Bioassay-Guided Isolation of Two Eudesmane Sesquiterpenes from Lindera strychnifolia Using Centrifugal Partition Chromatography

In this study, a centrifugal partition chromatography (CPC) separation was applied to identify antioxidant-responsive element (ARE) induction molecules from the crude extract of Lindera strychnifolia roots. CPC was operated with a two-phase solvent system composed of n-hexane-methanol-water (10:8.5:1.5, v/v/v) in dual mode (descending to ascending), which provided a high recovery rate (>95.5%) with high resolution. Then, ARE induction activity of obtained CPC fractions was examined in ARE-transfected HepG2 cells according to the weight ratios of the obtained fractions. The fraction exhibiting ARE-inducing activity was further purified by preparative HPLC that led to isolation of two eudesmane type sesquiterpenes as active compounds. The chemical structures were elucidated as linderolide U (1) and a new sesquiterpene named as linderolide V (2) by spectroscopic data. Further bioactivity test demonstrated that compounds 1 and 2 enhanced ARE activity by 22.4-fold and 7.6-fold, respectively, at 100 μM concentration while 5 μM of sulforaphane induced ARE activity 24.8-fold compared to the control.     

Chemical composition and antimicrobial activity of the essential oils from flowers and leaves of Grindelia integrifolia DC

Essential oils from flowers and leaves of Grindelia integrifolia DC. were investigated for the first time in terms of chemical composition and antimicrobial activity. The GC-FID/MS analysis allowed for the identification of 58 and 72 volatiles, comprising 92.4 and 90.1% of the oils, respectively. The major components of the flower oil were α-pinene (34.9%) and limonene (13.1%), while myrcene (16.9%), spathulenol (12.3%), β-eudesmol (11.9%) and limonene (10.1%) dominated among the leaf volatiles. The antimicrobial activity, evaluated against 12 selected bacteria and fungus, was found moderate, with the strongest effect of both oils observed against C. albicans (MIC = MBC: 0.63 and 0.31 mg/mL for flower and leaf oil, respectively).     

Phytochemical Constituents and Ameliorative Effect of the Essential Oil from Annona muricata L. Leaves in a Murine Model of Breast Cancer

Annona muricata leaves are traditionally used as an anticancer plant in the world. The aim of this study was to evaluate the ameliorative effect of the essential oil from Annona muricata leaves (EOAm) in an experimental model of breast cancer and to determine the volatile constituents with gas chromatography-mass spectrometry (GC-MS). Thirty female rats were assigned to five groups: the control group; the DMBA (7,12-dimethylbenz[α]anthracene) group; and three groups received daily EOAm doses of 50, 100, and 200 mg/kg/day, plus DMBA, respectively. After 13 weeks of treatment, tumors were analyzed pathologically and biochemical markers in serum were noted. As a result, in GC-MS analysis, 40 compounds were identified and 4 of them were abundant: Z-caryophyllene (40.22%), followed by α-selinene (9.94%), β-pinene (8.92%), and β-elemene (7.48%). Furthermore, EOAm in a dose-dependent form produced a reduction in tumor frequency and the accumulated tumor volume was reduced by 50% and 71% with doses of 100 and 200 mg/kg, respectively. Serum levels of reduced glutathione (GSH) increased and malondialdehyde (MDA) decreased significantly compared to the DMBA group. Serum levels of vascular endothelial growth factor (VEGF) decreased significantly from 70.75 ± 7.15 pg/mL in the DMBA group to 46.50 ± 9.00 and 34.13 ± 11.50 pg/mL in groups treated with doses of 100 and 200 mg/kg, respectively. This study concludes that the EOAm leaves showed an ameliorative effect in a murine model of breast cancer.     

Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from Saussurea lappa (Decne.) C.B Clarke

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2–5 and 8–13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A–G (1–7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1–15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 μM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC₅₀ 0.73 ± 0.18 and 1.43 ± 0.54 μM, respectively. Structure-based molecular networking inspired the discovery of target compounds.     

Structural revision of peribysins C and D

Structural revision of the cell-adhesion inhibitory eremophilane sesquiterpenoid peribysins C and D is reported. A CAST/CNMR system is utilized in the reinvestigation of ¹³C NMR chemical shift values and structures, and geometric analyses with molecular and quantum mechanics calculations, and revalidation of NMR data support the revised structures.     

Silicon guided rearrangement of epoxydecalines to spirocyclic compounds. Synthesis of gleenol and axenol from carvone

The synthesis of the spirocyclic sesquiterpenes (−)-gleenol and (−)-axenol in enantiomerically pure form has been achieved starting from R-(−)-carvone. The key step is the silicon guided acid-promoted rearrangement of a 9-trimethylsilyl-5,6-epoxy-noreudesmane prepared from 3-trimethylsilyldihydrocarvone in several steps involving Robinson annulation, enone deconjugation and epoxidation. Acid treatment of the epoxy-noreudesmane gave a norspiroaxane as the main product, which was used as intermediate for the synthesis of two naturally occurring sesquiterpenes gleenol and axenol.     

