Acrylic Acid Derivatives Research Articles

Molecular Imprinting: Synthesis of Polymer Particles with Antibody-like Binding Characteristics for Glucose Oxidase

A phosphate buffer containing a mixture of glucose oxidase, acrylic acid derivatives, N,N′-1,2 dihydroxy-ethylene-bis(acrylamide), N,N′-(methylene)-bisacrylamide and surface-modified silica was radically polymerized with (NH4)2S2O8. The polymer formed a thin layer around the silica beads. After sieving of these polymer particles, the surface bound protein was eluted. In rebinding assays and enzyme activity tests a specific binding capacity for glucose oxidase of up to 0.557 μg GOD/100 mg dry weight of polymer particles could be determined. These polymer particles have the potential to be used as specific separation or dectection material.

Mucoadhesive polymers in peroral peptide drug delivery. V. Effect of poly(acrylates) on the enzymatic degradation of peptide drugs by intestinal brush border membrane vesicles

The purpose of the study was to evaluate the inhibitory effect of the mucoadhesive poly(acrylates) polycarbophil and carbomer on the activity of proteolytic enzymes bound to the intestinal brush border. To that end, the degradation of a number of peptide drugs in the presence or absence of the poly(acrylates) was investigated, using rat brush border membrane vesicles (BBMV) as the protease preparation. Both carbomer and polycarbophil in concentrations of 0.25 and 0.5% (w/v) reduced rather weakly the enzymatic degradation of the peptide 9-desglycinamide, 8-arginine vasopressin (DGAVP), and only 0.5% (w/v) carbomer inhibited metkephamid degradation, but not polycarbophil. More pronounced inhibitory effects on DGAVP breakdown were found following a 30 min preincubation of the BBMV suspension with 0.5% (w/v) carbomer. However, the poly(acrylic acid) derivatives were unable to inhibit the degradation of buserelin at all. On the other hand, the polypeptide hormone insulin was remarkably stable in the BBMV preparations. In conclusion, the poly(acrylic acid) derivatives polycarbophil and carbomer show rather weak inhibitory effects on enzymes of the intestinal brush border cell membranes responsible for DGAVP and metkephamid degradation.

Poly(acrylic acid) derivatives and chitosans improve intestinal buserelin absorption invivo

Poly(acrylic acid) derivatives and chitosans improve intestinal buserelin absorption invivo

Uptake and Exudation of Phenolic Compounds by Wheat and Antimicrobial Components of the Root Exudate

In the course of our study, it was found that phenyl propenoic acid derivatives were readily taken up by wheat. Leaf leachate components were chosen for the feeding experiments and p-coumaric acid, ferulic acid and caffeic acid were found to be quickly taken up into the plants via the roots. The analytical study revealed that the exudate contained potent antimicrobial compounds together with amino acids and sugars. Besides the primary metabolites, 4-hydroxystyrene, 3-methoxy-4-hydroxystyrene and 3-methoxy-4-acetoxystyrene were identified as exudate components from wheat roots in sterile hydroponic culture. This indicates that these antimicrobial components may play a significant role in the defense system as allelochemicals for the rhizosphere.

ChemInform Abstract: Synthesis and Study of the Antiallergic Activity of 3‐(Chromon‐3‐yl) acrylic Acid Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The Use of Vicinal Twofold Heck Reaction Products in Diastereoselective Sequential Michael Additions — A Convenient Access to Enantiomerically Pure Six‐Ring Anellated Cispentacin Derivatives

AbstractThe palladium‐catalyzed coupling reactions of various acrylic acid derivatives 2a–e (e.g. methyl, tert‐butyl, benzyl, menthyl esters) with 1,2‐dibromobenzene (1), 1,2,3‐tribromobenzene (4) and 1,2‐dibromocyclohexene (6) yielded the correspondingly substituted ortho‐diethenylarenes 3a–e, 1,2,3‐triethenylarenes 5a,b and (E,E)‐1,3,5‐hexatriene derivatives 7a,b. Some of these vicinal diacrylates (3a–d, 5b, 7a,b) were converted to 1,2,3‐trisubstituted indane‐ and tetrahydroindane derivatives 10a–d, 15a,b, 18, 20, 23, and 12a,b, 16b by domino conjugate addition of nitrogen, carbon, and sulfur nucleophiles. With benzyl(trimethylsilyl)amine (9) as an ammonia equivalent, the relative configuration of all three newly formed stereogenic centers was controlled (d.e. >90%). Therefore, with chiral non‐racemic ammonia equivalents like benzyl[(S)‐phenylethyl]amine (14) and TMS‐(R)‐AMP (17), protected diastereomerically pure β‐amino esters were obtained, which could easily be deprotected by standard methods to yield the enantiomerically pure β‐amino acids 27 and 28.

