Two Novel Myrinsol Diterpenes from Euphorbia prolifera

Two novel diterpenes, Euphorprolitherin A (1) and Euphorprolitherin B (2), were isolated from the roots of Euphorbia prolifera. Their structures were elucidated on the basis of spectroscopic methods.

Two new antitumor diterpenes from Pinus sylvestris

Two new diterpenes, 15-ethyl-18-methyl pinifolate （1） and 18-hydroxy-labda-8（17）, 13E-dien-15-acetate （2）, were isolated from the needles of Pinus sylvestris. Their structures were elucidated by spectroscopic methods, including 2D-NMR spectra. Compound 1 exhibited the significant cytotoxic activity against the human carcinoma cell lines Hela, SK-N-SH and BEL-7402 in vitro.

Characterization of phloroglucinol derivatives and diterpenes in Euphorbia ebracteolata Hayata by utilizing ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Euphorbia ebracteolata Hayata （E. ebracteolata） is a Chinese herbal medicine used for the treatment of tumor diseases. An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS） based chemical profiling approach was established for the rapid separation and characterization on phloroglucinol derivatives and diterpenes in E. ebracteolata. Three phloroglucinol derivatives and nine diterpenes were identified by exact mass measurement and were further confirmed by Ms2 data. In addition, the chemical profiles of six compounds were acquired by reference standards. Furthermore, the fragmentation rules of phloroglucinol derivatives and diterpenes of E. ebracteolata were analyzed, and each chromatographic peak was classified.

Isolation and Crystal Structure of Ent-kaurane Diterpenes from Rubus corchorifolius L. f.

In this study, ent-Kaurane-3β,16β,17-trioi （1） and ent-kaurane-2a,16β,17-triol （2）, were isolated from the leaves ofRubus corchorifolius L. f. Their structures were elucidated based on extensive spectroscopic analysis. NMR experiments identified the two compounds and X-ray crystallographic analysis confirmed their crystal structures. The crystal of 1 belongs to monoclinic with space group P21 and a = 10.7641（3）, b = 7.2789（3）, c = 11.7862（4） A, β = 95.275（3）°, V = 919.55（6） A3, Z = 2, C20H34O4, Mr = 322.49 g/mol, Dc = 1.230 g/m3, F（000） = 376, 2 = 1.54178 A,μ = 0.661 mm-1, R = 0.0319, and wR = 0.0811 for 10889 observed reflections （I〉 2σ（I））. The crystal of 2 is classified as orthorhombic with space group P212121 and a = 10.7641（3）, b = 12.72224（19）, c = 21.3929（3） A, V= 1748.94（4） A3, Z= 4, C20H3404, Mr = 322.47, De = 1.225 Mg/m3 F（000） = 712, λ = 1.54184 A,μ = 0.625 mm-1, R = 0.0303 and wR = 0.0759 for 10470 observed reflections （1〉 2σ（I））. Meanwhile, the compound revealed low inhibitory activities toward HepG2, MCF-7, and SCG-7901 cells.

FIVE NEW DITERPENES FROM EUPHORBIA SIEBOLDIANA

Five new diterpenes were isolated from Euphorbia sieboldiana and identified as atis-16-en-13(S)-hydroxy-3,14-dione(Ⅰ),atis-16-en- 14-oxo-13(S),3 β-diol(Ⅱ),atisane-3-oxo-16α,17-diol(Ⅳ),atisane-3β ,16α,17-triol(Ⅴ)and atisane-3β-acetyl-16α,17-diol(Ⅵ)based on the chemical,spectral evidences and X-ray diffraction.

A Concise Approach to the Synthesis of Carnosic Acid Type Diterpenes

10-vinyl-8,11,13-podocatriene 8, which is a modal of Carnosic acid type diterpenes, has been synthesized by an expeditious convergent synthetic approach.

Two Labdane Diterpenes from Leonurus heterophyllus

Two new labdane diterpenoids named heteronone A （1） and heteronone B （2） were isolated from the aerial parts of Leonurus heterophyllus Sweet. Their structures were established by various spectroscopic means, and the structure of heteronone A is confn-med by X-ray diffraction analysis.

New jatropholane-type diterpenes from Jatropha curcas cv.Multiflorum CY Yang

Three new jatropholane-type diterpenoids,jatropholones C-E(1-3),along with seven other known compounds,including sikkimenoid B(4),jatrophaldehyde(5),epi-jatrophaldehyde(6),epi-jatrophol(7),jatrophol(8),jatropholone A(9),and jatropholone B(10),were isolated from the roots of a natural cultivar of Jatropha curcas(J.curcas cv.Multiflorum CY Yang).The structural elucidations of 1-3 were accomplished by extensive NMR analysis.Compounds 4,6,and 8 demonstrated inhibition activity against the microorganisms with the MIC values from 0.10 to 0.18 mg/mL.

