Synthesis of new 1H-1,2,4-triazolylcoumarins and their antitumor and anti-HIV activities

A variety of 7-[(1,5-dialkyl-1H-1,2,4-triazolyl)methoxy(and methyl)]coumarins were synthesized from cycloaddition of 2-(2H-benzopyran-7-yloxy)acetonitrile and 2-(5-methoxy-4-methyl-2H-benzopyran-7-yloxy)acetonitrile, respectively, with various reactive cumulene intermediates via spontaneous rearrangements. The anticancer (breast, lung, CNS cancers) and antiviral (HIV-1, HIV-2) properties of some compounds were investigated in vitro. 5-Methoxy-4-methyl-7-[(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-yl)methyl]coumarin showed some inhibition of HIV-1. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 669–678, May, 2006.     

Preparation of 1-Trifluoroethyl-4-methoxy-5-chloropyridazin-6-one: Methyl Shift of 4-Methoxy-5-chloropyridazin-6-one

N1-Trifluoroethyl-4-methoxy-5-chloro-3-pyridazone (4) was synthesized by the substitution reaction of 4methoxy-5-chloro-3-pyridazone (1) with trifluoroethyl trifluoromethanesulfonate (A) at basic condition. In the most of reaction conditions, N1-methyl-4-methoxy-5-chloro-3-pyridazone (2) was obtained as a major by-product, which means that the methyl group in the 4-methoxy shifted to N-1 position inter-molecularly aided by A or trifluoroethyl methanesulfonate (B). We obtained N1-methyl-4-trifluoro-ethoxy-5-chloro-3-pyridazone (3) in the reaction of 1 with B at higher temperature in different solvents with different yield (Table 1 ), which mechanism was shown in Figure 1. When we tried to synthesize 4 in the reaction of 1 with trifluoroethyl toluenesulfonate under basic condition, 6 was obtained (Figure 2). All the detailed mechanisms are undergoing investigated.     

(E)-2-Benzylidenebenzocyclanones: Part X. Determination of log P of (E)-3-benzylidene-2,3-dihydro-1-benzopyran-4-ones by RP-TLC. Effect on log P of Incorporation of Oxygen Atom into Carbocyclic Chalcone Analogues

JPC – Journal of Planar Chromatography – Modern TLC - log P values of 14 biologically active (E)-3-(X-benzylidene)-2,3-dihydro-1-benzopyran-4-ones (3) have been determined by an...     

Erratum on “Probing the kinetics in supramolecular chemistry and molecular assembly by microfluidic-NMR spectroscopy”

Science China Chemistry - In the above referenced publication [1], there is a mistake in the Supporting Information. The corrected caption of Figure S2 is: Figure S2 Isothermal titration...     

Preparation of optically active cyclohexenones: Chirons for the lipophilic moiety of flowery- and woody-like odorant ketones

Optically active 2,5,6,6- and 2,4,4,5-tetraalkylcyclohex-2-en-1-ones ((+)- 2a – d and (?)- 5a – d ), important building blocks for flowery- and woody-like odorants, have been prepared. Compounds (+)- 2a – d and (?)- 5a – d were obtained by ozonolysis of the corresponding cyclopentenic precursors, followed by intramolecular aldol condensation. Alternatively, enones (+)- 2a – d were reduced to the corresponding allylic alcohols ad converted to enones (-)- 5a – d via acidic isomerization and oxidation. ¹³C-NMR assignments are presented.     

O-Methyloximes of Testosterone and of 17α-Methyltestosterone: TLC and QSPR Study of RF Values

JPC – Journal of Planar Chromatography – Modern TLC - The Z (1b and 2b, respectively) and E diastereomers (1c and 2c, respectively) of the O-methyloximes of testosterone (1a) and...     

β-Cleavage of Bis(homoallylic) Potassium Alkoxides. Preparation of 3-Hydroxypropyl and 4-Hydroxybutyl Propenyl Ketones from γ- and δ-Lactones. Synthesis of (±)-Rose oxide

Starting from γ- and δ-lactones 1 – 3 , a two-step preparation of 3-hydroxypropyl and 4- hydroxybutyl propenyl ketones 10 – 18 is described, involving as the key step the β-cleavage of the bis(homoallylic) potassium alkoxides 4a – 9a . The novel methodology is illustrated by a short synthesis of (±)-rose oxide( 20 ).     

