A previously undescribed triterpenoid (fortunefuroic acid J, 1) was isolated from the endangered conifer Keteleeria hainanensis, along with 20 other known terpenoids. Compound 1 is characterized by an unusual 3,4-seco-9βH-lanost-3-oic acid motif, featuring a rare furoic acid moiety in its lateral chain. The structure elucidation of this compound was achieved through a combination of spectroscopic and computational methods. The C-15 epimers of 15-methoxypinusolidic acid (15R-8 and 15S-9) were successfully separated and identified for the first time. Compound 1 demonstrated dual inhibitory effects against ATP-citrate lyase (ACL, IC50: 0.92 μM) and acetyl-CoA carboxylase 1 (ACC1, IC50: 10.76 μM). Compounds 2 and 11 exclusively inhibited ACL, exhibiting IC50 values of 2.64 and 6.35 μM, respectively. Compound 1 is classified among the fortunefuroic acid-type compounds, previously isolated from K. fortunei, distinguished by the presence of a rare furoic acid moiety in their lateral chain. The chemotaxonomic significance of the 9βH-lanost-26-oic acids in Keteleeria was briefly discussed. These findings highlight the importance of conserving plant species diversity, thereby enhancing the exploration of structurally diverse compounds and potential avenues for developing new therapeutics targeting ACL/ACC1-associated diseases.
Forrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels-Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC50 s <5 μM) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.
Parrotia subaequalis, an endangered Tertiary relict tree native to China and a member of the Hamamelidaceae family, is one of several host plant species in this family that exhibit unique ecological habits, such as gall formation. Tree galls are the results of complex interactions between gall-inducing insects and their host plant organs. The formation of galls may serve to protect other regions of the plant from potential damage, often through the production of phytoalexins. In this study, a preliminary investigation was carried out on the metabolites of the 90% MeOH extract derived from the closed spherical galls on the twigs of P. subaequalis. Consequently, nine previously undescribed benzofuran-type and dibenzofuran-type phytoalexins (parrotiagallols A-I, 1-9, respectively) were isolated and characterized, along with several known miscellaneous metabolites (10-17). Their chemical structures and absolute configurations were elucidated using spectroscopic methods, a combination of calculated and experimental electronic circular dichroism data, and single crystal X-ray diffraction analyses. Among these compounds, 1 and 2 are identified as neolignan derivatives, while compounds 3-5 are classified as 9,10-dinorneolignans. Compound 6 represents a rare 2,3-seco-neolignan, and compounds 7-9 are dihydroxy-dimethyl-dibenzofuran derivatives. Parrotiagallol A (1) showed considerable antibacterial activity against Staphylococcus aureus, with an MIC value of 14 μM. Additionally, parrotiagallol E (5) and methyl gallate (17) exhibited inhibitory effects against ATP-citrate lyase (ACL), a potential therapeutic target for hyperlipidemia, with IC50 values of 5.1 and 9.8 μM, respectively. The findings underscore that galls not only serve as physical defense barriers but also benefit from the chemical defense system of the host plants. These insights provide avenues for exploring potential new therapeutic agents for S. aureus infections and ACL-related diseases, while also promoting scientific conservation strategies for P. subaequalis.