Novel routes for the generation of structurally diverse labdane diterpenes from andrographolide

Andrographolide 1, the major constituent of the Indian medicinal plant Andrographis paniculata (Acanthaceae) was converted into the key intermediate 4 by selective oxidative degradation of the C-12,13 olefin bond. The aldehyde functional group present in 4 has been utilized for synthesizing a number of structurally diverse labdane diterpenes. Synthesis and in vitro cytotoxic activity results of the compounds prepared are discussed.     

Development and Validation of a GC–MS Method for the Determination of Methyl and Ethyl Camphorsulfonates in Esomeprazole Magnesium

A rapid gas chromatography–mass spectrometry method for the identification and determination of two carcinogenic impurities viz. methyl camphorsulfonate (MCS) and ethyl camphorsulfonate (ECS) in esomeprazole magnesium (EOM) is developed for the first time. The factors affecting method development and the fragmentation patterns of MCS and ECS based on the mass spectral analysis are described. The limit of detection and limit of quantitation values for both compounds were established as 3 and 10 ppm, respectively with respect to 50 mg mL^?1 of EOM. The method is linear within the range of 10–120 ppm and found to be precise, accurate, specific and robust.     

Structure and dynamic response of radiative diffusion flames

Nitrogen-diluted hydrogen burning in air is modeled numerically using a constant density and one-step reaction model in a plane two-dimensional counterflow configuration. An optically thin assumption is used to investigate the effects of radiation on the dynamics, structure, and extinction of diffusion flames. While there exist dual steady-state extinction limits for the 1D radiative flame response, it is found that as the 1D radiative extinction point is approached the 1D low-stretch diffusion flame exhibits oscillatory response, even with sub-unity Lewis number fuel. These radiation-induced limit cycle oscillations are found to have increasing amplitude and decreasing frequency as the stretch rate is reduced. Flame oscillation eventually leads to permanent extinction at the stretch rate which is larger than the steady-state radiative extinction value. Along the 1D radiative response curve, the transition from 1D flame to 2D structure and the differences in the resulting 2D flame patterns are also examined using a variety of initial profiles, with special emphasis on the comparison of using the initial profiles with and without a flame edge. Similar to the previous studies on the high-stretch adiabatic edge flames using the same configuration, the high-stretch radiative flames are found to resist 1D blow-off quenching through various 2D structures, including propagating front and steady cellular flames for initial profiles with and without flame edges. For all initial profiles studied, the low-stretch radiative flames are also found to exhibit different 2D flame phenomena near the 1D radiative extinction limit, such as transient cellular structures, steady cellular structures, and pulsating ignition fronts. Although the results demonstrate the presence of low-stretch and high-stretch 2D bifurcation branches close to the corresponding 1D extinction limits irrespective of the initial profile used, particular 2D flame structures in certain stretch rate range are initial profile dependent. The existence of two-dimensional flame structures beyond the 1D steady-state radiative extinction limit suggests that the flammable range is expanded as compared to that predicted by the 1D model. Hence, multi-dimensional flame patterns need to be accounted for when determining the flammability limits for a given system.     

Dithiocarbamate and CuO promoted one-pot synthesis of 2-(N-substituted)-aminobenzimidazoles and related heterocycles

A rapid and efficient one-pot method for the synthesis of 2-(N-substituted)-aminobenzimidazoles is described. The reaction is promoted by dithiocarbamate and catalytic CuO. This procedure is general and can be applied to synthesize many potential drug candidates.     

Development and validation of stability-indicating HPLC and UPLC methods for the determination of bicalutamide

Six new process related impurities (Imp-08, Imp-09, Imp-10, Imp-12, Imp-13 and Imp-14) of bicalutamide (BCT) have been reported in this paper. BCT was subjected to oxidative, acid, alkaline, hydrolytic, thermal and photolytic degradation conditions and found to degrade in alkaline condition, yielding Imp-11. Stability-indicating high-performance liquid chromatography and ultra-performance liquid chromatography methods were developed for the determination of BCT in the presence of its 14 process-related impurities and 1 degradant by using Zorbax SB phenyl column (150 × 4.6 mm × 3.5 μm) and HSS T3 column (100 × 2.1 mm × 1.8 μm), respectively. Both the methods were validated as per International Conference on Harmonization guidelines. Quantitation limits (QL) were found be in the ranges of 0.02-0.03% for both the methods. Precision was evaluated by replicate analysis in which % relative standard deviation (RSD) values for areas were found below 2.0. Linearity for the impurities was established in the range of QL to 200% of the specification level and the correlation coefficients derived from of the respective calibration curves were approximately 0.999. The recoveries obtained for purity (90-100%) and assay (98-102%) ensured the accuracy of the developed methods.     

Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes

Microwave-promoted synthesis of 2-aminothiophenes by multicomponent reactions of a ketone with an active nitrile and elemental sulfur under KF-alumina catalysis is described.     

Development and validation of LC methods with visible detection using pre-column derivatization and mass detection for the assay of voglibose

Two sensitive and selective liquid chromatographic methods were developed for the assay of voglibose (VB) and validated as per International Conference on Harmonization (ICH) guidelines. First method is based on the pre-column derivatization of VB followed by visible detection (LC-VD) and second method involves mass spectrometric detection (LC-MS). In LC-VD method, VB was derivatized with sodium metaperiodate and 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH). The derivatized color product of VB (DCPVB) was run through Novapak C18 (300 × 3.9 mm, 4 μm) column using the mobile phase containing buffer (0.01 M mixture of sodium di hydrogen orthophosphate and disodium hydrogen orthophosphate, pH 6.0) and acetonitrile in 35:65 v/v ratio. The eluted DCPVB was monitored at 667 nm. The fixation of optimum conditions in LC-VD method is described. DCPVB structure was confirmed by mass spectral analysis. In LC-MS method, VB was passed through Venusil XBPPH (150 × 4.6 mm, 5 μm) column using a 95:5 v/v mixture of 0.01% formic acid and methanol as mobile phase. The assay concentrations of VB in pure form and in tablets for LC-VD and LC-MS methods are 25 and 5 ng ml⁻¹, respectively.     

Studies toward the total synthesis of tedanolide: stereoselective synthesis of the C(8)-C(17) segment

The stereoselective synthesis of the C(8)-C(17) sub-unit (−)-5 of tedanolide (1), which involves iterative Evans aldol reactions as the key steps, is described.     

Co(III), Rh(III) & Ir(III)-Catalyzed Direct C−H Alkylation/Alkenylation/Arylation with Carbene Precursors

Metal carbenes play a pivotal role in transition-metal-catalyzed synthetic transfer reactions. The metal carbene is generated either from a diazo compound through facile extrusion of N₂ with a metal catalyst or in situ generated from other sources like triazoles, pyriodotriazoles, sulfoxonium ylides and iodonium-ylide. On the other hand, Co(III), Rh(III) & Ir(III)-catalyzed C−H functionalizations have been well established as a key synthetic step to enable the construction of various synthetic transformations. Interestingly, in recent years, merging of these two concepts C−H activation and carbene migratory insertion gained much attention, in particular group 9 metal-catalyzed arene C−H functionalizations with carbene precursors via carbene migratory insertion. In this review, we summarize recent advances in Co(III), Rh(III) & Ir(III)-catalyzed direct C−H alkylation/alkenylation/arylation with carbene precursors and also discuss key synthetic intermediates within the catalytic cycles.     

On bigraded regularities of Rees algebra

For any homogeneous ideal I in \(K[x_1,\ldots ,x_n]\) of analytic spread \(\ell \), we show that for the Rees algebra R(I), \({\text {reg}}_{(0,1)}^{\mathrm{syz}}(R(I))={\text {reg}}_{(0,1)}^{\mathrm{T}}(R(I))\). We compute a formula for the (0, 1)-regularity of R(I), which is a bigraded analog of Theorem 1.1 of Aramova and Herzog (Am. J. Math. 122(4) (2000) 689–719) and Theorem 2.2 of Römer (Ill. J. Math. 45(4) (2001) 1361–1376) to R(I). We show that if the defect sequence, \(e_k:= {\text {reg}}(I^k)-k\rho (I)\), is weakly increasing for \(k \ge {\text {reg}}^{\mathrm{syz}}_{(0,1)}(R(I))\), then \({\text {reg}}(I^j)=j\rho (I)+e\) for \(j \ge {\text {reg}}^{\mathrm{syz}}_{(0,1)}(R(I))+\ell \), where \(\ell ={\text {min}}\{\mu (J)~|~ J\subseteq I \text{ a } \text{ graded } \text{ minimal } \text{ reduction } \text{ of } I\}\). This is an improvement of Corollary 5.9(i) of [16].