Rohit Mahar

Synthesis of Triazolo Isoquinolines and Isochromenes from 2-Alkynylbenzaldehyde via Domino Reactions under Transition-Metal-Free Conditions

We describe two simple straightforward syntheses of triazolo isoquinolines (3) and isochromenes (7) from 2-alkynylbenzaldehydes (1) as a common synthon. The synthetic strategy for 3 involves formation of the (E)-1-(2-nitrovinyl)-2-(alkynyl)benzene species 2 via condensation of synthon 1 with nitromethane followed by a [3 + 2] cycloaddition/extrusion of the nitro group/regioselective 6-endo cyclization domino sequence. In yet another strategy, the synthon 1 was condensed with nitromethane followed by electrophilic iodo cyclization of the resulting 2-nitro-1-(2-(alkynyl)phenyl)ethanol (6) to furnish iodo isochromene derivatives. The salient feature of the above two strategies involves formation of the corresponding heterocycles under metal-free conditions in good yields.

A metal-free tandem approach to prepare structurally diverse N-heterocycles: synthesis of 1,2,4-oxadiazoles and pyrimidinones

A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2,4-oxadiazoles and 2,6 disubstituted pyrimidin-4-ones is described via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids. The reactions occur at room temperature forming N-acylamidines which undergo tandem nucleophilic addition–deamination–intramolecular cyclisation to give the corresponding heterocyclic compounds in good to excellent yields. This one pot approach has led to the successful synthesis of the drug lead molecule, ataluren, 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl) benzoic acid in two steps.

Ruthenium(II)-catalyzed C–H activation/C–N bond formation via in situ generated iminophosphorane as the directing group: construction of annulated pyridin-2(1H)-ones

We describe an efficient and straightforward synthesis of annulated pyridin-2(1H)-ones following condensation of acyl azides with internal alkynes via the ruthenium-catalyzed ortho C–H bond activation. The reaction in DCE proceeds via in situ generation of iminophosphoranes as directing group-coordination of Ru with N-atom-ortho cyclometallation-insertion of an alkyne into the Ru–C bond-protonation-reductive elimination in a domino sequence. The role and stability of in situ generated iminophosphorane and ruling out the possibility for the benzamide involvement was established using 1H and 31P NMR experiments.

Synthesis of S-(−)-5,6-Dihydrocanthin-4-ones via a Triple Cooperative Catalysis-Mediated Domino Reaction

An enantioselective synthesis of S-(-)-5,6-dihydrocanthin-4-ones via a triple cooperative catalysis-mediated domino reaction having a broad substrate scope is reported. The reaction between substituted 1-formyl-9H-β-carbolines and terminal alkynes in the presence of catalytic amounts of Jorgensen-Hayashi catalyst, copper iodide, and Hunig base proceeded via a multicascade route, affording the title compounds in good yields and excellent ees with interesting mechanistic features. These compounds were assessed for in vitro antiplasmodial activity against P. falciparum strains. Additionally, 5,6-dihydrocanthin-4-ones are demonstrated to be a versatile precursor to different fused β-carboline derivatives via simple synthetic transformations.

Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity

Efficient and sensitive LC-MS/MS methods have been developed for the rapid screening and determination of bioactive compounds in different fruit parts of four Myristica species, viz., Myristica beddomeii, Myristica fragrans, Myristica fatua and Myristica malabarica. Twenty-one compounds were identified and characterized on the basis of their accurate mass and MS/MS fragmentation pattern using HPLC-QTOF-MS/MS and NMR analysis. Quantitative determination of five major bioactive compounds was performed using multiple-reaction monitoring mode with continuous polarity switching by UHPLC-QqQLIT-MS/MS. Moreover, in vitro antiproliferative activity of these Myristica species was evaluated against five human cancer cell lines A549, DLD-1, DU145, FaDu and MCF-7 using SRB assay. Seventeen phytoconstituents were identified and reported for the first time from M. beddomeii and sixteen from M. fatua. Quantification result showed highest total content of five major bioactive compounds in mace of M. fragrans. Evaluation of in vitro antiproliferative activity revealed potent activity in all investigated species except M. fragrans.

A Strategy for the Synthesis of Anthraquinone-Based Aryl-C-glycosides

An efficient and simple strategy for the synthesis of a diverse range of anthraquinone-based aryl-C-glycosides has been developed. It involves the sequential Diels-Alder reaction and oxidative aromatization with the preformed glycosyl diene and dienophiles. The glycosyl dienes were obtained from simple sugars by tandem one-pot substitution and elimination reaction.

Bioactivity guided isolation of oxypregnane-oligoglycosides (calotroposides) from the root bark of Calotropis gigantea as potent anticancer agents

Bioactivity guided isolation of oxypregnane-oligoglycosides (calotroposides) from the ethanolic extract of root bark of Calotropis gigantea (L.) Dryand. with purple flowers has been performed. Dereplication by NMR and LC-MS analysis confirmed the presence of oxypregnane-oligoglycosides (calotroposides) in the ethyl acetate fraction. One new (7) and six known calotroposides (1–6) were isolated from the most active ethyl acetate fraction of ethanolic extract of Calotropis gigantea and structure elucidation was accomplished by spectroscopic methods (IR, UV, MS and NMR). Isolated calotroposides were investigated for cytotoxic activity against six cancer cell lines (MDA-MB-231, MCF-7, LNCaP, HeLa, K562, and Caco-2) and a non-cancer cell line (HEK-293), where calotroposides 2, 4 and 5 showed highest cytotoxicity (IC50 8.49 ± 0.41 μM, 6.49 ± 0.15 μM and 9.65 ± 0.44 μM respectively) against MDA-MB-231. Conclusively, calotroposides 2, 4 and 5 have promising anticancer effect against aggressive breast cancer cells and can serve as leads for further structural exploration as anticancer moiety.

Pyranocarbazoles from Murraya koenigii (L.) Spreng. as antimicrobial agents

Abstract The bioassay guided fractionation of methanolic extract of Murraya koenigii (L.) Spreng. leaves resulted in the isolation of seven pyranocarbazoles. These were evaluated against four bacterial strains and ten Candida sp. including two matched pair of fluconazole sensitive/resistant clinical isolates. Out of seven, three i.e. Koenine (mk279), Koenigine (mk309) and Mahanine (mk347) exhibited significant antibacterial activity MIC90 3.12–12.5 μg/mL against bacterial strains Streptococcus aureus and Klebsiella pneumonia compared with standard drug Kanamycin MIC90 12.5 μg/mL. However, only mk309 was found active against variety of Candida species MIC90 12.5–100 μg/mL. It was observed that hydroxylation at C-6 and C-7 positions in the studied pyranocarbazoles activate the bioactivity. Simultaneously, decrease in Log P value compares with −H and −O−CH3 substituted derivatives. The study is focused on selective antifungal and antibacterial activity of pyranocarbazoles on bacterial strains S. aureus, K. pneumonia and variety of Candida species with structure activity relationship observations.