Eucalyptals D and E, new cytotoxic phloroglucinols from the fruits of Eucalyptus globulus and assignment of absolute configuration

Abstract

Two new phloroglucinols, named eucalyptals D (1) and E (2), along with a related known compound (euglobal-In-3, 3) were isolated from the fruits of Eucalyptus globulus. Their structures were established on the basis of extensive spectroscopic studies, revealing that they share a common 3,5-diformyl-isopentyl phloroglucinol unit, but each is instead coupled to a different sesquiterpenoid skeleton (aromadendrene in 1, cadinene in 2, and a spirosesquiterpene in 3). Compound 1 possessed an unusual seven-membered D ring with an ether bridge between C-2 of the aromadendrene moiety and C-2′ of the aromatic unit. The absolute configuration of the isolates was defined by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1–3 exhibited significant in vitro cytotoxicities against a few human cancer cell lines (Huh-7, Jurkat, BGC-823, and KE-97) using the CellTiter-Glo™ luminescent cell viability assay method.

New Formyl Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta

“…Meanwhile, the remaining two degrees of unsaturation and the observed four oxygenated carbons at C-3′, C-6, C-10, and C-11 ( δ C 168.4, 85.8, 71.2, and 74.6, respectively) revealed that there were two oxygen bridges in 2 . The diagnostic downfield shift of C-6 ( δ C 85.8) revealed its ether linkage to the deshielding benzene ring101117, and consequently the oxygen bridge between C-10 and C-11 was established to fulfil the unsaturated degree18. The ROESY correlations (Fig.…”

“…3) of H-6/H-8′a, H-6/Me-15, H-6/H-8 β , H-8 α /Me-12, and H-12′/H-7 revealed the α -oriented H-7′ and the β -oriented H-6, H-7, Me-14, and Me-15. In order to determine its absolute configuration, quantum chemical electron circular dichroism (ECD) calculation was applied1017, and indicated the 4 R , 6 R , 7 R , 10 S , and 7′ R configurations (Figure S1). …”

“…Three known FPMs, macrocarpal C20, eucalyptal D17, and euglobal V21, were also isolated from this plant. Their structures were confirmed by comparison of their spectroscopic data with values reported in literature.…”

“…7). The formation of carbocation in phloroglucinol precursor was thought to play a constructive role to trigger nucleophilic addition in the biosynthesis41117. Thereafter, the different ion migration in terpene units made the cyclization diversify in oxa-heterocyclic rings.…”

Configurational Assignments of Conformationally Restricted Bis-Monoterpene Hydroquinones: Utility in Exploration of Endangered Plants

“…The Amber* force field was used to define the initial geometries followed by PM6 [22] semiempirical optimizations. These conformers were subsequently used in hybrid DFT B3LYP/6-31G(d,p) calculations to obtain more accurate geometries in the gas phase and in MeCN employing the Conductor-like Polarizable Continuum Model [23,24]. The 24 lowest-energy conformers (Conformer 1-24, see Supplementary data 2) within an energy window of 50 kJ/mol were compared to the minimum-energy conformer which exhibited different intramolecular hydrogen bond interactions, involving the C-1 and C-3′ hydroxy groups and the C-12′ ester oxygen atoms.…”