Angular dihydropyranocoumarins from the flowers of Peucedanum japonicum and their aldo-keto reductase inhibitory activities.

Twenty-one angular dihydropyranocoumarins and a linear furanocoumarin, including four previously undescribed compounds (1-4), were isolated from the flowers of Peucedanum japonicum (Umbelliferae). The structures of 1-4, along with their absolute stereochemistry, were determined to be (3'S,4'S)-3'-O-propanoyl-4'-O-(3‴-methyl-2‴-butenoyl)khellactone (1), (3'S,4'S)-3'-O-propanoyl-4'-O-(2‴-methyl-2‴Z-butenoyl)khellactone (2), (3'S,4'S)-3'-O-propanoyl-4'-O-(2‴-methylbutanoyl)khellactone (3), and (3'S,4'S)-3'-O-(2″-methylpropanoyl)-4'-O-(3‴-methyl-2‴-butenoyl)khellactone (4) using one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectroscopy, and electronic circular dichroism spectroscopy. In addition, the absolute configuration of the three angular dihydropyranocoumarins (5-7) was determined for the first time in this study. Among the previously reported compounds isolated in this study, 8 and 9 were isolated for the first time from the genus Peucedanum, whereas 10 and 11 were previously unreported and had not been isolated from P. japonicum to date. Furthermore, all isolated compounds were evaluated for their aldo-keto reductase 1C1 inhibitory activities on A549 human non-small-cell lung cancer cells. Compounds 10 and 12 exhibited substantial AKR1C1 inhibitory activities with IC values of 35.8 ± 0.9 and 44.2 ± 1.5 μM, respectively.