Glyoxylic Acid Derivatives Research Articles

Synthesis, characterization, crystal structure, electrochemical studies and biological evaluation of metal complexes with thiosemicarbazone of glyoxylic acid

Cobalt and nickel nitrates form with thiosemicarbazone of glyoxylic acid (H2GAT) complexes of empirical composition Co(C3H4N3O2S)2∙2H2O, Ni(C3H4N3O2S)2∙2H2O and Ni(C3H6N3O2S)2. X-ray diffraction studies have shown that the Co(HGAT)2∙2H2O, Ni(HGAT)2∙2H2O complexes are mononuclear, in which the coordination around the metal is octahedral, made up of two sulfur atoms, two nitrogen atoms and two oxygen atoms from two ligands. By the interaction of NiCl2·H2O with 2-[2-(aminothioxomethyl)hydrazinyl] acetic acid (H2TAA) instead of the expected the metal thiosemicarbazonate complex with the hydrogenated on the azomethine group ligand was obtained. The redox properties of these compounds were also investigated by voltammetry on Pt in dimethylsulfoxide/tetrabutylammonium perchlorate. These thiosemicarbazone of glyoxylic acid derivatives had effective inhibition against α-glycosidase, cytosolic carbonic anhydrase I and II isoenzymes, butyrylcholinesterase and acetylcholinesterase. Ki values were found as 26.12–36.58 nM for hCA I, 20.73–40.78 nM for hCA II, 184.30–642.18 nM for AChE, 123.67–342.37 nM for BChE, and 14.66–45.62 nM for α-glycosidase.

Palladium-Catalyzed Enantioselective Three-Component Synthesis of α-Arylglycines.

A general Pd-catalyzed, enantioselective three-component synthesis of α-arylglycines starting from sulfonamides, glyoxylic acid derivatives, and boronic acids was developed. This operationally straightforward procedure enables the preparation of a wide variety of α-arylglycines in high yields and excellent levels of enantioselectivity from a simple set of readily available starting materials. Incorporation of Pbf-amides gives a racemization-free access to N-unprotected α-arylglycines.

Copper‐Catalyzed Double Decarboxylative Coupling Reactions of Alkynyl Carboxylic Acid and Glyoxylic Acid: Synthesis of Propargyl Amines and Imidazopyridines

AbstractThe reaction of alkynyl carboxylic acids, glyoxylic acid derivatives, and amines in the presence of a copper catalyst afforded the corresponding propargyl amines in good yields. The alkynyl carboxylic acid of this coupling reaction shows similar reactivity to that of a terminal alkyne, and the reactivity of the glyoxylic acid is almost identical to that of an aldehyde. When 2‐aminopyridine was employed as the amine source, imidazopyridine derivatives were formed in good yields.

ChemInform Abstract: A Cascade Aza‐Cope/Aza‐Prins Cyclization Leading to Piperidine Derivatives.

AbstractA novel cascade aza‐Cope/aza‐Prins cyclization of homoallylamines (I) with formaldehyde and glyoxylic acid derivatives to give N‐substituted 4‐hydroxypiperidines is investigated.

A Van Leusen deprotection-cyclization strategy as a fast entry into two imidazoquinoxaline families

A concise synthesis of two pharmacologically relevant classes of molecules possessing the imidazoquinoxaline core is reported. The protocol involves use of 1,2-phenylenediamines and glyoxylic acid derivatives, namely ethyl glyoxylate or benzylglyoxamide, along with tosylmethylisocyanides in a microwave-assisted Van Leusen three-component condensation. Subsequent unmasking (Boc removal) of an internal amino-nucleophile promotes deprotection and cyclization that take place either spontaneously in a one-pot fashion to give 8 or upon acidic treatment under microwave irradiation after isolation of the imidazole intermediate to give 11. Of note, a tricyclic framework is hence assembled by means of a rapid and straightforward method with a high bond-forming efficiency.

ChemInform Abstract: Cationic Iron(III) Porphyrin‐Catalyzed [4 + 2] Cycloaddition of Unactivated Aldehydes with Simple Dienes.

