New chromane and chromene meroterpenoids from flowers of Rhododendron rubiginosum Franch. var. rubiginosum

Six new chromane and chromene meroterpenoids rubiginosins A-F (1-2, and 4-7), together with three known ones, rubiginosin G (3) and anthopogochromenes A and B (8-9),were isolated from the flowers of Rhododendron rubiginosum Franch. var. rubiginosum. Among them, 1-4 were the chromane ones derived from an intramolecular [2 + 2] cycloaddition of their respective chromene precursors, making a 6/6/6/4- or 6/6/5/4-ring fused scaffold. The absolute configuration of the chiral center at C-2 of 1-9 was determined as S by chromane/chromene helicity rule and X-ray crystallograph. Notably, more attention should be paid to 6-carboxyl derivatives, since the 6-carboxyl derivatives showed an abnormal diagnostic Cotton effect (CE) with respect to their normal diagnostic CE. Compounds 1-9 were tested for cytotoxicity against four cell lines (A549, HCT116, SK-HEP-1, and HL-60), and only 1, 3, 5, and 9 showed moderate cytotoxicity, while others were inactive, discovering the 6-carboxyl is crucial for their low cytotoxicity.