1,3-Dipolare Cycloaddition aromatischer Nitril-ylide und Nitril-oxide an Dicyan und Diazocyanide

1,3 Dipolar Cycloaddition of Aromatic Nitrile Ylides and Nitrile Oxides with Cyanogen and Diazocyanides Nitril ylides 2 generated from the imidoyl chlorides 1 react with cyanogen and aryldiazocyanides to 2,5(4)-dia-ryl-1H-imidazole-4(5)-carbonitriles 3a , b or 5(4)-(arylazo)-2,4(5)-diaryl-1H-imidazoles 4a and 2,3,5-triaryl-2,3-dihydro-1H-1,2,4-triazole-1-carbonitriles 5a – f , respectively (Scheme 1). Reactions of benzonitrile oxides 7 with these dipolarophiles lead to 3,3′-diaryl-5,5′-bi[1,2,4]oxadiazoles 8a – c or 3-aryl-5-(arylazo)-1,2,4-oxadiazoles 9a – j (Scheme 2).     

Standardization and validation of a high-performance thin-layer chromatography method for the quantification of aflatoxin B1 and its application in surveillance of contamination level in marketed food commodities from the Mumbai region

JPC – Journal of Planar Chromatography – Modern TLC - Aflatoxin B1 (AFB1) is a natural carcinogenic contaminant of agricultural product regulated at parts per billion (ppb) level;...     

HPTLC Detection and Identification of Heroin (Diacetylmorphine) in Forensic Samples. Part III

JPC – Journal of Planar Chromatography – Modern TLC - Anew spray reagent, a 1% (w/v) aqueous solution of ferric chloride and a 1% (w/v) acidified alcoholic solution of...     

Methyl and Phenylmethyl 2-Acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate in the Synthesis of heterocyclic systems: Preparation of 3-amino-4H-pyrido-[1,2-a]pyrimidin-4-ones

Methyl 2-acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate ( 4 ) and phenyl-methyl 2-acetyl-3-{[2-(dimethylamino)-1(methoxycarbonyl)ethenyl]amino}prop-2-enoate ( 5 ) were prepared in three steps from the corresponding acetoacetic esters, and used as reagents for the preparation of N³-protected 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 10 – 12 , 5H-thiazolo[3,2-a]pyrimidin-5-one 13 , 4H-pyrido[1,2-a]-pyridin-4-one 19 and 2H-1-benzopyran-2-ones 20 – 23 . Free 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 24 – 26 were prepared from 10 – 12 by removal of the 2-(methoxycarbonyl)-3-oxobut-1-enyl or 3-oxo-2-[(phenyl-methoxy)carbonyl]but-1-envl as N-protecting group by various methods.     

Polymerization of Styrene by Thermal Scission of C-C Bond

A radical induced polymerization of syrene (St) with diethyl-2, 3-dicyano-2,3-diphenylsuccinate (1), producing ultra high molecular polystyrene wasreported herein. The polymerizations of syrene with dl-1 at 70-90℃ are shown in Figure 1. In this case, M of polymers was observer to in crease with reaction time.     

Theoretical study on chlorine and hydrogen shift in cycloheptatriene and cyclopentadiene derivatives

The transition structures (TSs) for chlorine 1,7-shift and 1,5-shift in 1,7,7-trichlorocycloheptatriene (1) and those of chlorine 1,5-shifts in 1,5,5-trichlorocyclopentadiene (3) and 1,2,5-trichloro-1,3-pentadiene (5) derivatives have been located with density functional theory (DFT) at the Becke3LYP/6-311G [and Becke3LYP/6-311+G] level. The calculational results were compared with those for corresponding hydrogen shifts in nonsubstituted molecules (cycloheptatriene (2), cyclopentadiene (4), and 1,3-pentadiene (6)). The following points were clarified: (1) The activation energy (Delta E(++)) for chlorine 1,7-shift in 1 was evaluated to be only +50.1 [+49.2] kJ/mol, which is smaller than that (+69.9 [+68.3]) for a 1,5-shift, supporting the theory that the conversion between two equivalent A and A' proceeds through a TS for direct chlorine 1,7-shift (Figure 1), rather than through a TS for a 1,5-shift (Figure 2). (2) The considerable amount of charge separation between a migrating chlorine atom (Cl(m)) and a seven-membered ring (-0.53 and +0.47 for Merz-Singh-Kollman scheme) occurs in a chlorine 1,7-shift, which is in good contrast to the result that the migrating hydrogen atom (H(m)) for a 1,7-shift in cycloheptatriene (2) carries almost no charge (Figure 3). This large charge separation can stabilize the TS for the chlorine 1,7-shift pathway. (3) The Delta E(++) values for suprafacial hydrogen 1,7-shift in 2 are quite large (+288.0 [+284.8] kJ/mol), much larger than that (+166.8 [+167.0]) for a 1,5-shift in 4 which is orbital symmetrically allowed (Figure 3). The calculation suggests that the chlorine 1,7-shift in 1 occurs easily at room temperature (actually observed experimentally) by proceeding via concerted suprafacial 1,7-shift through the zwitterionic TS with the significant assistance of Coulomb interaction between charged fragments (negatively charged chlorine atom and positively charged tropylium ring), rather than via a suprafacial 1,5-sigmatropic pathway. Other cases studied in this paper showed usual results predicted by orbital symmetrical consideration.     

