Terpenoids from Two Dicranopteris Species

Two new compounds, (6S,13S)‐6‐{[β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}cleroda‐3,14‐dien‐13‐ol ( 1 ) and kadsuric acid 3‐methyl ester ( 2 ), together with nine known compounds, (6S,13E)‐6‐{[β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}cleroda‐3,13‐dien‐15‐ol ( 3 ), (6S,13S)‐6‐[6‐O‐acetyl‐β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}‐13‐{[α‐L ‐rhamnopyranosyl‐(1→4)‐β‐D ‐fucopyranosyl]oxy}cleroda‐3,14‐diene ( 4 ), (6S,13S)‐6‐{[6‐O‐β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}‐13‐{[α‐L ‐rhamnopyranosyl‐(1→4)‐β‐D ‐fucopyranosyl]oxy}cleroda‐3,14‐diene ( 5 ), 15‐hydroxydehydroabietic acid ( 6 ), 15‐hydroxylabd‐8(17)‐en‐19‐oic acid ( 7 ), junicedric acid ( 8 ), (4β)‐kaur‐16‐en‐18‐oic acid ( 9 ), (4β)‐16‐hydroxykauran‐18‐oic acid ( 10 ), and (4β,16β)‐16‐hydroxykauran‐18‐oic acid ( 11 ) were isolated from the fronds of Dicranopteris linearis or D. ampla. Their structures were established by extensive 1D‐ and 2D‐NMR spectroscopy. Compounds 1 and 3 – 8 showed no anti‐HIV activities.     

Thrombin Inhibitory Constituents from Duranta repens

The C‐alkylated flavonoids 3,7,4′‐trihydroxy‐3′‐(4‐hydroxy‐3‐methylbutyl)‐5,6‐dimethoxyflavone ( 1 ), 3,7‐dihydroxy‐3′‐(4‐hydroxy‐3‐methylbutyl)‐5,6,4′‐trimethoxyflavone ( 2 ) and the trans‐clerodane diterpenoids 6β‐hydroxy‐15,16‐epoxy‐5β,8β,9β,10α‐cleroda‐3,13(16),14‐trien‐18‐oic acid ( 3 ) and 2β‐hydroxy‐15,16‐epoxy‐5β,8β,9β,10α‐cleroda‐3,13(16),14‐trien‐18‐oic acid ( 4 ) were isolated from Duranta repens. Their structures and the relative configuration of 3 and 4 were determined by spectroscopic methods (¹H‐ and ¹³C‐NMR, IR, and MS) and 2D‐NMR experiments. The known flavonoid 5 is also reported for the first time from this species. The compounds 1 , 3 , and 5 showed significant enzyme‐inhibitory activity against thrombin.     

Three New Clerodane Diterpenoids from the Bulbils of Dioscorea bulbifera L. var. sativa

From the bulbils of Dioscorea bulbifera L. var. sativa, three new clerodane diterpenoids, bafoudiosbulbin C (=methyl (2β,8α,12S)‐17‐oxo‐2,19 : 8,19 : 12,17 : 15,16‐tetraepoxycleroda‐3,13(16), 14‐triene‐18‐carboxylate; 1 ), bafoudiosbulbin D (=methyl (2β,6β,12R)‐17,19‐dioxo‐2,19 : 6,17 : 8,12 : 15,16‐tetraepoxycleroda‐13(16),14‐diene‐18‐carboxylate; 2 ), and bafoudiosbulbin E (=methyl (2β,3α,4α,6β,12R)‐17,19‐dioxo‐2,19 : 3,4 : 6,17 : 8,12 : 15,16‐pentaepoxycleroda‐13(16),14‐diene‐18‐carboxylate; 3 ) were isolated, together with the known compounds bafoudiosbulbins A and B, 3‐O‐β‐D ‐glucopyranosyl‐β‐sitosterol, and 6′‐stearoyl‐3‐O‐β‐D ‐glucopyranosyl‐β‐sitosterol. Their structures were established by high‐field NMR techniques (¹H,¹H‐COSY, ¹³C‐DEPT, HSQC, HMBC, and NOESY), MS analyses, as well as by comparison of their spectral data with those of related compounds.     

