Structural determination of 3beta-stearyloxy-urs-12-ene from Maytenus salicifolia by 1D and 2D NMR and quantitative 13C NMR spectroscopy

Six pentacyclic triterpenoids, 3beta-stearyloxy-urs-12-ene (1), friedelin (2), 3beta-friedelinol (3), alpha-amyrin (4), beta-amyrin (5), and lupeol (6), have been isolated from the hexane extract of Maytenus salicifolia Reissek (Celastraceae) leaves. The molecular and structural formula as well as the stereochemistry of a new pentacyclic triterpene (1) were determined using data obtained from 1H and 13C NMR spectra, DEPT135 and by 2D HSQC, HMBC, COSY and NOESY experiments. The molecular formula C48H84O2 was established using quantitative 13C NMR, and the molecular weight (692 Da) was confirmed by elemental analysis and mass spectrometry (GC-MS).     

Triterpene Acids from the Leaves of Planchonella Duclitan (Blanco) Bakhuizan

From the methanolic extract of the leaves of Planchonella duclitan, 2α,3α,19α,23‐tetrahydroxy‐13,27‐cyclours‐11‐en‐28‐oic acid (1), myrianthic acid (2), 2‐hydroxyursolic acid (3), ursolic acid (4), pomolic acid (5), rotundic acid (6), and jacoumaric acid (7) were isolated, and their structures were elucidated on the basis of their spectroscopic analysis. Among them, compound 1 was a new cyclopropyl ursane‐type triterpene acid. Additionally, compounds 4 and 7 showed significant cytotoxicity toward human colorectal carcinoma cell line HT29 and human breast carcinoma cell line MCF‐7 with IC₅₀ values ranging from 5.8 ± 1.4 to 6.5 ± 1.9 μM.     

Triterpenoids from the Flowers of Salvia miltiorrhiza

A phytochemical investigation of the flowers of Salvia miltiorrhiza Bunge led to the isolation of two new oleanane‐ and ursane‐type triterpenoids, (3α)‐olean‐12‐ene‐3,23‐diol ( 1 ) and (3α)‐urs‐12‐ene‐3,23‐diol ( 2 ), as well as of four known triterpenoids. Their structures were elucidated on the basis of spectroscopic evidence, including 1D‐ and 2D‐NMR, HR‐MS, and the X‐ray analysis, and by comparison with literature data.     

Three new dihydro‐β‐agarofuran sesquiterpenes from the seeds of Maytenus boaria

As part of a project studying the secondary metabolites extracted from the Chilean flora, we report herein three new β‐agarofuran sesquiterpenes, namely (1S,4S,5S,6R,7R,8R,9R,10S)‐6‐acetoxy‐4,9‐dihydroxy‐2,2,5a,9‐tetramethyloctahydro‐2H‐3,9a‐methanobenzo[b]oxepine‐5,10‐diyl bis(furan‐3‐carboxylate), C₂₇H₃₂O₁₁, ( II ), (1S,4S,5S,6R,7R,9S,10S)‐6‐acetoxy‐9‐hydroxy‐2,2,5a,9‐tetramethyloctahydro‐2H‐3,9a‐methanobenzo[b]oxepine‐5,10‐diyl bis(furan‐3‐carboxylate), C₂₇H₃₂O₁₀, ( III ), and (1S,4S,5S,6R,7R,9S,10S)‐6‐acetoxy‐10‐(benzoyloxy)‐9‐hydroxy‐2,2,5a,9‐tetramethyloctahydro‐2H‐3,9a‐methanobenzo[b]oxepin‐5‐yl furan‐3‐carboxylate, C₂₉H₃₄O₉, ( IV ), obtained from the seeds of Maytenus boaria and closely associated with a recently published relative [Paz et al. (2017). Acta Cryst. C 73 , 451–457]. In the (isomorphic) structures of ( II ) and ( III ), the central decalin system is esterified with an acetate group at site 1 and furoate groups at sites 6 and 9, and differ at site 8, with an OH group in ( II ) and no substituent in ( III ). This position is also unsubstituted in ( IV ), with site 6 being occupied by a benzoate group. The chirality of the skeletons is described as 1S,4S,5S,6R,7R,8R,9R,10S in ( II ) and 1S,4S,5S,6R,7R,9S,10S in ( III ) and ( IV ), matching the chirality suggested by NMR studies. This difference in the chirality sequence among the title structures (in spite of the fact that the three skeletons are absolutely isostructural) is due to the differences in the environment of site 8, i.e. OH in ( II ) and H in ( III ) and ( IV ). This diversity in substitution, in turn, is responsible for the differences in the hydrogen‐bonding schemes, which is discussed.     

