Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization.

A simple, efficient and highly diastereoselective one-pot three-component synthesis of functionalized 2,6-disubstituted-4-tosyloxytetrahydropyrans was performed. The synthesis features an optimized Prins cyclization in which an aromatic homoallylic alcohol, an aromatic/aliphatic aldehyde, and p-toluenesulfonic acid (catalyst and reagent) are reacted in the presence of molecular sieves (MS) 4 Å at reflux in dichloromethane to afford excellent yields (72-96%) within short reaction times (20-90 min). The MS 4 Å-promoted synthesis proved to be versatile enough to provide an array of symmetrical and unsymmetrical tetrahydropyran derivatives in economical manner. Furthermore, cleavage of the 4-tosyl group under mild conditions afforded 4-hydroxytetrahydropyran in excellent yields (95-96%).

Synthesis of flavonoids based novel tetrahydropyran conjugates (Prins products) and their antiproliferative activity against human cancer cell lines.

Following our previously reported Prins cyclization strategy, a series of novel and highly functionalized flavonoid based THPs (Prins products) were designed, synthesized and evaluated for their antiproliferative activity. Novel products were afforded in excellent yields (72-96%) within 20-90 min at 62 °C using flavonoid aldehydes, homoallylic alcohols, p-TSA·H2O (catalyst and reagent) and MS 4 Å in CHCl3. Deprotection of tosyl group was achieved with TFA (catalyst and solvent) at 140 °C to obtain 4-hydroxytetrahydropyrans and further reaction of 4-hydroxytetrahydropyrans with cinnamoyl chloride afforded 4-cinnamate tetrahydropyrans under neat condition. Synthesized compounds evaluated against human cancer cell lines (Hep3ß, MCF-7 and Hela), have shown moderate to good antiproliferative activity in vivo. Compounds 3q and 3zb exhibited similar cytotoxicity (IC50 6.6 ± 1.4, 6.9 ± 1.0 µM, respectively) to the reference drug doxorubicin (IC50 7.6 ± 0.9 µM) against the MCF-7 cancer cell line. Compound 3zb was found equally active as the standard drug (IC50 4.48 ± 2.1 µM) against the Hep3ß cell line and compounds 3c and 3q showed moderate cytotoxicity (IC50 10.40 ± 1.1, 12.9 ± 1.7 µM, respectively) against the HeLa cell line.

Design, synthesis and antiproliferative activity of functionalized flavone-triazole-tetrahydropyran conjugates against human cancer cell lines.

Under optimized reaction conditions, an efficient synthetic method has been developed to afford the functionalized flavone-triazole-tetrahydropyran conjugates via click reactions. The Cu-catalyzed 1,3-dipolar cycloaddition reaction gave the pure products, 5-iodo- and 5-H-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (90-98%) within 1-3 h. Further, Pd-catalyzed Suzuki coupling of 5-iodo-1,2,3-triazoles with phenylboronic acids afforded 5-phenyl-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (93-95%) in 4-5 h. Products (3a-l, 4a-j) were screened in vitro for their anti-proliferative activity against three human cancer cell lines (MDA-MB 231, KCL22 and Hela). Compounds 3c, 3g, 3i, 3j, 4c and 4h have shown better cytotoxicity (IC50 0.61-1.68 µM) than the reference drugs. Compounds 4e (IC50 0.70 µM), 3j (IC50 0.61 µM) and 4d (IC50 0.65 µM) exhibited anti-proliferative activity better than the reference drugs against the MDA-MB 231 cells, KCL22 cells and HeLa cells respectively.

Synthesis and antibacterial and antifungal evaluation of some chalcone based sulfones and bisulfones.

Two series of chalcone based sulfone and bisulfone derivatives were synthesized using chalcone, thiophenol and sodium metal at room temperature, followed by oxidation of chalcone sulfides with m-CPBA at 0 °C in a novel method. Both sulfones and bisulfones were evaluated for their antimicrobial activities against Aspergillus niger and Candida albicans (yeast), Bacillus subtilis and Staphylococcus aureus (Gram (+) bacteria) and Pseudomonas aeruginosa and Salmonella typhimurium (Gram (-) bacteria) strains. Among them, compounds 2c, 3c, 6c, 7c, 8c and 9c have shown high antifungal activity against C. albicans compare to reference drugs viz. Amphotericin-B and Nystatin. Compound 1c has shown slightly better antibacterial activity against B. subtilis and compounds 5c, 6c and 7c have shown excellent antibacterial activity against S. typhimurium in compare to reference drugs Ampicillin and Kanamycin.