important role in the electrocarboxylation efficiency.