Salicassin,an Unprecedented Chalcone?Diterpene Adduct and a Quinone Methide Triterpenoid from Maytenus salicifolia

In continuation of our work on Maytenus salicifolia, we report herein the isolation and structural elucidation of two new compounds, salicassin ( 1 ), a diterpene‐chalcone adduct with an unprecedented C‐framework, and (16β)‐16‐hydroxypristimerin ( 2 ), a quinone methide triterpenoid. Their structures were elucidated on the basis of spectroscopic analysis, including 1D‐ and 2D‐NMR techniques (COSY, ROESY, HSQC, and HMBC). In addition, 22 known compounds were isolated and characterized by comparison of their spectra with reported data. Compound 2 , structurally related to the well known cytotoxic quinone methide triterpenoids, exhibited an antiproliferative effect on HeLa, A‐549, and HL‐60 human cell lines, with IC₅₀ values of 2.2, 3.2, and 2.7 μM , respectively.     

A dihydro‐β‐agarofuran sesquiterpene from Maytenus boaria

The natural compound (1S ,4S ,5S ,6R ,7R ,8R ,9R ,10S )‐6‐acetoxy‐4,9,10‐trihydroxy‐2,2,5a,9‐tetramethyloctahydro‐2H‐3,9a‐methanobenzo[b ]oxepin‐5‐yl furan‐3‐carboxylate, C₂₂H₃₀O₉, (I), is a β‐agarofuran sesquiterpene isolated from the seeds of Maytenus boaria as part of a study of the secondary metabolites from Chilean flora. The compound presents a central structure formed by a decalin system esterified with acetate at site 1 and furan‐3‐carboxylate at site 9. The chirality of the skeleton can be described as 1S ,4S ,5S ,6R ,7R ,8R ,9R ,10S , which is consistent with that suggested by NMR studies. Unlike previously reported structures of sesquiterpenes containing a pure dihydro‐β‐agarofuran skeleton, (I) exhibits a three‐dimensional hydrogen‐bonded network.     

First Total Synthesis of (−)‐Ligustiphenol

The first asymmetric total synthesis of (?)‐ligustiphenol is reported. The key step was conducted by exploiting a steric hindrance effect to control the formation of the adduct in a nucleophilic α‐Li‐phenolate addition reaction to the intermediate α‐oxo (?)‐menthyl ester. The synthesis is concise and feasible for the construction of analogous compounds and investigation of their biological activity.     

Chemical Constituents from Alafia Barteri Oliv. Leaves with Cytotoxic Activity

Methanol extract of Alafia barteri leaves showed cytotoxic activity on leukaemia carcinoma K562, and hepatic liver cancer cells WRL (IC₅₀ values 193.1 and 225.0 μM respectively). Isolation of the extract gave ursane triterpenoid, 28‐acety‐urs‐5,20‐dien‐2β,3β,24α‐triol, 1 , together with undecanol, 2 , stigmasterol, 3 and octadecanoic acid, 4 . The structures of these compounds were identified by spectroscopic analysis, including MS, 1D and 2D NMR, and supported with literature data. Compound 1 exhibited cytotoxic activity against K‐562 at 50 and 100 μM concentrations with IC₅₀ 74.22 μM, while compounds 2 , 3 and 4 showed low inhibition of WRL, MCF‐7 and COLO cell lines.     

