Nazira Karodia

Phosphonium tosylates as solvents for the Diels-Alder reaction.

Abstract Phosphonium tosylates have been investigated as solvents for the Diels–Alder reactions of isoprene with methyl acrylate, but-3-en-2-one and acrylonitrile. The reactions with oxygen-containing dienophiles showed high regioselectivity.

Clean catalysis with ionic solvents—phosphonium tosylates for hydroformylation

High-melting phosphonium tosylates are synthesised and applied for the first time as solvents in catalytic hydroformylation reactions; variation in the substituents attached to phosphorus can lead to markedly different results; the catalyst systems are non-corrosive, easily manipulated and can readily be recovered and reused.

Development of selective DprE1 inhibitors: Design, synthesis, crystal structure and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides

Decaprenylphosphoryl-b-D-ribose 20-epimerase (DprE1) is a potential drug target for development of antitubercular agents. Structure based drug discovery approach yielded twenty novel derivatives of benzothiazolylpyrimidine-5-carboxamides (7a-t) which were synthesised by three component one pot reaction involving benzothiazolyl oxobutanamide, thiourea and substituted aromatic benzaldehydes. These derivatives were evaluated for antitubercular activity to determine MIC and compound 7a, 7e, 7f and 7o were found to be potentially active against Mycobacterium tuberculosis (H37Rv). Log P of these compounds was found to be between 2.0 and 3.0 making them suitable for oral dosing. DprE1 selectivity and pharmacokinetic studies were carried out for these compounds of which 7a and 7o were found to be highly selective and bioavailability was found to be above 52% by oral dose. Crystal structure of 7a was studied and molecular packing was determined, it exhibited a triclinic crystal lattice arrangement having hydrogen bonded dimeric arrangement. Drug receptor interactions were studied which exhibited docking in the active site of receptor with hydrogen bonding, hydrophobic interactions, vdW interactions with amino acid residues such as Cys387, Asn385, Lys418, Tyr314, Gln334 and Lys367 respectively. 3D QSAR analysis was carried out by kNN-MFA method to determine and develop theoretical model, best suitable model was found to be based on Simulated Annealing k-Neariest Neighbour Molecular Field Analysis (SA kNN-MFA). The model provided with hydrophobic descriptors in positive side indicating the need of bulky groups, steric and electronegative descriptors in negative coordinates hints with contribution by the electronegative substitutions as favourable and desirable moieties for enhancing the activity. The q(2), q(2)_se and Pred_r(2)se were found to be 0.5000, 0.6404 and 1.0094 respectively. A pharmacophore model was generated which suggested for necessity of aromatic, aliphatic carbon centre and hydrogen bond donor for development of newer DprE1 selective inhibitors.

Clean catalysis with clean solvents – phosphonium tosylates for transfer hydrogenation reactions

Molten salts have been applied for the first time as solvents in rhodium‐catalysed transfer hydrogenation reactions. The salts are tetraalkyl/aryl phosphonium tosylates; they are liquid at the reaction temperature and solid at room temperature, thereby facilitating catalyst recovery. In certain cases they can give rise to favourable enantioselectivities.

Facile Synthesis of Benzotriazines and Indoles by Ring-Scissions of α-Benzotriazol-1-yl Hydrazones

Abstract: α-(Benzotriazol-1-yl)hydrazones 2a-d and 13a-c were prepared by refluxing the corresponding α-(benzotriazol-1-yl)ketones with p-tosyl hydrazide or benzenesulfonyl hydrazide. Treatment of 2a-b with n-butyllithium in the presence of TMEDA gave benzotriazines 6a-b, while lithiation of 13a-c resulted in indole derivatives 16a-c, depending on the structure of the hydrazones.

Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 5. Selective extrusion of PH3PO from β,γ,β′-trioxo ylides to give diacylalkynes

Sixteen examples of the previously unknown trioxo ylides 7 have been prepared by acylation of stabilised phosphorus ylides 8 with α-oxo acid chlorides 9. Extrusion of Ph3PO from these is readily achieved using FVP at 500 °C in most cases, to afford the diacylalkynes 10 in moderate yield. Three examples failed to give the expected alkynes and the nature of the processes involved in these cases is uncertain. Fully assigned 13C NMR spectra are presented for the ylides and an unexpected pattern is observed in the value of JP–C for the three carbonyl carbons depending on the nature of the substituents present. There is some correlation between the value of 2JP–C for the central carbonyl carbon and the success of the pyrolysis although this is not complete. The method has been used to prepare a specifically 13C labelled acetylenic diester 14.

Synthesis and Evaluation of Selected Benzimidazole Derivatives as Potential Antimicrobial Agents.

A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.

Preparation and catalytic properties of resin bound binuclear rhodium tetracarboxylate complexes

-(4′-Polystyrylmethyloxy)-3-carboxylatomethyloxy-1-phenylacetate bis-μ-coordinated rhodium(II) diacetate complex, a resin-bound analogue of dirhodium tetraacetate in which two adjacent μ-bridging acetate moieties are covalently linked, serves as an efficient, stable and re-useable immobilised alkene hydrofomylation and hydrogenation catalyst. 4-(4′-Polystyrylmethyloxy)-3-carboxylatomethyloxy-1-phenylacetate bis-μ-coordinated rhodium(II) diacetate complex (3) serves as a polymer-supported catalyst for alkene hydroformylation and hydrogenation

Preparation of heterocyclic phosphorus ylides containing the tetramic acid ring system and seven-membered ring vinylogues

Abstract Pyrolysis of amino acid-derived (α-aminoacyl)(ethoxycarbonyl)ylides results in ring closure with extrusion of ethanol to give novel five-, six- and seven-membered ring heterocyclic ylides.

Design, synthesis and pharmacological evaluation of pyrimidobenzothiazole-3-carboxylate derivatives as selective L-type calcium channel blockers.

L-type voltage gated calcium channels play essential role in contraction of various skeletal and vascular smooth muscles, thereby plays important role in regulating blood pressure. Dihydropyridine receptors have been targeted for development of newer antihypertensive agents, one of the structurally analogs nucleus dihydropyrimidines have been reported earlier by us as a potential agent toward development of calcium channel modulator. A pre-synthetic QSAR was run and on the basis of structure activity relationship a series of twenty three molecules was synthesized and studied by myosin light chain kinase assay (MLCK), Angiotensin Converting Enzyme (ACE) colorimetric assay, non-invasive blood pressure (NIBP) and invasive blood pressure (IBP) methods. Molecules with significant efficacy were studied for their single crystal X-ray diffraction, molecular docking, molecular dynamics and post-synthetic QSAR. The NIBP and IBP methods screened molecules with better percentage inhibition versus time compared to standard drug Nifedipine. The lead compound ethyl 2-methyl-4-(3-nitrophenyl)-4H-pyrimido [2,1-b] [1,3] benzothiazole-3-carboxylate (26) presented a triclinic structure with polymeric chain packing in lattice. 26 exhibited IC50 on MLCK assay of 2.1±1.7 μM with selectivity of L-type calcium channels and comparative to Nifedipine. It offered satisfactory physicochemical properties with partition coefficient of (ClogP) 4.64. Its pharmacokinetic profile is also good with Cmax at 0.40 μg/ml by oral route with Tmax reaching in 0.5 h which means in 30 min. 26 also exhibits superior t1/2 of 5.4 h and oral bioavailability of (F) 56.75% with an AUC0-∞ of 0.84 μg h/ml. Molecular docking studies indicates toward the interaction of lead compound via hydrogen bonds with Lys144, Glu181 and Asp183, it forms the Van der Walls interactions with Ser18, Asp20, Asn187, Pro185, Glu180, Glu181 and Arg10 with Glide score and Glide energy to be -3.602 and -47.098, respectively. Post-synthetic QSAR of newly synthesized molecules indicates toward improvement with respect to steric descriptor which contributed negatively in former series.