Cationic iron(III) porphyrin was found to be an efficient catalyst for the highly chemoselective hetero-Diels–Alder-type reaction of aldehydes with 1,3-dienes. The catalyzed process did not require the use of electron-deficient aldehydes such as glyoxylic acid derivatives or activated electron-rich 1,3-dienes such as Danishefsky’s diene and Rawal’s diene. The high functional group tolerance and robustness of the catalyst were demonstrated. Further, the potential utility of the catalyst was demonstrated by performing the cycloaddition in the presence of water and by carrying out cycloaddition of an unactivated ketone such as cyclohexanone with a diene.

Cationic Iron(III) Porphyrin-Catalyzed [4 + 2] Cycloaddition of Unactivated Aldehydes with Simple Dienes

Cationic iron(III) porphyrin was found to be an efficient catalyst for the highly chemoselective hetero-Diels-Alder-type reaction of aldehydes with 1,3-dienes. The catalyzed process did not require the use of electron-deficient aldehydes such as glyoxylic acid derivatives or activated electron-rich 1,3-dienes such as Danishefsky's diene and Rawal's diene. The high functional group tolerance and robustness of the catalyst were demonstrated. Further, the potential utility of the catalyst was demonstrated by performing the cycloaddition in the presence of water and by carrying out cycloaddition of an unactivated ketone such as cyclohexanone with a diene.

ChemInform Abstract: syn‐Selective Asymmetric Cross‐Aldol Reactions Between Aldehydes and Glyoxylic Acid Derivatives Catalyzed by an Axially Chiral Amino Sulfonamide.

AbstractThe cross‐aldol products (III), (V) and (VII) are highly functionalized and readily converted to synthetically useful and important chiral building blocks such as γ‐lactone (VIII) and γ‐lactam (X).

Syn-Selective asymmetric cross-aldol reactions between aldehydes and glyoxylic acid derivatives catalyzed by an axially chiral amino sulfonamide

syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl glyoxylate and glyoxamide were realized by the use of an axially chiral amino sulfonamide (S)-1. The cross-aldol products obtained are densely functionalized and readily converted to synthetically useful and important chiral building blocks such as γ-lactone and γ-lactam.

Synthesis of chiral 4-substituted 2-hydroxypent-4-enoic acid derivatives via diastereoselective ene reaction promoted by ZnBr 2

The diastereoselective carbonyl-ene reaction of various 1,1-disubstituted olefins with the chiral derivatives of glyoxylic acid, with Oppolzer’s sultam 1a and 8-phenylmenthol 1b auxiliaries, was studied. The reaction proceeds effectively under undemanding conditions in the presence of equimolar or catalytic amount of ZnBr 2 in good yield and at 72–94% de. Diastereoselectivities are usually slightly better with 8-phenylmenthyl glyoxylate 1b, however, the use of hemiacetal 1a is preferred because the products are often crystalline.

Stereochemistry of the Diels–Alder reaction at high pressure: diastereo- and enantioselective [4+2]cycloaddition of buta-1,3-diene to glyoxylic acid derivatives catalysed by (salen) chromium(III) complexes

High-pressure [4+2]cycloadditions of buta-1,3-diene 1 to chiral 2a– c and achiral 7a– c glyoxylates, in the presence of (salen) chromium(III) complexes 5 and 6, were studied. The influence of such chiral Lewis acids on diastereoselectivity or enantioselectivity of the cycloaddition was investigated; a moderate asymmetric induction for both diastereo- and enantioselective variants of the cycloaddition was observed (up to 58% de and up to 71% ee, respectively).

1,5-Diarylpyrrole-3-acetic Acids and Esters as Novel Classes of Potent and Highly Selective Cyclooxygenase-2 Inhibitors

A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.