Two New Sesquiterpene Polyol Esters from Celastrus angulatus

Two novel sesquiterpene polyol esters with a dihydro‐β‐agarofuran (=(3R,5aS,9R,9aS)‐octahydro‐2,2,5a,9‐tetramethyl‐2H‐3,9a‐methano‐1‐benzoxepin) skeleton, (1α,2α,4β,8α,9α)‐1,2,8,12‐tetrakis(acetyloxy)‐9‐(furoyloxy)‐4‐hydroxydihydro‐β‐agarofuran ( 1 ) and (1α,2α,6β,8α,9α)‐1,2,6,8,12‐pentakis(acetyloxy)‐9‐(benzoyloxy)dihydro‐β‐agarofuran ( 2 ), and the three known compounds (1α,2α,4β,6β,8α,9β)‐1,2,6‐tris(acetyloxy)‐9‐(benzoyloxy)‐4‐hydroxy‐8,12‐bis(isobutyryloxy)dihydro‐β‐agarofuran ( 3 ), (1α, 2α,4β,6β,8α,9β)‐1,2,6,8‐tetrakis(acetyloxy)‐9‐(furoyloxy)‐4‐hydroxy‐12‐isobutyryloxy)dihydro‐β‐agarofuran ( 4 ), and (1α,2α,4β,6β,8α,9β)‐1,2,6‐tris(acetyloxy)‐9‐(benzoyloxy)‐4‐hydroxy‐8‐(isobutyryloxy)‐12‐[(2‐methylbutanoyl)oxy]dihydro‐β‐agarofuran ( 5 ) were isolated from the root bark of Celastrus angulatus. Their chemical structures were elucidated by analyses of their MS and NMR data.     

NMR spectroscopic characterization of inclusion complexes comprising cyclodextrins and gallated catechins in aqueous solution: cavity size dependency

The structure of inclusion complexes of γ‐cyclodextrin (γ‐CD), (–)‐gallocatechin gallate (GCg), and (–)‐epigallocatechin gallate (EGCg) in D₂O was investigated using several NMR techniques. GCg formed a 1:1 inclusion complex with γ‐CD in which the A and C rings of GCg were inserted deep at the head of the A ring into the γ‐CD cavity from the wide secondary hydroxyl group side. In the 1:1 inclusion complex with GCg and γ‐CD, the GCg moiety maintained a conformation in which the B and B′ rings of GCg took both pseudoequatorial positions with respect to the C ring. The structure of the inclusion complex of GCg and γ‐CD obtained from NMR experiments supported well that determined from PM6 semiempirical SCF MO calculations. However, ¹H NMR experiments suggested that EGCg did not form any inclusion complex with γ‐CD in D₂O. The marked difference between GCg and EGCg in inclusion behavior toward γ‐CD may be explained in terms of the stabilization energy calculated with the PM6 method. Copyright © 2008 John Wiley & Sons, Ltd.     

New and Bioactive Sesquiterpenes from Schisandra sphenanthera

Three new sesquiterpenes, schisansphenins A ( 1 ) and B ( 2 ) and (?)‐γ‐cuparenol ( 3 ), were isolated from an acetone extract of the fruits of Schisandra sphenanthera. The known compound 4 was isolated for the frist time from a natural source. The structures of the isolated compounds were elucidated through extensive spectroscopic analyses, particularly 2D‐NMR experiments (¹H,¹H‐COSY, HMQC, HMBC, and NOESY). A plausible biogenetic pathway for schisansphenin B ( 2 ) is proposed. Compounds 2 and 3 significantly reduced activation of NF‐AT and NF‐κB in the luciferase‐reporter assay.     

Triterpene Saponins from the Leaves of Ilex pernyi

Eight new triterpene saponins, ilexpernosides C–J ( 1 – 8 , resp.), and eight known triterpene saponins were isolated from the 70% EtOH extract of the leaves of Ilex pernyi. The structures of the new compounds were elucidated by spectroscopic data and chemical degradation.     

A Mild and Rapid Synthesis of (Z)‐β‐Sulfonyl Enoates from Sodium Sulfinates and Propargyl Esters

Water‐promoted sulfonylation of propargyl esters leading to highly regioselective and stereoselective formation of (Z)‐β‐sulfonyl enoates in excellent yields, by a simple, mild, rapid and environmentally benign reaction procedure is reported.     

Development and validation of an ultra high‐performance liquid chromatographic method for the determination of a diastereomeric impurity in (+)‐pinoresinol diglucoside chemical reference substance

(+)‐Pinoresinol 4,4′‐di‐O‐β‐D ‐glucopyranoside ((+)‐PDG) is one of the major lignans with various pharmacological activities which could be isolated from Duzhong and other plant species. In this study, a diastereomeric impurity, (?)‐pinoresinol 4,4′‐di‐O‐β‐D ‐glucopyranoside ((?)‐PDG), the main impurity was identified in (+)‐PDG chemical reference substance (CRS) and a reliable chromatographic method for rapid purity determination of (+)‐PDG CRS was firstly developed. The optimal chromatographic condition was found to be using ACN/1,4‐dioxane–water (2.5:6:91.5, v/v/v) as mobile phase on a Waters Acquity UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) with column temperature of 37°C. The method was validated and applied to determine the chromatographic purity of five (+)‐PDG CRS samples. The content of (?)‐PDG in four commercial (+)‐PDG CRS was 8.47–20.30%, whereas no (?)‐PDG was detected in our in‐house prepared (+)‐PDG CRS in which purity was confirmed to be 99.80%. The above results confirmed that this method is fast and highly efficient for purity determination of the (+)‐PDG CRS.     

