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 anti-proliferative activity. Novel products were afforded in excellent yields (72-96%) within 20-90 min at 62 degrees C using flavonoid aldehydes, homoallylic alcohols, p-TSA center dot H2O (catalyst and reagent) and MS 4 angstrom in CHCl3. Deprotection of tosyl group was achieved with TFA (catalyst and solvent) at 140 degrees 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 (Hep3 beta, 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 mu M, respectively) to the reference drug doxorubicin (IC50 7.6 +/- 0.9 mu M) against the MCF-7 cancer cell line. Compound 3zb was found equally active as the standard drug (IC50 4.48 +/- 2.1 mu M) against the Hep3 beta cell line and compounds 3c and 3q showed moderate cytotoxicity (IC50 10.40 +/- 1.1, 12.9 +/- 1.7 mu M, respectively) against the HeLa cell line. (C) 2014 Elsevier Masson SAS. All rights reserved.