Wet peroxidation of resorcinol catalyzed by copper impregnated granular activated carbon.

The present article reports the treatment of resorcinol using a catalytic wet peroxidation (CWPO) process in the presence of copper impregnated granular activated carbon (Cu/GAC) with a bench-scale batch reactor. The typical physico-chemical properties of synthesized catalyst were characterized with different equipment and methods. 90% resorcinol removal and 81% of TOC removal was achieved at optimum conditions (pH = 6, the stoichiometric ratio of H2O2/resorcinol = 1.2, catalyst dose = 0.5 g/L, initial concentration of resorcinol = 100 mg/L, temperature = 70 °C and time t = 4 h). Fourier-transform infrared spectroscopy (FTIR) measurements revealed that GAC posses various conjugated hydrocarbon groups including aromatic hydrocarbons, carboxylic groups, carboxyl and carbonate. Cu/GAC catalyst has a surface smoother than that of pristine GAC. At neutral or natural pH (∼6.4) of resorcinol, CWPO of resorcinol is favorable by Cu/GAC catalyst. Catalyst stability study revealed that Cu/GAC sustain its catalytic reactivity to over 76% in the five cycles without any regeneration. The thermogravimetric analysis confirmed that 350 °C temperature found to be optimum for calcination of Cu/GAC without any major losses. The mineralization mechanism was proposed based on intermediates identified during CWPO reaction.

One pot oxidative dehydration - oxidation of polyhydroxyhexanal oxime to polyhydroxy oxohexanenitrile: A versatile methodology for the facile access of azasugar alkaloids.

A unique oxidative dehydration-oxidation of polyhydroxy-oxime (7) to the corresponding ketonitrile (8) in one pot is reported for the first time in carbohydrate literature. Key ketonitrile intermediate (8) upon palladium hydroxide mediated cascade reaction afforded 1-deoxynojirimycin (DNJ) 1b in moderate diastereoselectivity. The cascade reaction involves the conversion of nitrile to amine, heteroannulation, reduction of the imine and subsequent debenzylation to furnish the azasugars. This oxidative dehydration-oxidation and reductive heteroannulation methodology is successfully utilized for the total synthesis of 1-deoxynojirimycin (1b), miglitol (2) and miglustat (3).

An oxidative amidation and heterocyclization approach for the synthesis of ß-carbolines and dihydroeudistomin Y.

A novel synthetic methodology has been developed for the synthesis of dihydro-ß-carboline derivatives employing oxidative amidation-Bischler-Napieralski reaction conditions using tryptamine and 2,2-dibromo-1-phenylethanone as key starting materials. A number of dihydro-ß-carboline derivatives have been synthesized in moderate to good yields using this methodology. Attempts were made towards the conversion of these dihydro-ß-carbolines to naturally occurring eudistomin alkaloids.

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification.

A highly efficient synthesis of enantiomerically pure (S) and (R)-isomers of N-(2,3-dihydroxypropyl)arylamides has been developed with good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral purity was observed.

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters.

A novel synthetic methodology has been developed for the synthesis of diethyl 5-alkyl/aryl/heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates (also called 2-substituted pyrroline-4,5-dihydro-3,3-dicarboxylic acid diethyl esters) by iodide ion induced ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters in very good to excellent yields under mild reaction conditions. The electronic and steric impact of the substituents on the kinetics of ring expansion of N-vinyl aziridines to pyrrolines has been studied. Various diversely substituted novel pyrroline derivatives have been synthesized by this methodology and the products can be used as key intermediates in the synthesis of substituted pyrrolines, pyrroles and pyrrolidines.

The effect of oxime reactivators on muscarinic receptors: functional and binding examinations.

The antidotal treatment of organophosphorus poisoning is still a problematic issue since no versatile antidote has been developed yet. In our study, we focused on an interesting property, which does not relate to the reactivation of inhibited acetylcholinesterase (AChE) of some oximes, but refers to their anti-muscarinic effects which may contribute considerably to their treatment efficacy. One standard reactivator (HI-6) and two new compounds (K027 and K203) have been investigated for their antimuscarinic properties. Anti-muscarinic effects were studies by means of an in vitro stimulated atrium preparation (functional test), the [(3)H]-QNB binding assay and G-protein coupled receptor assay (GPCR, beta-Arrestin Assay). Based on the functional data HI-6 demonstrates the highest anti-muscarinic effect. However, only when comparing [(3)H]-QNB binding results and GPCR data, K203 shows a very promising compound with regard to anti-muscarinic potency. The therapeutic impact of these findings has been discussed.

Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors.

Current treatment of organophosphorus poisoning, resulting in overstimulation and desensitization of muscarinic and nicotinic receptors by acetylcholine (ACh), consists of the administration of atropine and oxime reactivators. However, no versatile oxime reactivator has been developed yet and some mortality still remains after application of standard atropine treatment, probably due to its lack of antinicotinic action. In our study, we focused on the interesting non-acetylcholinesterase property of oximes, i.e. antinicotinic effect of reactivators. Two standard reactivators (HI-6, obidoxime) and two new compounds (K027 and K203) were chosen for in vitro (patch clamp) and in vivo (nerve-evoked muscle contraction) testings. Both examinations showed antinicotinic effects of the reactivators. In vitro inhibition of acetylcholine-evoked currents by obidoxime, HI-6 and K203 was equivalent while K027 was less potent. Similar order of potency was observed by the in vivo examinations. We thus confirm previous in vitro results, which describe antinicotinic effects of oxime reactivators, and furthermore, we show in vivo antagonism of oxime reactivators exerted by the inhibition of ACh effect on the nicotinic receptor in the neuromuscular junction. Taking together, the effects of tested oxime reactivators indicate an antagonism on both embryonic and adult form of the muscle nicotinic receptors.

Interaction of nerve agent antidotes with cholinergic systems.

The poisoning with organophosphorus compounds represents a life threatening danger especially in the time of terroristic menace. No universal antidote has been developed yet and other therapeutic approaches not related to reactivation of acetylcholinesterase are being investigated. This review describes the main features of the cholinergic system, cholinergic receptors, cholinesterases and their inhibitors. It also focuses on the organophosphorus nerve agents, their properties, effects and a large part describes various possibilities in treatments, mainly traditional oxime therapies based on reactivation of AChE. Furthermore, non-cholinesterase coupled antidotal effects of the oximes are thoroughly discussed. These antidotal effects principally include oxime interactions with muscarinic and nicotinic receptors.

A concise formal synthesis of alkaloid cryptotackiene and substituted 6H-indolo[2,3-b]quinolines.

A five-step formal synthesis of alkaloid cryptotackiene and its 2-formyl, 11-methyl/phenyl derivatives involving conjugate addition of enolate anion from cyclohexanone (or 4-methylcyclohexanone) to bis[(methylsulfanyl)methylene]-2-oxindole followed by heterocyclization in the presence of ammonium acetate as the key step has been developed. The 11-methylsulfanyl group in the initial precursor can be either desulfurized (Raney Ni) or replaced by methyl/phenyl groups via nickel-catalyzed cross-coupling reaction with appropriate Grignard reagents.

Reaction of alpha-oxoketene-N,S-arylaminoacetals with Vilsmeier reagents: an efficient route to highly functionalized quinolines and their benzo/hetero-fused analogues.

A simple, highly efficient, and regioselective synthesis of functionalized quinolines through Vilsmeier cyclization of a variety of alpha-oxoketene-N,S-anilinoacetals has been reported. The cyclization is found to be facile with N,S-acetals bearing strongly activating groups on aniline, whereas yields of quinolines are moderate in other cases. The reaction could also be extended for the synthesis of substituted tricyclic benzo[h]quinoline, pyrido[2,3-h]quinoline, 4,7-diphenylphenanthroline, and tetracyclic quino[8,7-h]quinoline by performing a Vilsmeier reaction on N,S-acetals derived from 1-naphthylamine, m-phenylenediamine, o-phenylenediamine, and 1,5-diaminonaphthalene, respectively. A few of the newly synthesized quinolines are subjected to further transformation to afford 2-unsubstituted (Raney-Ni/Ethanol), quinoline-5,8-quinone (NBS/H(2)SO(4)), or 2-alkyl/aryl aminoquinolines through sequential m-CPBA oxidation to the corresponding (2-methylsulfonyl)quinoline followed by replacement with appropriate amines. Similarly, cycloannulation of a few 2-methylthio-3-benzoylquinolines with hydrazine hydrate under microwave irradiation afforded the corresponding substituted and fused pyrazolo[3,4-b]quinolines in excellent yields, whereas TBTH/AIBN-mediated cyclization of the corresponding 3-(2-bromobenzoyl)-2-methylthioquinolines yielded the corresponding benzothiopyrano-fused quinolines through radical translocation.