Five New Guanacastane-Type Diterpenes from Cultures of the Fungus Psathyrella candolleana

Five new guanacastane-type diterpenes,named guanacastepenes P–T(1–5),were isolated from cultures of the fungus Psathyrella candolleana.Their structures were elucidated on the basis of extensive spectroscopic methods.All of the compounds were tested for their 11b-hydroxysteroid dehydrogenase(11b-HSD1)inhibitory activity.Compound 3 exhibited inhibitory activity against both human and mouse isozymes of 11b-HSD1 with IC50 values of 6.2 and 13.9 lM,respectively.

Two new brominated diterpenes from Laurencia decumbens

Two new brominated diterpenes, namely, laurendecumtriol and 11-deacetylpinnaterpene C, were isolated and identified from the marine red alga Laurencia decumbens. Their structures were established on the basis of various NMR spectroscopic techniques and HR-ESI-MS analyses.

Two New Diterpenes from Helianthus annuus L.

Two new diterpenes, 2β, 16β-ent-kaurane diol, 15α, 16α-epoxy-17β-al-ent-kaurane- 19-oic acid were isolated from Helianthus annuus L. Their structures were determined by spectroscopic evidences.

Sustainable biosynthesis of valuable diterpenes in microbes

Diterpenes,or diterpenoids,are the most abundant and diverse subgroup of terpenoids,the largest family of sec-ondary metabolites.Most diterpenes possess broad biological activities including anti-inflammatory,antiviral,anti-tumoral,antimicrobial,anticancer,antifungal,antidiabetic,cardiovascular protective,and phytohormone activities.As such,diterpenes have wide applications in medicine(e.g.,the anticancer drug Taxol and the antibiotic pleuromutilin),agriculture(especially as phytohormones such as gibberellins),personal care(e.g.,the fragrance sclareol)and food(e.g.,steviol glucosides as low-calorie sweeteners)industries.Diterpenes are biosyn-thesized in a common route with various diterpene synthases and decoration enzymes like cytochrome P450 oxidases,glycosidases,and acyltransferases.Recent advances in DNA sequencing and synthesis,omics analysis,synthetic biology,and metabolic engineering have enabled efficient production of diterpenes in several chassis hosts like Escherichia coli,Saccharomyces cerevisiae,Yarrowia lipolytica,Rhodosporidium toruloides,and Fusarium fujikuroi.This review summarizes the recently discovered diterpenes,their related enzymes and biosynthetic pathways,particularly highlighting the microbial synthesis of high-value diterpenes directly from inexpensive carbon sources(e.g.,sugars).The high titers(>4 g/L)achieved mean that some of these endeavors are reaching or close to commercialization.As such,we envisage a bright future in translating microbial synthesis of diterpenes into commercialization.

Daphnane-type diterpenes from genus Daphne and their anti-tumor activity

Daphnane-type diterpenenoids are the major biologically active constituents in the genus Daphne.We find that there are about 101 Daphnane-type diterpenes in this genus,most of those compounds show different degrees of inhibitory effect on various cancer cell.Some of them have been studied in depth and the potent molecular mechanisms might be associated with modulation of different cell-signaling pathways.In addition,some compounds of this type also can inhibit the synthesis of protein and DNA.Absolutely,the anti-tumor activity of Daphnane-type diterpenes is worthy of attention.Unfortunately,most of the current research on the activity of these compounds is focused on simple drug efficacy,and its in-depth mechanism research is far from enough.On the other point of view,there still exists wide growing space on the depth of these compounds.

Anticancer activity of diterpenes and steroids from Eunicella singularis against two- and three-dimensional breast cancer cell models

Objective: To investigate the anticancer activity of two diterpenes [palmonine F (C1) and palmonine D (C2)] and three steroids [cholesta-5,22-dien-3β-ol (C3), stigmasterol (C4) and 5α-cholest-5-en-3β-ol (C5)], isolated from the Mediterranean gorgonian Eunicella singularis, against MCF-7 breast cancer cell line. Methods: This study was performed on standard monolayer two-dimensional (2D) model to evaluate apoptosis by means of AnnexinV-FITC/PI flow cytometry and on three-dimensional (3D) spheroid model using Celigo imaging cytometer for spheroids size analysis. Results: Results indicated that both diterpenes and steroids exhibited an important apoptotic activity in a concentration-dependent manner with EC50 values of 13, 49, 30, 66 and 65 μg/mL for C1, C2, C3, C4 and C5, respectively. Treatment of MCF-73D cell model with C1–C5 induced growth regression of spheroids in a concentration-dependent manner similar to the clinical anti-breast cancer drug Taxol;over ten days of incubation, growth rates were < 1.5 at Day 10 with all tested compounds at 200 μg/mL. Conclusions: The present study indicates that the two diterpenes C1 and C2 and the three steroids C3, C4 and C5, isolated from Eunicella singularis, might be used as anti-breast cancer candidate drugs for further development.