Synthesis of glyoxylyl peptides using an Fmoc-protected α,α′-diaminoacetic acid derivative

The synthesis of glyoxylyl peptides by coupling the masked glyoxylic acid derivative (FmocNH)(2)CHCO(2)H, 1, to a peptidyl resin assembled using Fmoc/tert-butyl chemistry has been described recently. Deprotection and cleavage of the peptide from the solid support using TFA was followed by unmasking of the glyoxylyl group in solution in the presence of DBU. [] The glyoxylyl peptide was thus generated using non-oxidizing conditions by comparison with the method based on the periodic oxidation of a seryl-precursor. However, base treatment of the (FmocNH)(2)CHCO(2)-peptide led to the formation of a byproduct besides the desired glyoxylyl peptide. This paper describes an optimized procedure for unmasking the Fmoc-protected alpha,alpha'-diaminoacetic acid moiety in solution which suppressed byproduct formation. Also presented is a series of experiments that permitted a structure and a mechanism of formation for the byproduct to be suggested.

Highly Diastereoselective Henry Reaction of Nitro Compounds with Chiral Derivatives of Glyoxylic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly diastereoselective Henry reaction of nitro compounds with chiral derivatives of glyoxylic acid

N-Glyoxyloyl-(2 R)-bornane-10,2-sultam and (1 R)-8-phenylmenthyl glyoxylate react stereoselectively with simple nitro compounds giving diastereoisomeric nitroalcohols with high asymmetric induction. N-Glyoxyloyl-(2 R)-bornane-10,2-sultam 1a is shown to be a highly efficient chiral inducer, superior to (1 R)-8-phenylmenthyl glyoxylate 1b . In all cases, the absolute (2 S) configuration at the center bearing the hydroxy group and the relative syn configuration for the major diastereoisomers were determined.

Diastereoselective Reaction of Buta‐1,3‐diene with Chiral Derivatives of Glyoxylic Acid: Effective Route to Optically Pure 2‐Substituted 3,6‐Dihydro‐2H‐pyrans.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly diastereoselective nitroaldol reactions with chiral derivatives of glyoxylic acid

N-Glyoxyloyl-( 2R)-bornane-10,2-sultam ( 1a ) and (1 R)-8-phenylmenthyl glyoxylate ( 1b ) react stereoselectively with simple nitroalkanes giving diastereomeric nitroalcohols with high asymmetric induction. The glyoximide 1a is proved to be a highly efficient chiral inducer, superior to glyoxylate 1b . In all cases, the absolute configuration (2 S) and relative configuration, syn for the major diastereoisomers, were confirmed.

Asymmetric Morita–Baylis–Hillman reaction of chiral glyoxylates

The first Morita–Baylis–Hillman reaction of chiral glyoxylic acid derivatives, i.e. N-glyoxyloyl-(2 R)-bornane-10,2-sultam and (−)-8-phenylmenthyl glyoxylate is described. The reaction with cyclic α,β-unsaturated ketones proceeded under the catalytic influence of dimethyl sulfide in the presence of titanium tetrachloride. The adducts were obtained with very high diastereoisomeric excess (over 95% d.e.) and typical yields of 78%. The absolute configuration of the newly created stereogenic center was established by X-ray crystallographic analysis.

Synthesis of 2-(1-alkyl(aryl)-4-oxo-5,6,7,8-tetrafluoro-1,4-dihydroquinolin-3-yl)glyoxylic acid derivatives

Methods for synthesis of previously unknown 2-(1-alkyl(aryl)-4-oxo-5,6,7,8-tetrafluoro-1,4-dihydroquinolin-3-yl)glyoxylic acids and their esters from the copper chelate of ethyl pentafluorobenzoylpyruvate were developed. 1-Aryl(alkyl)-3-ethoxalyl-5,6,7,8-tetrafluoro-quinolin-4-ones react with o-phenylenediamine and o-aminophenol to give the corresponding quinolin-3-ylquinoxalones and quinolin-3-ylbenzoxazines. The same heterocycles act with o-aminothiophenol to yield ethyl-2-(7-(2-aminophenylthio)-1-aryl-5,6,8-trifluoro-quinolon-3-yl)-2-(2-mercaptophenylimino)glioxylates. Interaction of 1-aryl-3-ethoxalyl-(heteryl)-5,6,7,8-tetrafluoroquinolones with morpholine gives 7-mono- and 5,7-disubstituted products depending on the reaction conditions.

Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives.

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by beta-bromo alcohols. The resulting esters undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a beta-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 --> 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the cyclization product.