Enantiomeric separation of novel anticancer agent 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one

The enantiomers of 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one, a novel anticancer agent, were separated by derivatisation with caronaldehyde, separation of the resulting diastereoisomers of the corresponding esters by silica gel column chromatography and regeneration of alcohols (S)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one under aqueous conditions. The absolute configuration of the enantiomers was determined by 1H NMR studies of the corresponding Mosher esters. Alternatively, the enantiomers were separated by preparative HPLC to collect the (S)- and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-ones with high purity which was comparable with that obtained by the chemical method. The details of these methods have been presented herein.     

Synthesis of tetrahydro-5-azaindoles and 5-azaindoles using Pictet-Spengler reaction—appreciable difference in products using different acid catalysts

Pictet-Spengler condensation of 2-(aryl)-2-(1H-pyrrol-2-yl)ethanamines using conventional acid catalysts like TMSCl or TFA resulted in the formation of substituted 5-azaindoles involving a tandem one pot four steps reaction sequence. By contrast use of glacial acetic acid furnished the targeted tetrahydro-5-azaindoles in diastereoselective manner. These were readily dehydrogenated to 5-azaindoles.     

A novel catalyst-free,eco-friendly,on water protocol for the synthesis of 2,3-dihydro-1H-perimidines

The first greenest methodology for the synthesis of 2,3-dihydro-1H-perimidines on water is described. 1,8-Diamino naphthalene was reacted with different types of aldehydes at room temperature to furnish the product in moderate to excellent yields in 30 min. A multi-gram scale reaction is also performed to ensure the scalability of the reaction.     

Mechanism of oxidation of DL-methionine by iron(III)-2,2′-bipyridyl in perchloric acid—a kinetic study

Summary The kinetics of oxidation of DL-methionine by iron(III)-2,2-bipyridyl complex in HClO₄ were studied using 20%(v/v) MeOH as solvent. The order with respect to methionine and iron(III) was unity. The rate increased with increased [bipyridyl], but decreased with increased [H⁺]. While the reactive species of the substrate was the zwitterionic form, that of the oxidant was [Fe(bipy)₂-(H₂O)₂]³⁺. At 55 °C E _a and S for the reaction were 50.6 ± 2.5 kJ mol^–1 and –111.4 ± 7.6 JK^–1 mol^–1, respectively.Author to whom all correspondence should be directed.     

Efficient one-pot synthesis of anti HIV and antitumor compounds: harman and substituted harmans

Anti HIV and antitumor compounds, harman and substituted harmans have been synthesized using electrocyclization reactions as key steps. A one-pot reaction sequence was used to furnish these compounds in good overall yield.     

De novo design of strand-swapped beta-hairpin hydrogels

De novo designed peptides, capable of undergoing a thermally triggered beta-strand-swapped self-assembly event leading to hydrogel formation were prepared. Strand-swapping peptide 1 (SSP1) incorporates an exchangeable beta-strand domain composed of eight residues appended to a nonexchangeable beta-hairpin domain. CD shows that, at pH 9 and temperatures less than 35 degrees C, this peptide adopts a random coil conformation, rendering it soluble in aqueous solution. On heating to 37 degrees C or greater, SSP1 adopts a beta-hairpin that displays an exchangeable beta-strand region. The exchangeable strand domain participates in swapping with the exchangeable domain of another peptide, affording a strand-swapped dimer. These dimers further assemble into fibrils that define the hydrogel. A second peptide (SSP2) containing an exchangeable strand composed of only four residues was also studied. Microscopy and scattering data show that the length of the exchangeable domain directly influences the fibril nanostructure and can be used as a design element to construct either twisted (SSP1) or nontwisted (SSP2) fibril morphologies. CD, FTIR, and WAXS confirm that both peptides adopt beta-sheet secondary structure when assembled into fibrils. Fibril dimensions, as measured by TEM, AFM, and SANS indicate a fibril diameter of 6.4 nm, a height of 6.0 nm, and a pitch of 50.4 nm for the twisted SSP1 fibrils. The nontwisted SSP2 fibrils are 6.2 nm in diameter and 2.5 nm in height. Oscillatory rheology, used to measure bulk hydrogel rigidity, showed that the gel composed of the nontwisted fibrils is more mechanically rigid (517 Pa at 6 rad/s) than the gel composed of twisted fibrils (367 Pa at 6 rad/s). This work demonstrates that beta-strand-swapping can be used to fabricate biomaterials with tunable fibril nanostructure and bulk hydrogel rheological properties.     

Oxidative DNA damage following photoexcitation of daunomycin: Direct role of oxygen

The chemistry of the photoactivation of daunomycin–DNA complexes is reported and the mechanism is elucidated. We quantitatively assessed the type of DNA damage, such as strand breaks, oxidized bases, and abasic sites, that arise using a plasmid relaxation assay coupled with DNA repair endonucleases. Photoexcitation of daunomycin leads to oxidative DNA damage in a dose- and irradiation time-dependent manner and guanine-specific oxidized purines are substantially produced under these conditions. Oxidative DNA base damage was also inhibited by argon degassing, indicating that guanine-specific damage arises from an oxygen-dependent mechanism. In addition, photoexcitation of daunomycin–DNA complexes leads to superoxide anion radical formation. From these studies of the actual product formed, we conclude that a charge transfer is a main driving force of the mechanism.     

Density functional approach to thermodynamics of self-assembly

A local density functional approximation for predicting the surface crystallization of a thermodynamically small system under gravity is described and tested. Using the model of the classical soft-sphere fluid, the state parameters for such systems are identified. A generalized phase diagram based upon the scaling variables is obtained; systems with the same reduced-state parameters exhibit identical profiles of thermodynamic properties such as density, pressure, and intrinsic chemical potential, measured in the direction of the applied field. The point-thermodynamic approximation of Rowlinson and the local density approximation of the density functional formalism are found to be remarkably accurate. A configurational temperature is defined and shown to agree with the corresponding kinetic temperature for inhomogeneous systems at equilibrium. The structural profiles at the crystal-fluid interface are indicative of a mesolayer of lower density crystal, not seen in the field-free isobaric crystal-liquid interface.