C5–C10 Directly Bonded Tetrodotoxin Analogues: Possible Biosynthetic Precursors of Tetrodotoxin From Newts

The identification of novel tetrodotoxin (TTX, 1 ) analogues would significantly contribute to the elucidation of its biosynthetic pathway. In this study, the first C5–C10 directly bonded TTX analogues, 4,9‐anhydro‐10‐hemiketal‐5‐deoxyTTX ( 2 ) and 4,9‐anhydro‐8‐epi‐10‐hemiketal‐5,6,11‐trideoxyTTX ( 3 ), were found in the newt Cynops ensicauda popei by using a screening method involving HILIC‐LC–MS/MS focused on the fragment ions of TTX analogues, and their structures were elucidated by spectroscopic methods. Compound 2 was detected in a wide range of newt species, and the 2 and TTX contents of 22 newt specimens were correlated (r_s=0.88). Based on these results and its structural features, 2 was predicted to serve as a precursor of TTX that would be directly converted into 4,9‐anhydroTTX ( 4 ) by Baeyer–Villiger‐like oxidation or via 4,9‐anhydro‐5‐deoxyTTX formed by cleavage of the C5–C10 bond. The bicyclic carbon skeletons of 2 and 3 suggested a possible monoterpene origin for TTX.     

Sarcaglarols A—D,Lindenane−Monoterpene Heterodimers from Sarcandra glabra Based on Molecular Networks

Sarcaglarols A—D ( 1 — 4 ), two pairs of lindenane?monoterpene heterodimers fused by a 1,2‐dioxane moiety, were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking‐based strategy. Their planar structures, absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS, NMR spectroscopic data, ECD spectrum, and the X‐ray diffraction study of isopropylidene derivatives. An intermolecular [2+2+2] cycloaddition may play a key role in the biosynthesis pathway of the 1,2‐dioxane moiety fused lindenane?monoterpene heterodimer skeleton, which can be recognized as the biogenetic precursors of our previous reported lindenane?normonoterpene conjugates. In addition, compounds 1 , 3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid‐exposed L02 cells.     

Two New Sesquiterpenes from Euonymus alatus

Two new sesquiterpenes, 1 and 2 , as well as the five known compounds 3 – 7 , were isolated from the stems of Euonymus alatus. Compounds 2 – 7 have a β‐dihydroagarofuran skeleton. The structures of these compounds were elucidated mainly by spectroscopic methods (1D‐, 2D‐NMR, ESI‐MS, and HR‐ESI‐MS). We also report the X‐ray crystal structure of evonine ( 3 ) for the first time.     

Baeckeins J and K,Two Novel C‐Methylated Biflavonoids from the Roots of Baeckea frutescens and Their Cytoprotective Activities

Baeckea frutescens is an aromatic shrub used as ornamentals and as food flavor spices in the southern part of P. R. China. Two novel C‐methylated biflavonoids named baeckeins J ( 1 ) and K ( 2 ) were isolated from the roots of B. frutescens, which possessed the unique carbon skeleton conjugated of a flavonol and one isoflavanonol molecule via the linkages of C(2)–C(8*) and C(3)–O–C(7*). The structures of compounds 1 and 2 were elucidated by analysis of 1D‐ and 2D‐NMR, and HR‐ESI‐MS spectral data, and the absolute configuration for chiral C‐atoms C(2) and C(3) were assigned by CD spectrometry combined with quantum chemical calculations. In the bioassay, baeckeins J and K exhibited strong cytoprotective effects on H₂O₂‐induced oxidative cell death in PC12 cells.     

Chloropupukeanolides C-E: cytotoxic pupukeanane chlorides with a spiroketal skeleton from Pestalotiopsis fici

Chloropupukeanolides C–E ( 8 – 10 ), three highly functionalized secondary metabolites featuring a novel spiroketal skeleton derived from the chlorinated tricyclo‐[4.3.1.0^{3, 7}]‐decane (pupukeanane) and the 2,6‐dihydroxy‐4‐methylbenzoic acid moieties, were isolated from the scale‐up fermentation extract of the plant endophytic fungus Pestalotiopsis fici. The constitutions of compounds 8 – 10 were elucidated primarily by NMR experiments. Their relative configurations were deduced by analogy to metabolites 4 – 6 , which were previously isolated from the same fungus. The absolute configuration of 8 was assigned by X‐ray crystallography and those of 9 and 10 by quantum‐chemical CD calculations. Biogenetically, chloropupukeanolides C–E ( 8 – 10 ) are presumably derived from the same oxidation‐induced Diels–Alder reaction pathway as compounds 1 and 4 – 7 , via the putative biosynthetic precursors 2 and 3 . The opposite configurations of the complete “Southern parts” of 8 and 9 suggests that this Diels–Alder reaction is stereochemically not very selective. Compounds 8 – 10 showed significant cytotoxicity against a small panel of human tumor cell lines and weak activities against the pathogens of tropical diseases.     