Synthesis and Complexation Properties of a New Class of Receptors based on a cone-configurated tetra-p-(tert-butyl)calix[4]arene and bipyridyl subunits

0The bipyridyl-armed tetra-p-(tert-butyl)calix[4]arenes 1 – 5 were synthesized from tetra-p-(tert-butyl)-calix[4]arene A and 6-(bromomethyl)-6′-methyl-2,2′-bipyridine ( B ) by direct base-strength-driven regioselective O-alkylation or by stepwise procedures. Preliminary complexation studies of the ligands 1 – 3 with Cu^I affording the complexes 6 – 8 are described.     

Electron ionization mass spectra of novel 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose derivatives and related sugar sulfamates

The electron-impact (EI) mass spectral fragmentation of ten bis-O- (1-methylethylidene)fructopyranose derivatives and three related sugar sulfamates were investigated. In particular, 2,3:4,5-bis-O - (1-methylethylidene)-β-D-fructopyranose sulfamate (topiramate), a potent anticonvulsant, was examined in greater detail. The fragmentation of the 2,3:4,5-bis-O-(1-methylethylidene) fructopyranose derivatives in general was not very dependent on the nature of substitution; the mechanisms of the common and unique fragmentation patterns are presented. These compounds showed characteristic peaks at m/z [M – 15]⁺, [M – 15 – 58]⁺, [M – 15 – 58 – 60]⁺, [M ? CH₂X]⁺ and [M ? CH₂X – 58]⁺ where X = OSO₂NR₂ (R ? H, CH₃, and/or Ph), OC (O)NHR, NH₂, CI and OH. The fragmentation of isomeric bis-O-(1-methylethylidene) derivatives of aldopyranose, ketopyranose and ketofuranose sulfamates was also investigated. The results indicate that isomeric sugar sulfamates can be easily distinguished in the EI mode. Key fragmentation pathways are discussed for these compounds.     

Synthesis of abasic locked nucleic acid and two seco-LNA derivatives and evaluation of their hybridization properties compared with their more flexible DNA counterparts

To investigate the structural basis of the unique hybridization properties of LNA (locked nucleic acid) three novel LNA derivatives with modified carbohydrate parts were synthesized and evaluated with respect to duplex stabilities. The abasic LNA monomer (X(L), Figure 1) with the rigid carbohydrate moiety of LNA but no nucleobase attached showed no enhanced duplex stabilities compared to its more flexible abasic DNA counterpart (X, Figure 1). These results suggest that the exceptional hybridization properties of LNA primarily originate from improved intrastrand nucleobase stacking and not backbone preorganization. Two monocyclic seco-LNA derivatives, obtained by cleavage of the C1'-O4' bond of an LNA monomer or complete removal of the O4'-furanose oxygen atom (Z(L) and dZ(L), respectively, Figure 1), were compared to their acyclic DNA counterpart (Z, Figure 1). Even though they are more constrained than Z, the seco-LNA derivatives Z(L) and dZ(L) destabilize duplex formation even more than the flexible seco-DNA monomer Z.     

Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling

Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M – 2H]^2– ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M – 3H]^3– ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M – 2H]^2– ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M – 3H]^3– ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented.

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Influence of the Regression Technique on the Extrapolated Retention Values of Single-Point Adsorption Compounds on Silica Gel

JPC – Journal of Planar Chromatography – Modern TLC - The retention (RM) values of nine one-point adsorption model compounds: diphenylamine, indol, 2-naphtol, 1-naphtol, 1-naphtylamine,...     

Conductivity of Al2(WO4)3–WO3 and Al2(WO4)3–Al2O3 Composites

Russian Journal of Electrochemistry - Composites of (1 – x)Al2(WO4)3–xWO3 and (1 – x)Al2(WO4)3–xAl2O3 are synthesized and their conductivity is studied as dependent on the...     

Identification of Coexisting Pentose,Hexose, and Disaccharides with Preliminary Separation through Hydrophilic Interaction on Silica HPTLC Plate Using Aqueous Sodium Deoxycholate-Acetonitrile Mobile Phase System

JPC – Journal of Planar Chromatography – Modern TLC - Aqueous micellar bile salt, sodium deoxycholate (NaDC) solution as additive in acetonitrile (ACN) in the ratio (1:5 v/v) was...