Two New Labdane‐Type Diterpene Acids from the Wood of Cunninghamia konishii

Two new labdane‐type diterpene acids, (12S)‐12‐hydroxylabda‐8(17),13(16),14‐trien‐18‐oic acid ( 1 ) and (12R)‐12‐hydroxy‐15,16‐epoxylabda‐8(17),13‐dien‐18‐oic acid ( 2 ), along with a known labdane‐type diterpene, (11E)‐15,16‐bisnor‐13‐oxolabda‐8(17),11‐dien‐19‐oic acid ( 3 ), were isolated from the MeOH extract of the wood of Cunninghamia konishii. Their structures were determined by analysis of spectroscopic data and comparison with the data of known analogs.     

Tocopherols and Triterpenoids from Sida acuta

A new tocopherol derivative, 7_a‐methoxy‐α‐tocopherol ( 1 ), and a new taraxastane triterpene, taraxast‐1,20(30)‐dien‐3‐one ( 5 ), together with four known compounds, β‐tocopherol ( 2 ), α‐tocopherol ( 3 ), α‐tocospiro B ( 4 ) and taraxasterone ( 6 ) were isolated from the whole plant of Sida acuta. Their structures were elucidated by spectral analysis including MS, 1D and 2D‐NMR spectroscopy. Among those compounds, compounds 1 , 2 , and 3 showed significant antioxidant effect (EC₅₀ = 86.9, 68.2, and 70.9 μM, respectively) in the DPPH radicals scavenging activity assay.     

Diterpene Glycosides from the Dry Fronds of Conyza japonica

Phytochemical investigation of the 95% EtOH extract of the dry fronds of Conyza japonica (Thunb .) Less. resulted in the isolation of three new labdane diterpene glycosides, (3β,13S)‐13‐O‐α‐L ‐rhamnopyranosyllabda‐8(17),14‐dien‐3‐yl α‐L ‐rhamnopyranoside ( 1 ), (3β,13S)‐13‐O‐α‐L ‐rhamnopyranosyllabda‐8(17),14‐diene‐3‐yl 2‐O‐acetyl‐α‐L ‐rhamnopyranoside ( 2 ), and (3β,13S)‐13‐O‐α‐L ‐rhamnopyranosylabda‐8(17),14‐dien‐3‐yl 6‐O‐acetyl‐β‐D ‐glucopyranosyl‐(1→2)‐α‐L ‐rhamnopyranoside ( 3 ), together with their aglycone, (13S)‐labda‐8(17),14‐diene‐3,13‐diol ( 4 ). Their structures were characterized by spectroscopic analyses and chemical correlations, including 1D‐ and 2D‐NMR, and HR‐ESI‐MS. Furthermore, compounds 1 – 3 appeared to be promising as active agents against the tested pathogen fungi and oral pathogens as they possessed moderate cytotoxic properties.     

Neoclerodane Diterpenes from Amoora stellato‐squamosa

From the twigs of Amoora stellato‐squamosa, five new neoclerodane diterpenes have been isolated and characterized, methyl (13E)‐2‐oxoneocleroda‐3,13‐dien‐15‐oate (=methyl (2E)‐3‐methyl‐5‐[(1S,2R,4aR,8aR)‐1,2,3,4,4a,7,8,8a‐octahydro‐1,2,4a,5‐tetramethyl‐7‐oxo‐naphthalen‐1‐yl]pent‐2‐enoate; 1 ), (13E)‐2‐oxoneocleroda‐3,13‐dien‐15‐ol (=(4aR,7R,8S,8aR)‐1,2,4a,5,6,7,8,8a‐octahydro‐8‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐4,4a,7,8‐tetramethylnaphthalen‐2(1H)‐one; 2 ), (3α,4β,13E)‐neoclerod‐13‐ene‐3,4,15‐triol (=(1R,2R,4aR, 5S,6R,8aR)‐decahydro‐5‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalene‐1,2‐diol; 3 ), (3α,4β,13E)‐4‐ethoxyneoclerod‐13‐ene‐3,15‐diol (=(1R,2R,4aR,5S,6R,8aR)‐1‐ethoxydecahydro‐5‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalen‐2‐ol; 4 ), and (3α,4β,14RS)‐neoclerod‐13(16)‐ ene‐3,4,14,15‐tetrol (=(1R,2R,4aR,5S,6R,8aR)‐decahydro‐5‐[3‐(1,2‐dihydroxyethyl)but‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalene‐1,2‐diol; 5 ), together with two known compounds, (13E)‐neocleroda‐3,13‐diene‐15,18‐diol ( 6 ) and (13S)‐2‐oxoneocleroda‐3,14‐dien‐13‐ol ( 7 ).     