Hemsleyaconitines F and G,Two Novel C19‐Diterpenoid Alkaloids Possessing a Unique Skeleton from Aconitum hemsleyanum

Hemsleyaconitines F and G ( 1 and 2 , resp.) were isolated from the EtOH extract of Aconitum hemsleyanum. Their structures were elucidated by extensive analyses of the IR, 1D‐ and 2D‐NMR, and MS data. The two C₁₉‐diterpenoid alkaloids 1 and 2 possess a novel skeleton, featuring a five‐membered D‐ring between C(9), C(13), C(14), C(15), and C(16), which is quite different from the previously isolated six‐membered D‐ring analogs.     

Three New Monoterpene Alkaloids and a New Caffeic Acid Ester from Incarvillea mairei var. multifoliolata

Three new monoterpene alkaloids, mairine A ( 1 ), mairine B ( 2 ), and mairine C ( 3 ), and a new caffeic acid ester, 2‐(1‐hydroxy‐4,4‐dimethoxycyclohexyl)ethyl caffeate ( 4 ), were isolated from the EtOH extract of the whole plants of Incarvillea mairei var. multifoliolata. The structures of these compounds were established on the basis of 1D‐ and 2D‐NMR and HR‐ESI‐MS analysis.     

Chromenone Glucosides Acylated with Monoterpene Acids from the Leaves of Eucalyptus camaldulensis var. obtusa

Three new chromenone glucosides acylated with monoterpene acids, eucamaldusides A ( 1 ), B ( 2 ), and C ( 3 ), were isolated from the leaves of Eucalyptus camaldulensis var. obtusa, together with the five known compounds ursolic acid lactone, obtusilin, β‐sitosterol glucoside, 4‐hydroxybenzoic acid, and cypellocarpin C. The structures of the new compounds were established by exhaustive 1D‐ and 2D‐NMR spectroscopic studies. Their configuration was determined by measuring the [α]_D of the known methyl esters of the monoterpene acids obtained by methanolysis of 1 – 3 .     

A New Cyclic Peptide and a New Steroid from the Fungus Penicillium sp. GD6 Isolated from the Mangrove Bruguiera gymnorrhiza

A rare new cyclic tetrapeptide, 5,5′‐epoxy‐MKN‐349A ( 1 ), featured by a MKN‐349A ( 5 ) skeleton and containing an uncommon ether bridge between C(5) and C(5′), and a new steroid, named 11‐O‐acetyl‐NGA0187 ( 2 ), together with two known steroids, 3 and 4 , were isolated from an endophytic fungus Penicillium sp. GD6 associated with the Chinese mangrove Bruguiera gymnorrhiza. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and by comparison with the data of related compounds reported in literature. Neither of the compounds 3 and 4 , isolated in this study, showed obvious bioactivities in the antibacterial bioassay experiments.     

Two Novel Monoterpene Alkaloid Dimers from Incarvillea arguta

Two novel monoterpene alkaloid dimers, named argutanes A and B ( 1 and 2 , resp.), together with the known alkaloid boschniakine ( 3 ), were isolated from the roots of Incarvillea arguta. The structures were elucidated on the basis of 1D‐ and 2D‐NMR, as well as HR‐ESI‐MS data.     

Transition Metal Acetate Promoted Syntheses of Some New N‐Heterocycles by Multicomponent Reactions

The intermolecular cyclization reactions of N‐tosyl‐ethylenediamine with glyoxal promoted by transition metal acetate at different ratios gave three N‐heterocyclic compounds. The ligand in compound 1 contains one N‐heterocycle, which is formed by a one‐pot three‐component reaction. In compound 2 , two imidazolidine rings and one piperazine ring are fused together to form a tricyclic skeleton by a one‐pot five‐component reaction. Two 1,3,6‐triazabicyclo[3.3.0]octanes are connected by one C–C bond to form the skeleton of 3 , which is constructed from a one‐pot nine‐component reaction. It revealed that the key factor for the preparation of these compounds is the ratio of starting materials, as well as the presence of corresponding transition metal acetates.     

