A comprehensive phytochemical investigation of the twigs/leaves and flower buds of Kolkwitzia amabilis, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (1-4 and 7-13), 20 triterpenoids (5, 6, and 14-31), and 8 phenylpropanoids (32-39). Among these, amabiliosides A (1) and B (2) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (3) and D (4) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-β-carboline-5-carboxylic acid moiety. Amabiliacids A (5) and B (6) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆11,13(18) transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound 2 exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC50 value of 9.6 μM. Lonicejaposide C (8), 3β-O-trans-caffeoyl-olean-12-en-28-oic acid (29), and (23E)-coumaroylhederagenin (31) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC50 values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3β-acetyl-ursolic acid (17) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC50 values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera Kolkwitzia and Lonicera within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases.
Secondary metabolites in plants of the same species, though originating from distinct geographical regions, frequently display both similarities and notable variations. A prior study on the vulnerable Chinese endemic conifer Keteleeria fortunei, collected from Yunnan province (KFYN), led to the isolation of fortunefuroic acids (FFAs) A-I. These compounds represent a unique class of triterpenoids characterized by a rare furoic acid moiety within the lateral chain. The distinct 23,27-epoxy-23,25(27)-dien-26-oic acid unit present in FFAs can be readily identified by characteristic proton NMR signals (δH-24: ca 6.36 ppm; δH-27: ca 7.97 ppm), a prominent ion fragment at m/z 125 in the EI-MS, and typical UV absorption peak around λmax 245 nm. In this study, an integrated approach was employed to dereplicate and isolate FFA-type compounds from K. fortunei collected from Fujian Province (KFFJ). This approach combined NMR, EI-MS, and LC-PDA-ESIMS data to detect and analyze compounds with molecular weights in the range of 464-468 Da, a distinguishing feature of FFA-type compounds. Consequently, six previously undescribed FFAs K-P (1-6) were obtained, alongside the re-isolation of FFAs A-D and H. Compound 1 exhibits a rare 17,14-friedo-cyclaorane type skeleton, while compound 2 is characterized as a 3,4-seco-cyclaorane-3,26-dioic acid. Compounds 3-6 are identified as derivatives of 9βH-lanost-26-oic FFAs. Additionally, a previously unreported lanost-26-oic acid derivative (7) was also identified, exhibiting an inhibitory effect on ATP-citrate lyase. Their chemical structures and absolute configurations were determined through spectroscopic analysis, GIAO NMR calculations combined with DP4+ probability analyses, and electronic circular dichroism calculations. The isolated FFAs have the potential to serve as chemotaxonomic markers for the genus Keteleeria within the Pinaceae family. This study marks the first application of integrated NMR/EI-MS/LC-PDA-ESIMS methods for both dereplication and the discovery of new natural products. Notably, the KFFJ samples were collected from a location approximately 1500 km away from that of KFYN. Understanding the impact of geographical origins on specialized metabolites may provide valuable insights into the sustainable utilization and conservation of endangered plant species.
Alcimaterpenoids A (1) and B (2), two pairs of racemic bis-denudaquinol-monoterpenoid meroterpenoids, were isolated and identified from Alcimandra cathcartii. Electronic circular dichroism (ECD) computations, GIAO 13C{1H} NMR (in conjunction with DP4+ probability analysis), and extensive 2D-NMR spectroscopic analysis techniques were used to determine their structures and absolute configurations. Structurally, compounds 1 and 2 are the first enantiomeric bis-denudaquinol-monoterpenoid meroterpenoids. Plausible biosynthetic pathways were briefly proposed. Compound (±)-1 exhibited moderate cytotoxic activity against the human PLC/PRF/5 cell line (IC50: 20.6 μM).