Maleic Acid Derivatives Research Articles

Five new maleic and succinic acid derivatives from the mycelium of Antrodia camphorata and their cytotoxic effects on LLC tumor cell line.

Five new maleic and succinic acid derivatives were isolated from the mycelium of Antrodia camphorata. Their structures were determined by various spectroscopic means. Maleimide derivatives 2 and 3 showed appreciable cytotoxic activity against LLC cells.

Stereospecific Synthesis of New 2,3,4,5‐Piperidinetetracarboxylic Acids and 2,3,5‐Piperidinetricarboxylic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and biological activity of isopentenyl diphosphate analogues

A series of analogues of isopentenyl diphosphate (IPP) having a dicarboxylate moiety in place of the diphosphate were synthesized and investigated as inhibitors of undecaprenyl diphosphate (UPP) synthase and protein farnesyltransferase (PFTase). PFTase is involved in control of cell proliferation and is known to be inhibited by certain maleic acid derivatives bearing long alkyl substituents (≥12 carbons, e.g., chaetomellic acid). UPP synthase is a potential target for antimicrobial agents and utilizes isopentenyl diphosphate (IPP) as a substrate. A number of dicarboxylate-containing IPP analogues were prepared in 2–5 steps from commercially available starting materials with good overall yield (20–78%). These syntheses involved the conjugate addition of an organocuprate to dimethyl acetylenedicarboxylate (DMAD) followed by basic ester hydrolysis. The E-pentenylbutanedioic acid 32 showed inhibition of UPP synthase with an IC 50 of 135 μM. Compound 30 displays competitive inhibition of PFTase with a K i of 287 μM.

Stereospecific synthesis of new 2,3,4,5-piperidinetetracarboxylic acids and 2,3,5-piperidinetricarboxylic acids

Diels–Alder adducts of 1,2-dihydropyridine with maleic and acrylic acid derivatives were stereospecifically converted by way of RuO4 oxidation into new r-2,c-3,c-4,c-5-piperidinetetracarboxylic acid, r-2,t-3,t-4,c-5-piperidinetetracarboxylic acid, r-2,c-3,c-5-piperidinetricarboxylic acid, and r-2,t-3,c-5-piperidinetricarboxylic acid.

PH‐dependent cyclodextrin capillary electrophoresis resolution of atropisomers

Five noncommercial and four commercially available cyclodextrin (CD) derivatives were tested as chiral auxiliaries for the capillary electrophoretic (CE) resolution of racemic 1,1'-bi-(2-naphthol) (BN), 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (BNHP), and 1,1'-binaphthyl-2,2'-diamine (BNA) at pH 4.0, 6.5, and 8.6. The noncommercial CDs were ethyloxycarbonyl-gamma-CD (ethylcarbonate-gamma-CD), dimethylamino ethyloxycarbonyl-beta-CD, a mercaptosuccinic acid derivative of beta-CD, a maleic acid derivative of beta-CD and heptakis(6-deoxy-6-amino)-beta-CD derivative with one amino group on the C-6 carbon of each glucose unit. Except for the latter, the remaining derivatives were synthesized for this work. Also commercially available methyl-beta-CD, hydroxypropyl-beta-CD and the native beta- and gamma-CDs were examined. Among the nine CDs tested, the maleic acid derivative of beta-CD gave the most interesting performances, since it resolved the atropisomers of BNA and BNHP in the same electrophoretic run at pH 4.0. It resolved the BNA racemate also at pH 6.5. Both the negatively charged CD tested were found to resolve anionic BNHP enantiomers, while positively charged CDs did not with cationic BNA. Several of the CDs investigated in this work were found to resolve the BNHP racemate, although at nonoptimal concentration. None of the experimented CDs was found to resolve the electrically neutral BN atropisomers pair at the three pHs considered, while some among these nine, experimented in a previous work, did so at higher pH.

A Method for Preparation of Unnatural (R)‐Malic Acid Derivatives with Phenylsilanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reversible and irreversible inhibitory activity of succinic and maleic acid derivatives on acetylcholinesterase.

