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.

Keywords: Cytotoxicities; Eucalyptals; Eucalyptus globulus; Myrtaceae; Phloroglucinols.

Figure 1

The structures of phloroglucinol-coupled sesquiterpenes 1–4.

Figure 2

Key COSY ( ) and HMBC (H→C) correlations of 1.

Figure 3

Observed key NOE (H H) correlations of 1 and 2.

Figure 4

Simulated ECD spectra of 1–3 (after Boltzmann averaging) compared with the experimental CD spectra.

Figure 5

Hypothetical biosynthetic pathway of 1.