Absolute configuration assignments by experimental and theoretical approaches of ent-labdane- and cis-ent-clerodane-type diterpenes isolated from Croton glabellus

Abstract

The bioassay-guided fractionation of the moderately cytotoxic extract from Croton glabellus resulted in the isolation of bioactive compounds, which were characterized as austroinulin (2), 6-O-acetylaustroinulin (3), the acetonide artifact of 2 (4), and 3-O-methylkaempferol (9). In addition, a new natural cis-ent-clerodane lactone diterpene named marrubiagenin (1), trans-dehydrocrotonin (6), the epimeric mixture of cajucarinolide (7/8), and 5,7,3′,4′-tetrahydroxy-3-methoxyflavonoid (10) were also characterized and identified as nonbioactive compounds. The structures of all compounds were determined by analyses of their physical and spectroscopic data and by comparison with those reported in the literature. The absolute configuration assignment of 3 was carried out by means of the modified Mosher method and by the experimental and theoretical circular dichroism method establishing that 3 belongs to the ent-labdane diterpene series. Furthermore, the absolute configuration of 1 was established by analysis of its chiroptical properties concluding that 1 belongs to the cis-ent-clerodane diterpene series.Key words: Croton glabellus, ent-labdane-type diterpenes, cis-ent-clerodane-type diterpenes, circular dichroism, TD-DFT.