New acylphloroglucinols from a crude acetone extract of Eucalyptus camaldulensis Dehnh. leaf

Abstract

Acylphloroglucinols are well-known Eucalyptus secondary metabolites which exhibit a variety of structures and bioactivities. The investigation of a crude acetone extract of Eucalyptus camaldulensis leaves led to the isolation of two new acylphloroglucinols, eucalypcamals O and P (1 and 2) together with seven phloroglucinols (3-9), and a benzene derivative (10). Their chemical structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy. The absolute configurations of compounds 1 and 2 were established by comparison of experimental and calculated electronic circular dichroism (ECD) data. In the putative biosynthetic pathway, eucalypcamals O and P should be derived from hetero-Diels-Alder reaction between grandinol and trans-isoeugenol.

Camaldulensals A–C, the First Meroterpenoids Possessing Two Spatially Separated Formyl Phloroglucinols Conjugated to a Terpene Core from the Leaves of Eucalyptus camaldulensis Dehnh

“…aureus (MSSA and MRSA) among the seven compounds tested in this study. It is also almost twice as active as eucalrobusone F, the most active compound previously reported from E. camaldulensis . , Furthermore, 2 is twice as active compared to its regioisomer 3 suggesting that the position of formyl and/or isovaleryl substituents in the dihydropyran fused phloroglucinol affects activity. The regiochemistry of the acyl group in the potently active compound rhodomyrtone vs its acyl regioisomer rhodomyrtosone B points to the importance of acyl regiochemistry for antibacterial activity in acylphloroglucinols .…”

“…A small number of FPCs have previously been tested at independent laboratories and shown to possess comparable antibacterial activities (for example macrocarpals A and C/G). However, a recent study has reported antibacterial activities as MIC 50 (in μg/mL) and this resulted in macrocarpals A and B and eucalyptal A and the positive control caiprofloxacin being reported with activities 10 to 100-fold more potent than the those reported using the more generally accepted measure of MIC. ,,, Consequently, the activities of all compounds reported by Liu et al 2022 have been shifted by an order of magnitude to make for more meaningful comparisons . Furthermore, we have recently developed a tool to check the validity of NMR assignments for FPCs and the structures of the four new compounds eurobusones A–D, reported by Liu et al 2022 are questionable since their NMR data poorly matches with that predicted for their substructure classes .…”

“…Over 200 FPCs have been reported to date. , FPCs exhibit a wide range of biological activities, including granulation inhibition, combating bacterial, fungal, protozoan, , and viral infections, binding to TRH receptors-2 in rats, and cell toxicity properties. , Additionally, FPCs also act as feeding deterrents for both mammals and insects. , The majority of FPCs are phloroglucinol–meroterpenoids containing formyl or acyl moieties attached to the phloroglucinol core and conjugated to either mono- or sesquiterpenes. Most FPCs have been reported from Eucalyptus species with smaller numbers reported from Psidium , Rhodomyrtus , and Eugenia species. − Eucalyptus species are dominant features of the Australian landscape and are found across all habitat zones. Eucalypt forests cover 101 million hectares of the Australian landscape.…”

“…In two previous studies, some of our coauthors described 16 FPCs with antimicrobial activity and cytotoxicity from extracts derived from E. camaldulensis leaves obtained from plantations in Thailand. 19,20 However, classic open column chromatography could not separate all compounds in the extract due to their similar physical and chemical properties. Careful comparison of the 1D and 2D NMR spectroscopic data (Table 1) obtained for 1 with those reported for euglobal VII 26 revealed many similarities suggesting that 1 contains an acyl-formyl-phloroglucinol−bicyclogermacrene sesquiterpene moiety.…”

“…It is also the most widely planted eucalypt outside of Australia, where it is used for honey, charcoal, timber, and paper production. In two previous studies, some of our coauthors described 16 FPCs with antimicrobial activity and cytotoxicity from extracts derived from E. camaldulensis leaves obtained from plantations in Thailand. , However, classic open column chromatography could not separate all compounds in the extract due to their similar physical and chemical properties. An international collaboration has now allowed us to successfully purify other compounds from the leaf extract using preparative HPLC.…”