Hexahydroazulene-2(1 H )-one Sesquiterpenoids with Bridged Cyclobutane, Oxetane, and Tetrahydrofuran Rings from the Stems of Daphne papyracea with α-Glycosidase Inhibitory Activity.

Chemical investigation of an alcoholic extract from the stem of Daphne papyracea ("Xuehuagou") led to the isolation of the tetracyclic sesquiterpenoid daphnepapytone A ( 1 ), containing a unique caged skeleton with a cyclobutane ring having three tetrasubstituted chirality centers. Also isolated were new guaiane sesquiterpenoids, namely, daphnepapytones B-H ( 2 - 8 ), and one 1,5-diphenylpentanone 2-hydroxy-5-oxo-daphneone ( 9 ), together with 26 known compounds. The cyclic metabolites share a 5-isoprenyl-hexahydroazulene-2(1 H )-one skeleton with different substitution patterns and a bridged cyclobutane, oxetane, or tetrahydrofuran ring. The planar structures and relative configuration of the new compounds were elucidated on the basis of spectroscopic analysis aided by DFT ¹³ C NMR calculations. The absolute configurations of 1 - 7 were determined by X-ray single-crystal diffraction or TDDFT-ECD calculations. Daphnepapytones A and C ( 1 and 3 ), 2-hydroxy-5-oxodaphneone ( 9 ), daphnenone ( 10 ), daphneone ( 11 ), and 3-methyldaphneolone ( 12 ) showed α-glycosidase inhibitory activity, with IC ₅₀ values of 159.0, 102.3, 139.3, 43.3, 145.0, and 126.1 μM, respectively.