Domino carbocationic cyclization of functionalized cyclopropyl ketones: facile one-pot access to peri- and angularly fused polycyclic aromatic and heteroaromatic frameworks.

Conjugate adducts obtained by base-induced 1,4-addition-elimination of various aryl/heteroaryl acetonitriles with 1-(2-arylcyclopropyl)-3,3-(bismethylthio)-2-propen-1-ones have been shown to undergo facile acid-induced domino carbocationic rearrangement yielding a variety of substituted tricyclic aromatic and heteroaromatic frameworks in high yields in a one-pot operation. The methodology provides efficient, high-yield routes for synthesis of novel substituted dihydrophenalenes, dihydrobenzo[d,e]anthracene, cyclopenta[a]naphthalene, and fused heteroaromatics such as substituted 4,5-dihydrobenzo[c,d]indole, dihydronaphtho[1,8-b,c]thiophene, dihydroindeno[5,4-b]- and -[4,5-b]-thiophenes, cyclopenta[a]carbazole, and dihydrocyclopenta[e]indazol-3-one derivatives. The probable mechanism of this interesting domino process appears to involve stepwise or concomitant acid-induced ring opening and intramolecular cyclocondensation of cyclopropyl ketones to give benzo-fused arene (or heteroarene) intermediates bearing a reactive benzylic carbocation that is captured intramolecularly either by a preexisting aromatic (or heteroaromatic) ring or by a newly formed benzene ring to give either peri-fused or angularly fused products, respectively. Thus, the overall domino process entails formation of two C-C bonds, a substituted benzene ring along with a peri-fused cyclohexane or angularly fused cyclopentane ring in a single operation.

A new route to spiropyrrolidinyl-oxindole alkaloids via iodide ion induced rearrangement of [(N-aziridinomethylthio)methylene]-2-oxindoles.

A new approach for the synthesis of spiropyrrolidinyloxindole alkaloids, i.e. coerulescine (4) and horsfiline (5) has been developed via iodide ion induced rearrangement of [(N-aziridinomethylthio)methylene]oxindoles 2 to the respective spiropyrroline-2-oxindole derivatives 3 and their subsequent one-pot reductive dethiomethylation-N-methylation. [reaction: see text]

Estimation of gestational age from hand and foot length.

Abortion, foeticide and infanticide have been practised from time immemorial by both primitive and civilized societies. Establishing the precise duration of gestation is an important point in the total medical evidentiary picture of infanticide. In this study, an attempt has been made to establish the gestational age of the foetus using foot and hand length. This study will be of help in establishing the gestational age when the foetus is fragmented. Results obtained were significant in establishing the gestational age.

Mitral valve prolapse syndrome and associated thoracic skeletal abnormalities.

Clinical characteristics of 60 (41 males, 19 females) patients with echocardiographically proven mitral valve prolapse were analysed, with special interest in the associated thoracic skeletal abnormalities. There was a male preponderance (2.2:1) and 91.7% of patients were symptomatic--atypical chest pain, palpitations, exertional dyspnoea and easy fatiguability being the major symptoms. Sixty seven percent had an asthenic body habitus, and 55% had high-arched palate. Thoracic scoliosis (55%), straight back syndrome (50%), flat chest (46.7%), and pectus excavatum (20%) were seen in association with the condition, with 81.7% having any one or combination of these features. Lateral chest radiography showed pancaking of heart shadow in 48.3%. Isolated non-ejection systolic click(s) was the major cardiac auscultatory finding (61.7%), while 60% showed pansystolic prolapse on echocardiography. Electrocardiographic ST-T-U changes in the inferior and/or lateral chest leads were seen in 46.7%, while 16.7% had cardiac arrhythmias. None had infective endocarditis, heart failure or cerebral embolic events. The findings corroborate the view that thoracic skeletal anomalies may be regarded as non-auscultatory features of this syndrome.