Three New E‐Secoursane Triterpenoid Saponins from the Leaves of Ilex dunniana

Three new triterpenoid saponins with an 18,19‐secours‐13(18)‐ene skeleton, dunnianaolactones A–C ( 1 – 3 , resp.), together with nine known compounds i.e., the ursane‐type triterpene saponin 4 , the two benzofuran lignans 5 and 6 , five flavonoid glycosides, and 4‐hydroxybenzoic acid, were isolated from the leaves of Ilex dunniana Levl . (Aquifoliaceae). Their structures were elucidated by means of spectroscopic and chemical methods. The configuration of dunnianaolactone A ( 1 ) was further confirmed by X‐ray crystal‐structure analysis.     

Isolation and Structural Characterization of New,Highly Functionalized Diterpenes from Euphorbia serrulata

Five new diterpene polyesters, 1 – 5 , with jatrophane skeletons were isolated from the fresh whole plants of Euphorbia serrulata. The structure elucidation was performed by means of UV/VIS spectroscopy, HR‐ESI‐MS, and advanced two‐dimensional NMR methods, including ¹H‐NMR, JMOD, ¹H,¹H‐COSY, NOESY, HMQC, and HMBC experiments. The relative configurations of 1 – 5 and their conformations in solution were analyzed on the basis of NOESY measurements. As a result of detailed NMR studies, complete ¹H and ¹³C chemical‐shift assignments of the compounds were possible. The isolated compounds differ stereochemically and do not comprise a uniform series regarding the configurations at C(2), C(6), and C(13). Compound 5 possesses the new structural feature of a double bond with (Z)‐configuration in the macrocyclic ring of the jatrophane skeleton, while compound 2 has a C?C bond in the five‐membered ring, this being the first observation of this structural feature in the type of macrocyclic Euphorbiaceae diterpenes.     

A Facile One Pot Synthesis of New Tricyclic Coumarins from Single Synthon [1

A high yielding method for the synthesis of new tricyclic coumarins is reported herein using 8‐formyl‐7‐hydroxy‐4‐methyl coumarin as a single synthon. Different strategies were employed to synthesize tricyclic coumarins fused with isoxazole and pyran at C7‐C8 position in the coumarin skeleton. Functional group modifications during the construction of pyrazolyl coumarin has resulted in novel oxidative ipso nitration. The O‐tosylate was subjected to conditions of pressure in a sealed tube experiment, since it was not possible to replace the 7‐hydroxy group of coumarin by regular methods. All the compounds synthesized during the present investigation were characterized by IR, ¹H‐NMR, ¹³C‐NMR, ESI‐MS, and elemental analysis. The X‐ray diffraction data of some of the intermediate hydrazones are also reported herein.     

The Synthesis,Spectral, and Electrochemical Characterization of Novel Alkoxybenzoquinone Derivatives

The novel monosubstituted benzoquinone compounds 3e , 3g , 3h ; 2,5‐O‐ substituted benzoquinone compounds 4a , 4b , 4c , 4d , 4e 4g and known compound 4h and 2,6‐O‐ substituted benzoquinone compounds 5e , 5f , 5g , 5h were obtained by the reaction of p‐chloranil ( 1 ) and related alcohol compounds in potassium carbonate (K₂CO₃) solution of acetonitrile or chloroform with Et₃N. The novel cyclic compounds 7 , 8 and 10 , 11 were obtained from the reaction of p‐chloranil ( 1 ) and diols in potassium carbonate (K₂CO₃) solution of acetonitrile at room temperature. The structures of novel compounds were characterized by using micro analysis, FT‐IR, ¹H‐NMR, ¹³C‐NMR, MS and cyclic voltammetry.     