Aryl succinic and maleic acid derivatives are potent inhibitors of bovine acetylcholinesterase in vitro. Succinic acid aminophenol derivatives 1b-e and 2b-d act as reversible inhibitors of acetylcholinesterase, while maleic acid aminophenol derivatives 3b-d and 4c-e act as choline subsite-directed irreversible inhibitors, detected by dialysis in the presence of edrophonium. Linear relationships between the logarithm of the velocity of hydrolysis of acetylcholine plotted against the time of incubation at several different inhibitor concentrations were determined. The K(i) for reversible competitive inhibitors was determined. For irreversible inhibitors the K(i) for the dissociation constant of the enzyme-inhibitor complex at the beginning of the recognition process was also determined as well as the inactivation constant of the enzyme-inhibitor adduct formation k(+2) and the bimolecular inhibition constant k(i) for the inhibition of acetylcholinesterase by aminophenol derivatives 3b-d and 4c-e. The conclusions of this study can be summarized as follows for both families: (a) the aromatic moiety played a critical role in the recognition of the active site; (b) in case of the reversible inhibitor, when the ester function took the place of the hydroxyl fragment, there was an important increase in the affinity; and (c) the distance between phenolic hydroxyl and nitrogen was critical because the inhibition is ortho<<meta<para.

A Method for Preparation of Unnatural (R)-Malic Acid Derivatives with Phenylsilanes

Enantiomerically pure unnatural (R)-malic acid derivatives were prepared from (R,R)-tartrates via their cyclic thionocarbonate derivatives using phenylsilanes in high isolated yields.

Graphical Abstracts

Synth. Commun. 2003, 33, 515 A Method for Preparation of Unnatural ( R )-Malic Acid Derivatives with PhenylsilaneS Dae Hyan Cho, Seong Ho Song, and Doo Ok Jang* Department of Chemistry, Yonsei University, Wonju, 222-710, Korea Enantiomerically pure unnatural (R)-malic acid derivatives were prepared from (R,R)-tartrates via their cyclic thionocarbonate derivatives using phenylsilanes in high isolated yields.

ChemInform Abstract: Regio‐ and Stereocontrolled Hydrocyanation of Chiral 2‐Alkylglycidamides with Et2AlCN: Synthesis of Enantiomerically Pure Mono‐ and Disubstituted Malic Acid Derivatives.

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New Results on the Stereoselective Alkylations of Malic Acid Derivatives Supported by Molecular Modeling

AbstractThe stereoselectivity of the alkylation of dialkyl malates is dependent on steric hindrance of both ester alkyl groups. It was found that the two alkyl groups have opposite effects on diastereoselectivity. Increased steric hindrance at the C(1) carboxy group increases the anti‐selectivity, whereas increased steric hindrance at the C(4) carboxy group decreases it. The results are explained by comparing the structures of the enolates, which were obtained by molecular modeling. Alkylation at C(4′) of dioxolanones, derived from benzyl‐substituted malic acids, with an additional stereogenic center on the side chain is dependent on the stereogenic centers of the ring acetal and of the side chain. Alkylation at low temperatures occurs only with cis‐dioxolanones having an (R)‐configured side‐chain stereogenic center. The corresponding trans‐dioxolanone and the cis‐dioxolanone with a (S)‐configured side‐chain stereogenic center were recovered unchanged. A rationale is presented with models of monolithiated dioxolanones obtained by ab initio calculations.

Endo and exo Ring fusion in the Diels–Alder reaction of 1-(2,4,6-trialkylphenyl-)3-methylphospholes with maleic acid derivatives

Diels–Alder reaction of the title phospholes and N-phenylmaleimide afforded, surprisingly, a mixture of endo and exo fused cycloadducts with the P-aryl substituent anti to the double bond giving, after oxidation the corresponding P-oxides. The P-center of the exo ring fused P-oxides was found to be inverted under the conditions of the oxidation. The cycloaddition of triisopropylphenylphosphole with N-methylmaleimide or with maleic acid anhydride gave the corresponding endo fused phosphanorbornenes affording stable products after oxidation. Relative stability of the possible isomers was evaluated experimentally and by quantum chemical calculations.

4+2] Versus [2+2] Cycloadditions in the Sphere of P-Heterocycles as Useful Synthetic Tools

The Diels-Alder reaction of 1,2-dihydrophosphinine oxides with dienophiles, such as dimethyl acetylenedicarboxylate (DM AD) and maleic acid derivatives affords phosphabicyclo [2. 2.2] oct adien es or bicyclooctenes, respectively, that are precursors of low-coordinated P-fragments, methylenephosphine oxides useful in the phosphorylation of alcohols, phenols and amines. An alternative mechanism involving an intermediate with a pentavalent, pentacoordinated phosphorus atom was also substantiated and proved. Reaction of the P-2, 4, 6-trialkylphenyl dihydrophosphinine oxides with DMAD followed an unexpected protocol to give the corresponding stabilised phosphonium ylides. The intermediates are oxaphosphetes formed by the [2+2] cycloaddition of the P=O group of the P-cycle and the triple bond of DMAD. This kind of reaction, that is the consequence of the presence of the electronreleasing trialkylphenyl group, has never been observed earlier and proved to be general to take place with a variety of cyclic phosphine oxides. Keywords: Cycloadditions, P-Heterocycles, 1,2-dihydrophosphinine oxides, acetylenedicarboxylate, methylenephosphine, oxaphosphetes, pentacoordinated phosphorus

