A preliminary
phytochemical investigation on the 90%
MeOH extract
from the twigs and needles of the vulnerable conifer Keteleeria
fortunei led to the isolation and characterization of 17
structurally diverse triterpen-26-oic acids, including nine previously
undescribed ones (fortunefuroic acids A–I, 1–9) featuring a rare furoic acid moiety in the lateral chain.
Among them, 1–5 are uncommon 9βH-lanostane-type triterpenoic acids. Friedo-rearranged triterpenoids 6 and 7 feature a unique 17,14-friedo-lanostane
skeleton, whereas 9 possesses a rare 17,13-friedo-cycloartane-type
framework. Their structures and absolute configurations were elucidated
by extensive spectroscopic (e.g., detailed 2D NMR) and computational
(NMR/ECD) calculations and the modified Mosher’s method. In
addition, the absolute structure of compound 1 was ascertained
by single-crystal X-ray diffraction analyses. Fortunefuroic acids
B (2), G (7), and I (9), along
with isomangiferolic acid (12) and 3α,27-dihydroxycycloart-24E-en-26-oic acid (14), exhibited dual inhibitory
effects against the adenosine triphosphate (ATP)-citrate lyase (ACL,
IC50s: 5.7–11.4 μM) and acetyl-CoA carboxylase
1 (ACC1, IC50s: 7.5–10.5 μM), both of which
are key enzymes for glycolipid metabolism. The interactions of the
bioactive triterpenoids with both enzymes were examined by molecular
docking studies. The above findings reveal the important role of protecting
plant species diversity in support of chemical diversity and potential
sources of new therapeutics for ACL-/ACC1-associated diseases.