Synthesis and antiproliferative activity of 6-naphthylpterocarpans

Szappanos, Ádám and Mándi, Attila and Gulácsi, Katalin and Lisztes, Erika and Tóth, István Balázs and Bíró, Tamás and Antus, Sándor and Kurtán, Tibor (2020) Synthesis and antiproliferative activity of 6-naphthylpterocarpans. ORGANIC & BIOMOLECULAR CHEMISTRY, 18. pp. 2148-2162. ISSN 1477-0520

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Abstract

The Heck-oxyarylation of racemic 2-(1-naphthyl)- and 2-(2-naphthyl)-2H-chromene derivatives were carried out resulting diastereoselectively in (6S*,6aR*,11aR*)-6-(1-naphthyl)- and 6-(2-naphthyl)-pterocarpans as major products and bridged (6R*,12R*)-6,12-methanodibenzo[d,g][1,3]dioxocine derivatives as minor products. Antiproliferative activity of two 6-naphthylpterocarpans was identified by MTT assay against A2780 and WM35 human cancer cell lines with low micromolar IC50 values. The measured 0.80 and 3.51 μM IC50 values of the (6S*,6aR*,11aR*)-6-(1-naphthyl)pterocarpan derivative with 8,9-methylenedioxy substitution represent the best activities in the pterocarpan family. Enantiomers of the pterocarpan and dioxocine derivatives and their chiral 2-naphthylchroman-4-one and 2-naphthyl-2H-chromene precursors were separated by HPLC using chiral stationary phase. HPLC-ECD spectra were recorded and absolute configuration and low-energy solution conformations were determined by TDDFT-ECD calculations. Characteristic ECD transitions of the separated enantiomers were correlated with their absolute configuration.

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