Two New Tetracyclic Triterpenoids and Other Constituents from Aster Ageratoides var. Oophyllus

Two new tetracyclic triterpenoids shiona‐19(E),21‐dien‐3β‐ol ( 1 ), and shiona‐22(29)‐en‐3β,21‐diol ( 2 ), together with four known compounds shiona‐21‐en‐3β‐ol ( 3 ), friedelinol ( 4 ), β‐sitosterol ( 5 ), and (24R)‐stigmast‐7,22(E)‐dien‐3a‐ol ( 6 ) were isolated from Aster ageratoides var. oophyllus. The structures of two new compounds were established on the basis of IR, MS, ¹H, ¹³C and 2D NMR spectroscopic methods.     

Simultaneous estimation of 16α-hydroxycleroda-3,13(14) Z-dien-15,16-olide from Polyalthia longifolia and its metabolite in hamster plasma: application to pharmacokinetic study

A selective and sensitive LC–MS‐MS method was developed and validated for simultaneous estimation and pharmacokinetic studies of 16α‐hydroxycleroda‐3,13(14) Z‐dien‐15,16‐olide (K‐09) obtained from Polyalthia longifolia and its metabolite (K‐9T), a novel antidyslipidemic agent. Sample clean‐up involved liquid–liquid extraction of both the analytes and internal standard (rosuvastatin) from 200 μL of hamster plasma. The analytes were chromatographically separated on a Symmetry‐Shield C₁₈ (5 µm, 4.6 × 150 mm) column, using acetonitrile–0.1% aqueous formic acid (92:08, v/v) as the mobile phase. Detection was performed using negative ion electrospray ionization in multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 1.56–200 ng/mL, with a correlation coefficient (r²) of 0.998 or better. The within‐ and between‐batch precisions (relative standard deviation, %RSD) and the accuracy (percentage bias) were within acceptable limits as per FDA guidelines. The validated method was successfully applied to reveal the pharmacokinetic parameters of K‐09 and metabolite after oral administration. This method will therefore be highly useful for future studies of K‐09 and metabolite K‐9T pharmacokinetics in preclinical and clinical studies. Copyright © 2011 John Wiley & Sons, Ltd.     

The Constituents of Lindera Glauca

Twenty‐eight compounds including seven alkaloids, (+)‐3‐chloro‐N‐formylnornantenine ( 1 ), (+)‐N‐formylnornantenine ( 2 ), (+)‐boldine ( 3 ), (+)‐norboldine ( 4 ), (‐)‐norboldine ( 5 ), lycicamine ( 6 ), and tetrahydroberberine ( 7 ); four flavonoids, kaempferol ( 8 ), kaempferol‐3‐O‐arabinoside ( 9 ), quercetin ( 10 ), and quercetin‐3‐O‐rhamnoside ( 11 ); one butanolide, akolactone A ( 12 ); one p‐quinone, 2,6‐dimethoxy‐p‐quinone ( 13 ); one cyclohex‐2‐en‐1‐one, blumenol A ( 14 ); six benzenoids, methylparaben ( 15 ), p‐hydroxybenzoic acid ( 16 ), vanillic acid ( 17 ), syringic acid ( 18 ), 3,4,5‐trimethoxybenzoic acid ( 19 ), and 3‐(3,4‐dihydroxyphenyl) propionic acid ( 20 ); one diterpene, phytol ( 21 ); one triterpene, squalene ( 22 ); six steroids, (3‐sitosterol ( 23 ), β‐sitostenone ( 24 ), stigmasta‐4,22‐dien‐3‐one ( 25 ), 6β‐hydroxy‐β‐sitostenone ( 26 ), 6β‐hydroxystigmasterone ( 27 ), and β‐sitosteryl‐D‐glucoside ( 28 ) were isolated from the aerial part of Lindera glauca. These compounds were characterized and identified by physical and spectral method. All compounds were isolated for the first time from this plant. Among them, (+)‐3‐chloro‐N‐formylnornantenine ( 1 ) is a new one.     

Three Novel Triterpenoid Dienolides from Phyllanthus myrtifolius

Three novel pentacyclic triterpenoid dienolides, phyllenolide A (=3β‐acetoxyglutina‐5(10), 6‐dien‐27,8α‐olide; 1 ), phyllenolide B (=3β‐(benzoyloxy)glutina‐5(10),6‐dien‐27,8α‐olide; 2 ), and phyllenolide C (=3β‐(2‐hydroxybenzoyloxy)glutina‐5(10),6‐dien‐27,8α‐olide; 3 ), were isolated from the aerial parts of Phyllanthus myrtifolius Moon . (Euphorbiaceae). These three compounds possess an endocyclic γ‐lactone moiety across ring C and a homo‐annular diene system in ring B. Their structures were established by analyses of CD, NOED, and 2D‐NMR spectra.     