Regio- and stereocontrolled hydrocyanation of chiral 2-alkylglycidamides with Et 2AlCN: synthesis of enantiomerically pure mono- and disubstituted malic acid derivatives

The opening of the oxirane ring of glycidamides with Et 2AlCN takes place under mild conditions in a completely regio- and stereoselective manner to afford β-cyano carboxamide derivatives, which are immediate precursors of mono- and disubstituted malic acid derivatives. The complete control of the regioselectivity can be rationalized as a consequence of the association of the reagent with the carboxamide group prior to intramolecular cyanide transfer.

New Phosphorus−Carbon Cage Compounds by Diels−Alder and Homo Diels−Alder Reactions of 1,3,5-Triphosphabenzenes with Alkenes

Ethylene, various monosubstituted alkenes (acrylic acid derivatives, styrene), as well as some selected disubstituted alkenes (maleic acid derivatives, fumaric acid derivatives, norbornene, cyclopentadiene) undergo Diels−Alder reactions with the 1,3,5-triphosphabenzenes 1 under mild conditions to furnish the dihydrotriphosphabarrelenes 9, 11a−c, 13a−e, 15a−d, 17a,b, and 24. The monoadduct 26 as well as the diadducts 27 and 28 are isolated following the reaction with norbornadiene. Cyclopropene is the only alkene to undergo a Diels−Alder/homo Diels−Alder reaction sequence to afford the hexacyclic system 20.

Enantioselective synthesis of α-hydroxylated enterolactone and analogs

A short and general synthesis of enantiomerically pure α-hydroxylated lactone lignans starting from commercially available iPr malate is presented. Key reactions are two stereoselective alkylations of malic acid derivatives. Some enhancements of the alkylation of malic acid esters and a general extension of the alkylation of dioxolanones is reported. Proof of the stereochemical outcome of the alkylation reactions is provided by X-ray diffraction analysis of α-hydroxy-α,β-dibenzyl-γ-butyrolactone, the first crystal structure of an enantiomerically pure α-hydroxylated lactone lignan.

Synthesis of (+)-wikstromol by double alkylation of malic acid

The synthesis of (+)-wikstromol in six steps, based on two stereoselective benzylations of unnatural malic acid derivatives, is presented. The influence of the alkyl ester on yield and selectivity in the alkylation of malic acid esters is examined.

Protective Effect of Maleic Acid Derivatives on the Properties of Wool Fabric Dyed at 120°C

Eleven maleic acid derivatives are synthesized and authenticated, then used as wool protective agents for dyeing wool at 120°C with Isolan Red S-RL. The protective effects are evaluated in terms of tensile properties (initial modulus, tensile strength, extension at break, and work to rupture) for both conditioned and wet-state fabrics, chemical damage is assessed in terms of alkali solubility, and hygral expansion is also measured. N-naphthyl and trifluorophenyl maleamic acid and N-benzyl and N-trifluorophenyl maleimides pro vide beneficial effects in terms of increased tensile strength, reduced hygral expansion, and minimal yellowing. However, N-benzyl and N-trifluorophenyl maleimides produce higher alkali solubilities. These results are in contrast to those for Irgasol HTW NEW treated wool, which has relatively low alkali solubility yet higher hygral expansion and poorer tensile properties.

Enzymatic methods for the preparation of enantiopure malic and aspartic acid derivatives in organic solvents

The kinetic resolution of malic and aspartic acid diesters as well as of its N-butanoyl dimethyl ester by highly regioselective lipases and acylase I enzymes were studied. Candida antarctica lipase A on Celite catalyzed the enantioselective acylation of the hydroxyl and amino groups. Acylase I from Aspergillus melleus and Candida antarctica lipase B catalyzed the enantioselective alcoholyses of the ester groups at the α- and β-positions, respectively.

Preparation of tricyclic nitrogen heterocycles via intramolecular Diels-Alder reaction of furans

Preparation of rigid tricyclic nitrogen heterocycles through acylation of N-alkylfurfurylamines with fumaric and maleic acid derivatives has been studied. The reaction proceeds via an initial amide formation followed by an intramolecular Diels-Alder (IMDA) reaction. Various acylation conditions have been studied. Influence of steric and electronic effects on the product formation has also been investigated.