Insulin Secretagogues from Moringa oleifera with Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Activities

Bioassay‐directed isolation and purification of the methanol extract of Moringa oleifera fruits yielded bioactive N‐benzyl thiocarbamates, N‐benzyl carbamates, benzyl nitriles, and a benzyl ester. Among these, methyl 2‐[4‐(α‐L ‐rhamnopyranosyl)phenyl]acetate ( 2 ), N‐[4‐(β‐L ‐rhamnopyranosyl)benzyl]‐1‐O‐α‐D ‐glucopyranosylthiocarboxamide ( 3 ), 1‐O‐phenyl‐α‐L ‐rhamnopyranoside ( 5 ), and 4‐[(β‐D ‐glucopyranosyl)‐(1→3)‐(α‐L ‐rhamnopyranosyl)]phenylacetonitrile ( 6 ) are novel, and their structures were determined by spectroscopic methods. The known compounds isolated and characterized from the MeOH extract were niazirin (=4‐(α‐L ‐rhamnopyranosyl)phenylacetonitrile; 1 ), niazicin A (=methyl N‐{4‐[(4′‐O‐acetyl‐α‐L ‐rhamnopyranosyl)benzyl]}thiocarbamate; 4 ), methyl N‐{4‐[(α‐L ‐rhamnopyranosyl)benzyl]}carbamate ( 7 ), and methyl N‐{4‐[(4′‐O‐acetyl‐α‐L ‐rhamnopyranosyl)benzyl]}carbamate ( 8 ). The combined yield of these compounds from dried M. oleifera fruits was 1.63%. In rodent pancreatic β‐cells (INS‐1), compounds 4, 5, 6, 7 , and 8 at 100 ppm significantly stimulated insulin release. Cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) enzyme inhibition assays revealed that 5 and 6 were most active at 83 ppm. Compound 6 , however, demonstrated greater specificity for inhibition of COX‐2 enzyme (46%) than COX‐1 enzyme. Lipid peroxidation assays revealed that 4 and 6 at 50 ppm inhibited peroxidation reactions by 80 and 95%, respectively, while 3 and 8 inhibited lipid peroxidation by 35%. These compounds did not inhibit the cell growth when tested with human breast (MCF‐7), central nervous system (CNS, SF‐268), lung (NCI‐H460), or colon (HCT‐116) cancer cell lines. Moreover, these compounds were not cytotoxic at the concentrations tested.     

Two unprecedented multicomponent reactions involving N-heterocyclic carbenes, activated acetylenes, and aldehydes

[reaction: see text] Two unprecedented multicomponent reactions of N-heterocyclic carbenes involving activated acetylenes and aldehydes are described.     

Thermal Decomposition Kinetics of Lanthanum Complexes of 1,2-(Diimino-4'-Antipyrinyl)ethane

The kinetics and mechanism of the thermal decomposition of perchlorate, nitrate and iodide complexes of lanthanum with the Schiff base 1,2-(diimino-4'-antipyrinyl)ethane (abbreviated as GA) have been studied by TG and DTG techniques. The kinetic parameters like the activation energy, the pre-exponential factor and the entropy of activation were calculated for the major decomposition stages (Stages I and II) using Coats-Redfern equation. The rate controlling process obey ‘Mampel model’ with random nucleation with one nucleus on each particle. The kinetic parameters indicate that the ligands are loosely bound to metal ion and the activated complex formed in the decomposition reaction is more ordered than the reactants. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular dynamics implementation in MSINDO: study of silicon clusters

Born-Oppenheimer molecular dynamics is implemented in the semiempirical self-consistent field molecular orbital method MSINDO. The method is employed for the investigation of the structure and dynamics of silicon clusters of various sizes. The reliability of the present parameterization for silicon compounds is demonstrated by a comparison of the results of simulated annealing and of density functional calculations of Si(n) clusters (n = 5-7). The melting behavior of the Si(7) cluster is investigated and the MSINDO results are compared to previous high-level calculations. The efficiency of the present approach for the treatment of large systems is demonstrated by an extensive simulated annealing study of the Si(45) and Si(60) clusters. New Si(45) and Si(60) structures are found and evaluated. The relative stability of various energy minimum structures is compared with density functional calculations and available literature data.     

An Exceptional Set in the Ergodic Theory of Markov Maps of the Interval

It is known that a Markov map T of the unit interval preservesa measure µ, say, equivalent to Lebesgue measure, andthat almost every point of the interval has a forward orbitunder T that is uniformly distributed with respect to µ.In the opposite direction the main result of this paper statesthat there is a set of points having Hausdorff dimension 1 whoseforward orbits are in a certain sense very far from being sodistributed. 1991 Mathematics Subject Classification: 58F08,28A80.     

Total synthesis of cryptophycin-24 (Arenastatin A) amenable to structural modifications in the C16 side chain

Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).     

Uncatalyzed chemical oscillations in the aqueous acidic bromate oxidation of veratraldehyde

Oscillatory behavior in the uncatalyzed aqueous acidic bromate oxidation of 3,4-dimethoxybenzaldehyde (veratraldehyde) is reported. The generally used H₂SO₄ can be substituted by HNO₃, HClO₄, CCl₃ COOH and H₃PO₄ in this system. The length of the induction period is found to be dependent on the initial concentrations of the reagents and this effect is more prominent in the case of acidity. The precipitate accumulated in the reaction during oscillations has been identified. A plausible mechanism is also suggested. Experiments with allyl alcohol, a bromine scavenger, suggest that elemental bromine formed in the reaction has a role in the mechanism together with or besides bromide inons.

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3,4- () . H₂SO₄ HNO₃, HClO₄, CCl₃ COOH H₃PO₄ . . , , . . , , , , , .

     

Oscillatory behavior in the oxidation of hematoxylin with bromate and sulfuric acid

Uncatalyzed and catalyzed oscillatory behavior in the redox potential in the oxidation of hematoxylin with acidic (H₂SO₄) bromate is reported.

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- (H₂SO₄) .

     

Analogues of the Quararibea metabolite chiral enolic-γ-lactone from (2S,3S)- and (2S,3R)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acids

Reaction of dialkyl (2S,3S)- or (2S,3R)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylates with POCl₃ in pyridine followed by diazomethane resulted in the isolation of dialkyl 2S-4-methoxy-5-oxo-2,5-dihydro-2,3-furandicarboxylates, which are analogues of the Quararibea metabolite chiral enolic-γ-lactone (3-hydroxy-4,5-(R)-dimethyl-2(5H)-furanone). An unusual α-hydroxylation of γ-butyrolactone takes place involving POCl₃ in pyridine. When the dehydration was facilitated with methanesulfonyl chloride in triethylamine, instead of POCl₃, aromatic dialkyl 5-[(methylsulfonyl)oxy]-2,3-furandicarboxylates were obtained.