Lignans and diterpenes isolated from Tirpitzia ovoidea and their biological activities

A new lignan, tirpitzin A(17) together with 20 known compounds(1-16, and 18-21) were isolated from the ethyl acetate soluble fraction of ethanol extract of the aerial parts of Tirpitzia ovoidea. The structure of new compound was elucidated by means of spectroscopic analysis. Of the known compounds, 7-21 were isolated from Linaceae family for the first time. The pharmacological activity of the crude extracts was tested using a mouse inflammation model induced by dimethyl benzene. The results demonstrated that the ethyl acetate soluble fraction had anti-inflammatory activity. Moreover, the cytotoxic and anti-inflammatory activities of some compounds were studied. The new compound 17 showed moderate cytotoxic effect against Bx PC-3 cell line(IC_50 = 19.51μmol·L^(-1)) and Compound 10 showed significant cytotoxicity against Hep G2, HL-60, U87 and Bx PC-3 cell lines with IC_50 values in the range 4.2-8.3μmol·L^(-1). Additionally, Compounds 2, 10, 11, and 13 exhibited potent inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages at the concentration of 50μmol·L^(-1).

A convergent approach to the tetracyclic core of atisane diterpenes

Atisane diterpenes are biologically interesting natural products. We report here a convergent approach to construct the tetracyclic core of the atisane skeleton. The two segments were assembled through a Wittig reaction, while an intramolecular Aldol condensation served as the key step to furnish the tetracyclic skeleton.

New cyclopiane diterpenes with anti-inflammatory activity from the sea sediment-derived fungus Penicillium sp.TJ403-2

Three new rare cyclopiane diterpenes(1-3),together with thirteen known compounds(4-16),were isolated and identified from a sea sediment-derived fungus Penicillium sp.TJ403-2.The planar and relative structures of compounds 1-3 were elucidated by HRESIMS,one-and two-dimensional NMR analyses,and their absolute configurations were further established by X-ray crystallography experiment.Compounds 1-3 were evaluated for the anti-inflammatory activity against LPS-induced NO production,and compound 1 showed notable inhibitory potency with an IC50 value of2.19±0.25μmol/L,which was three fold lower than the positive control indomethacin(IC50=8.76±0.92μmol/L).Further Western blot and immunofluorescence experiments demonstrated its mechanism of action to be that 1 inhibited the NF-κB-activated pathway,highlighting it as a promising starting point for the development of new anti-inflammatory agents.

Study on the regulatory effect of liver X receptor in HEK293 cells by six main diterpene esters in Semen Euphorbiae

Background:To study the effects of the main diterpene esters in Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)on the transcriptional activity and protein expression of liver X receptor(LXR).Methods:The effect of the main diterpene ester components in Semen Euphorbiae on the viability of HEK293 cells were studied by MTT assay.The LXR-Luc plasmid vector was transfected into HEK293 cells and treated with Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)for 24 h.The effect of the main diterpene ester components of Semen Euphorbiae on LXR-Luc luciferase activity was investigated by dual luciferase reporter gene system,and the expression of LXRαprotein was detected by Western Blot.Results:Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)could significantly reduce the relative luciferase activity(RLU)of LXRα,and the expression level of LXRαprotein was significantly down-regulated.Conclusion:Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)can inhibit the expression of LXR protein level,which may be achieved by inhibiting the transcriptional activity of LXR.

New ent-kaurane diterpenes with chiral epoxyangelate moieties from Wedelia prostrata

Four new ent-kaurane diterpenes with chiral epoxyangelate moieties, (2′R,3′R)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (1), (2′S,3′S)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (2), (2′S,3′R)-3 a- (2',3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (3) and (2′R,3′S)-3α- (2′,3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (4), along with eight known diterpenes (5-12), were isolated from Wedelia prostrata. The absolute configurations of the new structures were determined by X-ray crystallography,ECD calculations and chemical methods. All compounds were evaluated for their cytotoxicity activities on human HepG-2 cells,with IC_(50) values of 11.72 ±0.22 μmol/L to 54.75±1.12 μmol/L.

VASORELAXANT DITERPENES: FROM TRADITIONNAL MEDICINE TO NEW INHIBITORS OF VOLTAGE-DEPENDANT CALCIUM CHANNELS

Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urinary infections)and to treat fever associated with malaria.We analysed the in vitro and in vivo vasorelaxant activity