Synthesis of 3-(3-chromonyl)acrylic acid derivatives and their antiallergic activity

Synthesis of 3-(3-chromonyl)acrylic acid derivatives and their antiallergic activity

Michael Additions of 3,3- Dimethylacrylamides and Amines: Synthesis of the Growth Hormone Secretagogue L-692,585

Abstract A highly efficient synthesis of the potent Human Growth Hormone Secretagogue L-692, 585 1 via a Micheal addition with a 3,3-dimethyl acrylic acid derivative 7 and (R)-1-amino-2-propanol 2 is presented.

In vitro and in vivo evaluation of mucoadhesive microspheres prepared for the gastrointestinal tract using polyglycerol esters of fatty acids and a poly(acrylic acid) derivative.

Two types of polyglycerol ester of fatty acid (PGEF)-based microspheres were prepared: Carbopol 934P (CP)-coated microspheres (CPC-microspheres) and CP-dispersion microspheres (CPD-microspheres). Comparative studies on mucoadhesion were done with these microspheres and PGEF-based microspheres without CP (PGEF-microspheres). In an in vitro adhesion test, the CPD-microspheres adhered strongly to mucosa prepared from rat stomach and small intestine because each CP particle in the CPD-microsphere was hydrated and swelled with part of it remaining within the microsphere and part extending to the surface serving to anchor the microsphere to the mucus layer. The gastrointestinal transit patterns after administration of the CPD-microspheres and PGEF-microspheres to fasted rats were fitted to a model in which the microspheres are emptied from the stomach monoexponentially with a lag time and then transit through the small intestine at zero-order. Parameters obtained by curve fitting confirmed that the gastrointestinal transit time of the CPD-microspheres was prolonged compared with that of the PGEF-microspheres. MRT in the gastrointestinal tract was also prolonged after administration of the CPD-microspheres compared with that following the administration of the PGEF-microspheres.

Non‐steroidal Anti‐inflammatory Agents, Part 19: E‐2‐Pyrrolizin‐5‐yl Acrylic Acids as Potent Dual or Selective Inhibitors of Bovine Cyclooxygenase and 5‐Lipoxygenase

The pyrrolizinyl substituted acrylic acid derivatives represent another class of dual and selective inhibitors of cyclooxygenase and 5-lipoxygenase. By modifying their substitution pattern at the phenyl moiety of C-6 the balance between the activity against cyclooxygenase and against 5-lipoxygenase can be shifted. Structure-activity relationships are discussed. Compound 6k is the most potent and well-balanced dual inhibitor of both enzymes, while the highest selectivity of lipoxygenase inhibition was found for 6j. The activity and selectivity of compounds with an additional sulfur moiety depend on the oxidation status of this atom, giving an indication of the discussed coupling between peroxidase and cyclooxygenase. The inhibition of cyclooxygenase was determined in a bovine thrombocyte intact cell assay and that of 5-lipoxygenase using intact bovine PMNLs.