Screening,separation, and evaluation of xanthine oxidase inhibitors from Paeonia lactiflora using chromatography combined with a multi‐mode microplate reader

Natural products have become one of the most important resources for discovering novel xanthine oxidase inhibitors, which are commonly employed in the treatment of hyperuricemia and gout. However, to date, few reports exist regarding the use of monoterpene glycosides as xanthine oxidase inhibitors. Thus, we herein report the use of ultrafiltration coupled with liquid chromatography in the screening of monoterpene glycoside xanthine oxidase inhibitors from the extract of Paeonia lactiflora (P. lactiflora ), and both high‐performance counter‐current chromatography and medium‐pressure liquid chromatography were employed to separate the main constituents. Furthermore, the xanthine oxidase inhibitory activities and the mechanisms of inhibition of the isolated compounds were evaluated using a multi‐mode microplate reader by Molecular Devices. As a result, three monoterpene glycosides were separated by combined high‐performance counter‐current chromatography and medium‐pressure liquid chromatography in purities of 90.4, 98.0, and 86.3%, as determined by liquid chromatography. These three compounds were identified as albiflorin, paeoniflorin, and 1‐O‐β‐ᴅ‐glucopyranosyl‐8‐O‐benzoylpaeonisuffrone by electrospray ionization tandem mass spectrometry, and albiflorin and paeoniflorin were screened as potential xanthine oxidase inhibitors by ultrafiltration with liquid chromatography. The evaluation results of xanthine oxidase inhibitory activity corresponded with the screening results, as only albiflorin and paeoniflorin exhibited xanthine oxidase inhibitory activity.     

Access to nonisocyanate poly(thio)urethanes: A comparative study

This article describes the synthesis of new cyclic compounds able to react with amines to get nonisocyanate polyurethanes (NIPUs). The contribution of the most studied five‐membered cyclic carbonate was compared to five‐membered cyclic dithiocarbonate analogous and to a six‐membered cyclic carbonate. Difunctional reactive species were obtained by a simple substitution reaction or an efficient thiol–ene coupling reaction. The products, obtained with high yields, were characterized by 1H NMR, 13C NMR, and Fourier tansform infrared spectroscopy analysis. The dicyclocarbonates were then used to synthesize NIPUs by step growth polymerization with several diamines. These materials exhibited glass transition temperatures from 19 to ?29 °C, molar mass from 1800 to 20,400 g mol^?1, and a 20% mass loss temperature (T_d = 20%) between 249 and 296 °C. Such materials are interesting candidates for coating applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3284–3296     

Baeckeins A and B,Two Novel 6‐Methylflavonoids from the Roots of Baeckea frutescens

A pair of novel isomeric 6‐methylflavonoids, named baeckeins A ( 1 ) and B ( 2 ), were isolated from the roots of Baeckea frutescens. The two compounds possess a unique C₂₃ skeleton, resulting from the 6‐methylation and 8‐arylation of a flavonol (=3‐hydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one) framework and the formation of an unusual lactone ring E. Their structures were elucidated by detailed spectroscopic analyses, including HR‐ESI‐MS and 1D‐ and 2D‐NMR data (HSQC, HMBC, and ROESY). A plausible biogenetic pathway for compounds 1 and 2 is also proposed (Scheme).     

Annosqualine: a Novel Alkaloid from the Stems of Annona squamosa

Annosqualine (=(10′bR)‐1′,5′,6′,10′b‐tetrahydro‐9′‐hydroxy‐7′,8′‐dimethoxyspiro[cyclohexa‐2,5‐diene‐1,2′‐pyrrolo[2,1‐a]isoquinoline]‐3′,4‐dione; 1 ), a novel alkaloid with an unprecedented skeleton, and a new amide, dihydrosinapoyltyramine (=3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐N‐[2‐(4‐hydroxyphenyl)ethyl]propanamide; 2 ), were isolated from the stems of Annona squamosa L., together with six known alkaloids. The structures of all compounds were elucidated spectroscopically by means of optical rotation, ¹H‐, ¹³C‐, and 2D‐NMR, and by EI‐MS, or by comparison with the spectral data of authentic samples. A possible biogenetical pathway towards annosqualine ( 1 ) is proposed.     

Three New Bisabolocurcumin Ethers from the Rhizomes of Curcuma longa L.

Three new bisabolocurcumin ethers, named demethoxybisabolocurcumin ether ( 1 ), bisabolocurcumin ether ( 2 ), and didemethoxybisabolocurcumin ether ( 3 ), along with two known compounds, 4 and 5 , were isolated from the AcOEt extract of the rhizomes of Curcuma longa L. Their structures were established by the analysis of NMR and MS data. The new compounds 1 – 3 , which possess a new 1,7‐diarylheptanoid skeleton linked with a bisabolone‐type sesquiterpene substructure by a C? O bond, were found for the first time in a natural source.