Two New Highly Oxidized Humulane Sesquiterpenes from the Basidiomycete Lactarius mitissimus

Two new highly oxidized humulane sesquiterpenes, mitissimols F ( 1 ) and G ( 2 ), were isolated from the fruiting bodies of Lactarius mitissimus. Their structures were elucidated by using extensive spectroscopic techniques including 1D‐ and 2D‐NMR experiments. The absolute configuration of mitissimol F ( 1 ) was determined by ¹H‐NMR resolution of its diastereoisomeric α‐methoxy‐α‐(trifluoromethyl)benzeneacetates (MTPA). It was shown to be (1S,3E,6S,8R,9R,10S,11R)‐8,9 : 10,11‐diepoxy‐1,6‐dihydroxyhumul‐3‐en‐5‐one (=(1S,2R,4R,6S,8E,11S,12R)‐6,11‐dihydroxy‐1,6,10,10‐tetramethyl‐3,13‐dioxatricyclo[10.1.0.0^2,4]tridec‐8‐en‐7‐one).     

Isolation and structure elucidation of new sesquiterpenes of protoilludane origin from the fungus Clavicorona divaricata

Four novel sesquiterpenes of protoilludane origin, divaricatines A 3a and B 3b, 7-epitsugicoline H 4a and tsugicoline M 5a have been isolated from agar cultures of the fungus Clavicorona divaricata (Basidiomycetes). Their structures were elucidated by means of NMR studies and chemical correlations. All the metabolites are weakly active on bacteria but inhibited the germination of the water cress Lepidium sativum. A possible mechanism of their formation from the protoilludane tsugicoline A 1 is suggested. A fifth metabolite, the norsesquiterpene tsugicoline L 2b, was also isolated from the same fungus together with the known tsugicoline I 2a.     

New Eremophilane Sesquiterpenes from a Rhizome Extract of Petasites hybridus

A total of 21 natural products, 1 – 21 , were isolated from a supercritical CO₂ extract of the rhizomes of Petasites hybridus. Thereby, seven new eremophilane (= (1S,4aR,7R,8aR)‐decahydro‐1,8a‐dimethyl‐7‐(1‐methylethyl)naphthalene) sesquiterpenes, compounds 4, 5, 9, 11, 12, 15 , and 17 , were identified. The new constituent 9‐hydroxyisobakkenolide ( 15 ) is the first representative of a group of compounds closely related to the well‐known, but rare, bakkenolides. Tsoongianolide B ( 18 ) and its degradation product ligularenolide ( 19 ) were found as new Petasites constituents as well. The known eremophilanolide 2 was isolated from a plant source for the first time and the oxofuranopetasin 16 was isolated for the first time from the rhizomes of P. hybridus, together with eight other known compounds. The C(8)‐epimeric 2‐[(tigloyl)oxy]eremophilanolides 3 and 8 could clearly be differentiated. All structures were established by extensive 1D‐ and 2D‐NMR experiments (Tables 1–3), and confirmed by in‐depth GC/MS and HPLC/MS experiments.     

Electron Transfer‐Initiated Epoxidation and Isomerization Chain Reactions of β‐Caryophyllene

The abundant sesquiterpene β‐caryophyllene can be epoxidized by molecular oxygen in the absence of any catalyst. In polar aprotic solvents, the reaction proceeds smoothly with epoxide selectivities exceeding 70 %. A mechanistic study has been performed and the possible involvement of free radical, spin inversion, and electron transfer mechanisms is evaluated using experimental and computational methods. The experimental data—including a detailed reaction product analysis, studies on reaction parameters, solvent effects, additives and an electrochemical investigation—all support that the spontaneous epoxidation of β‐caryophyllene constitutes a rare case of unsensitized electron transfer from an olefin to triplet oxygen under mild conditions (80 °C, 1 bar O₂). As initiation of the oxygenation reaction, the formation of a caryophyllene‐derived radical cation via electron transfer is proposed. This radical cation reacts with triplet oxygen to a dioxetane via a chain mechanism with chain lengths exceeding 100 under optimized conditions. The dioxetane then acts as an in situ‐formed epoxidizing agent. Under nitrogen atmosphere, the presence of a one‐electron acceptor leads to the selective isomerization of β‐caryophyllene to isocaryophyllene. Observations indicate that this isomerization reaction is a novel and elegant synthetic pathway to isocaryophyllene.