Aminosäuren, 18. Darstellung und Reaktionen von 2‐Isocyanato‐2‐alkensäureestern

Amino Acids, 18. – Preparation and Reactions of 2‐Isocyanato‐2‐alkenoates2‐Isocyanato‐2‐alkenoates 3 were obtained in good yields by the perrhenate‐catalyzed decomposition of 2‐azidoalkanoates 1 in the presence of diphosgene (2a) or phosgene (2b). Methyl 2‐azidopropionate (1h) reacts to give a mixture of methyl 2‐isocyanato‐2‐propenoate (3h) and methyl 2‐chloro‐2‐isocyanatopropionate (4). The addition product 4 could easily be converted into 3h by elimination of HCl with triethylamine at 0°C. With benzyl alcohol (5a) and tert‐butyl alcohol (5b) the isocyanates 3 react smoothly to give the corresponding Z‐ or Boc‐protected 2,3‐didehydroamino acid esters 6 and 7, respectively. The acrylic acid derivative 3h reacts as dienophile with various dienes to yield the Diels‐Alder adducts 8–10.

ChemInform Abstract: A Novel Orally Active Inhibitor of IL‐1 Generation: Synthesis and Structure‐Activity Relationships of 3‐(4‐Hydroxy‐1‐naphthalenyl)‐2‐ propenoic Acid Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Bioadhesive polymers for the peroral delivery of peptide drugs

Two different classes of bioadhesive excipients which have been approved by the FDA, the anionic charged poly (acrylic acid) derivatives and the cationic charged chitosans, have been investigated with respect to their ability to improve intestinal peptide drug absorption. It was found that both polycarbophil and the chitosan derivatives Daichitosan ® VH and chitosan-glutamate (SeaCure ® + 210) enhance the absorption of the peptide drug 9-desglycinamide, 8-arginine vasopressin (DGAVP) in the vertically perfused intestinal loop model of the rat. Recent studies demonstrated that the two poly (acrylates) polycarbophil and Carbopol ® 934P are able to inhibit the activity of the proteolytic enzyme trypsin at pH 6.7, which may lead to an increased stability of the peptide drug in the intestine. The depletion of Ca 2+ out of the incubation medium due to the Ca 2+ binding properties of the poly (acrylates) is discussed as a possible mechanism of action. Because of the observation that depletion of Ca 2+ can additionally cause an opening of tight junctions, the influence of polycarbophil on the paracellular integrity of Caco-2 monolayers was also investigated by measurements of transepithelial electrical resistance (TEER) as well as by visualization studies using confocal laser scanning microscopy. At pH 4.0, apically applied polycarbophil tended to decrease TEER values stronger than the control solution, whereas at pH 7.0 no pronounced changes of TEER could be observed. At pH 7.4, polycarbophil was only able to increase the paracellular permeability of the hydrophilic model compound fluorescein-isothiocyanate-dextran ( M w 4000) when applied to the basolateral side of the Caco2 cell monolayer. In conclusion, bioadhesive polymers are promising absorption promoting agents for peroral delivery of peptide drugs, and their mechanism of action is probably a combination of inhibiting protease activities and modulating the intestinal epithelial permeability.

Synthesis of polyvinylamine and polymer analogous reactions

AbstractPolyvinylamine (PVVAm) was synthesized using the precursor poly(tert‐butyl N‐vinylcarbamate) (PTBNVC). The monomer synthesis was improved, and the control of the molecular weight of the PTBNVC and the PVAm by a transfer reaction with the solvent is demonstrated. TBNVC was radically polymerized. In suspension polymerization molecular weights of 106 g/mol are accessible. Different polymer analogous reactions were carried out. The resulting polymers are methylated polyvinylamine, poly(N‐vinylureas), poly(N‐vinylalkanamides) and PVAm‐adducts with acrylic acid derivatives.

Synthesis of 1‐(4‐substituted)benzyl‐6‐hydroxyisoquinolines with potential activity on NA+,K+‐atpase

AbstractThe synthesis of 1‐(4‐substituted)benzyl‐6‐hydroxyisoquinolines, to be evaluated in the displacement of the specific 3H‐ouabain binding to Na+,K+‐ATPase, is described. The key step involved a cyclization to the isoquinoline ring under Pictet‐Gams conditions which was best performed with the 6‐hydroxy group protected as the benzyl ether. When an unsaturated ester group was present in position 4 of the 1‐benzyl group, this was best introduced before the cyclization step, since the IIeck reaction on 1‐(4‐bromobenzyl)‐6‐hydroxyisoquinoline (8) with acrylic acid derivatives was not successful in all cases.