3-Oxo-12alpha-hydroxyfriedelane from Maytenus gonoclada: structure elucidation by (1)H and (13)C chemical shift assignments and 2D-NMR spectroscopy

The compounds 3-oxofriedelane (1), 3beta-hydroxyfriedelane (2), 3,11-dioxofriedelane (3), 3,16-dioxofrie delane (4) and 3-oxo-12alpha-hydroxyfriedelane (5) were isolated from the hexane extract of Maytenus gonoclada Mart. (Celastraceae) leaves. Structural formula and the stereochemistry of the new pentacyclic triterpene 3-oxo-12alpha-hydroxyfriedelane (5) were established through (1)H and (13)C NMR and DEPT 135 spectral data including 2D experiments (HMBC, HMQC, COSY, and NOESY) and mass spectrometry (GC-MS).     

Two New Lycopodine Alkaloids from Huperzia serrata

Two new lycopodine alkaloids, (12β)‐12‐hydroxyhuperzine G ( 1 ) and (5β,6β,15α)‐15‐methyllycopodane‐5,6‐diol ( 2 ), were isolated from the whole plants of Huperzia serrata, together with six known compounds, huperzines A, B, and G, phlegmariurine B, (8β)‐8‐hydroxyphlegmariurine B, and lycoposerramine D. Their structures were elucidated on the basis of spectroscopic analysis, including HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR, DEPT, ¹H,¹H‐COSY, HSQC, HMBC, and NOESY data.     

Validation of a high‐performance liquid chromatography method for the determination of (−)‐α‐bisabolol from particulate systems

A reversed‐phase high performance liquid chromatography method has been developed and validated for determination and quantitation of the natural sesquiterpene (−)‐α‐bisabolol. Furthermore the application of the method was done by characterization of chitosan milispheres and liposomes entrapping Zanthoxylum tingoassuiba essential oil, which contains appreciable amount of (−)‐α‐bisabolol. A reversed‐phase C₁₈ column and gradient elution was used with the mobile phase composed of (A) acetonitrile–water–phosphoric acid (19:80:1) and (B) acetonitrile. The eluent was pumped at a flow rate of 0.8 mL/min with UV detection at 200 nm. In the range 0.02–0.64 mg/mL the assay showed good linearity (R² = 0.9999) and specificity for successful identification and quantitation of (−)‐α‐bisabolol in the essential oil without interfering peaks. The method also showed good reproducibility, demonstrating inter‐day and intra‐day precision based on relative standard deviation values (up to 3.03%), accuracy (mean recovery of 100.69% ± 1.05%) and low values of detection and quantitation limits (0.0005 and 0.0016 mg/mL, respectively). The method was also robust for showing a recovery of 98.81% under a change of solvent in standard solutions. The suitability of the method was demonstrated by the successful determination of association efficiency of the (−)‐α‐bisabolol in chitosan milispheres and liposomes. Copyright © 2009 John Wiley & Sons, Ltd.     

Further Alkaloids from the Leaves of Trigonostemon lii

Four new indole alkaloids, trigonoliimines D–G ( 1 – 4 , resp.), were isolated from Trigonostemon lii. Their structures were elucidated by spectroscopic methods, including extensive 1D‐ and 2D‐NMR experiments.     

A New Megastigmane Palmitate and a New Oleanane Triterpenoid from Aster yomena Makino

A new megastigmane palmitate, 9‐oxomegastigm‐5(13)‐ene‐2β‐palmitate ( 1 ), and a new oleanane triterpenoid, (3β)‐3,23,28‐trihydroxyolean‐12‐en‐11‐one ( 2 ), together with three known oleanane‐type triterpenoids, β‐amyrin ( 3 ), erythrodiol ( 4 ), and (3β)‐olean‐12‐ene‐3,23,28‐triol ( 5 ), were isolated from the aerial parts of Aster yomena (Asteraceae). Their structures were identified based on 1D‐ and 2D‐NMR analysis, including ¹H,¹H‐COSY, HSQC, HMBC, and NOESY techniques.