Decahydroquinoline construction through aza-annulation: A stereoselective synthesis of (±)-5-epipumiliotoxin C.

Aza-annulation of activated acrylic acid derivatives with 3-benzylamino-2-cyclohexenone led to the efficient formation of the corresponding bicyclic lactam. Stereospecific hydrogenation of this unsaturated lactam resulted in the selective formation of the cis fused bicyclic alkaloid, and subsequent elaboration at C-5 and C-2 completed the synthesis of the decahydroquinoline alkaloid (±)-5-epipumiliotoxin C.

One-Pot Preparation of Alcohols from Aromatic Olefins and Acrylic Acid Derivatives by Cobalt(II) Porphyrin-Catalyzed Reductive Oxygenation Followed by Reduction with Trimethyl Phosphite

Abstract Various aromatic olefins and acrylic acid derivatives were converted to benzyl alcohols and α-hydroxyalkanoic acid derivatives in good yields by the reductive oxygenation with oxygen and triethylsilane in the presence of a catalytic amount of cobalt(II) porphyrin followed by treating the reaction mixture with trimethyl phosphite.

Vinylogous Sulfonylureas: A New Class of Acetohydroxyacid Synthase Inhibitors Incorporating a Large Bridging Moiety

Several acrylic acid derivatives incorporating elements of sulfonylurea structure around a central vinylogous core were synthesized and found to be moderate inhibitors of the enzyme, acetohydroxyacid synthase (AHAS). Some com pounds showed post-emergence herbicidal activity against mustard. Biological activity was found to be markedly influenced by the nature of the 2-arylcarbamoyl group. When this group contained a phenyl ring the compounds were inactive. A 4,6-dim ethoxypyrimidin-2-ylcarbamoyl function resulted in the best activity but this activity was highly dependent on the nature of the 4,6-substituents on the pyrimidine ring, with 4,6-dim ethylpyrimidines showing very little activity. The structures of the most active compound, ethyl 3-(2-chlorophenyl)sulfonylamino-3-m ethylthio-2-[(4,6-dimethoxypyrimidin- 2-yl)carbam oyl]acrylate, and an inactive analogue, 4,6-dimethylpyrimidin-2-yl-3-(2-chlorophenyl) sulfonylamino-3-methylthio-2-cyanoacrylate, were determined by X -ray crystallography. The resulting structures showed several conformational differences which may play an important role in inhibitor binding to AHAS and the resultant herbicidal activity.

HETEROCYCLIC SYNTHESIS WITH NITRILES: SYNTHESIS OF SOME NOVEL THIOPHENE AND THIENO[2,3-d]PYRIMIDINE DERIVATIVES

Abstract The thiophene derivative 1 reacts with acrylic acid derivatives 2a-c to give N-alkylated derivatives 3a-c which all undergo further hydrolysis to afford N-(thien-2-yl)-β-alanine derivative 6. While 1 reacts with phenyl isothiocyanate to afford the thiourea derivative 8, it reacts with benzoyl isothiocyanate to afford the dihydrothieno [2,3-d]pyrimidine derivative 9. Compound 1 reacts also with diethyl malonate, thiourea 14a and guanidine 14b to afford the thieno[2,3-d] pyrimidine derivatives 13, 15a and 15b respectively. Benzaldehyde condenses with 1 to give the benzylidene derivative 17 which cyclizes with thioglycollic acid to afford 18.

Heterocyclization reactions of CF 3-substituted 1,1-dicyanoethylenes with nitrogen-containing compounds

The reactions of 1,1-dicyano-2,2-bis(trifluoromethyl)ethylene and esters of 3,3-dicyano-2-(trifluoromethyl)acrylic acid with aryl amines, nitrogen-containing heterocycles and enamines were studied. The possibility of heterocyclic vicinal enaminonitrile formation in these reactions was shown. In certain cases, reactions with the participation of (trifluoromethyl)acrylic acid derivatives lead to lactams. A novel reaction of 1,1-dicyano-2-(trifluoromethyl) ethylenes with aryl amines in the presence of carbonyl compounds leading to the trifluoromethyl substituted derivatives of 1-aryl-l,4-dihydropyridine was investigated.