Cucurbitane Triterpenoids from the Fruit Pulp of Momordica charantia and Their Cytotoxic Activity

Two new cucurbitane‐type triterpenes, 25‐methoxycucurbita‐5,23(E)‐diene‐3β,19‐diol ( 1 ) and 7β‐ethoxy‐3β‐hydroxy‐25‐methoxycucurbita‐5,23(E)‐dien‐19‐al ( 2 ), together with three known cucurbitane‐type triterpenes, 3β,7β,25‐trihydroxycucurbita‐5,23(E)‐dien‐19‐al ( 3 ), (23E)‐3β‐hydroxy‐7β,25‐dimethoxycucurbita‐5,23‐dien‐19‐al ( 4 ), and 3β‐hydroxy‐25‐methoxycucurbita‐6,23(E)‐dien‐19,5β‐olide ( 5 ), were isolated from the fruit pulp of Momordica charantia. The structures of two new compounds were elucidated on the basis of 1D and 2D NMR, MS, IR, optical rotation. Among these isolates, compounds 1 , 2 , and 5 showed slight cytotoxic activity against the SK‐Hep 1 cell line with IC₅₀ values of 33.1, 24.3, and 38.7 μM, respectively.     

Baimantuoluosides A – C,Three New Withanolide Glucosides from the Flower of Datura metel L.

In search for bioactive compounds from the flower of Datura metel L., three new withanolide glucosides, namely baimantuoluosides A, B, and C ( 1 – 3 , resp.) were isolated. Enzymatic hydrolysis of 1 – 3 afforded the corresponding aglycones 1a, 2a , and 3a , respectively. The structures of the new compounds were elucidated as (5α,6α,7α,12β,22R)‐5,12‐dihydroxy‐1,26‐dioxo‐6,7 : 22,26‐diepoxyergosta‐2,24‐dien‐27‐yl β‐D ‐glucopyranoside ( 1 ), (5α,6α,7α,12α,22R)‐5,12‐dihydroxy‐1,26‐dioxo‐6,7 : 22,26‐diepoxyergosta‐2,24‐dien‐27‐yl β‐D ‐glucopyranoside ( 2 ), (5α,6α,7α,22R)‐5‐hydroxy‐1,26‐dioxo‐6,7 : 22,26‐diepoxyergosta‐2,24‐dien‐27‐yl β‐D ‐glucopyranoside ( 3 ) on the basis of chemical and physicochemical evidence, and are further confirmed by the structure determination by X‐ray diffraction of withanolide aglycone 1a .     

Chemical Constituents of Acanthochlamys bracteata

A novel nortriterpene, acanthochlamic acid (6), along with 18 known compounds has been isolated from the whole plants of Acanthochlamys bracteata P. C. Kao, a single species in family Acanthochlamydaceae which is endemic to the southwest of China. The structure of the novel nortriterpene was elucidated as 3,4-seco-3-norlup-4(23),20(29)-dien-2,28-dioic acid by spectroscopic techniques including 1D and 2D NMR spectroscopy and confirmed by X-ray crystallography.     

New ent‐Pimarane Diterpenes from the Roots of Aralia dumetorum

Four new ent‐pimarane diterpenes were isolated from the EtOH extract of Aralia dumetorum, together with three known compounds involving ent‐pimar‐8(14),15‐dien‐19‐oic acid ( 5 ), ent‐pimar‐8(14),15‐dien‐19‐ol ( 6 ), and ent‐kaur‐16‐en‐19‐oic acid ( 7 ). By detailed analyses of the MS, IR, and NMR data, the structures of four new diterpenes were characterized as (5β,9β,10α,13α)‐pimara‐6,8(14),15‐trien‐18‐oic acid ( 1 ), (5β,7β,9β,10α,13α)‐7‐methoxypimara‐8(14),15‐dien‐18‐oic acid ( 2 ), (5β,9β,10α,13α,14β)‐14‐methoxypimara‐7,15‐dien‐18‐oic acid ( 3 ), and (5β,10α,13α,14α)‐14‐hydroxypimara‐7,9(11),15‐trien‐18‐oic acid ( 4 ). The cytotoxic activities of compounds 1  –  7 were assayed in vitro through MTT method.     

Triterpenoids and other Constituents from Euphorbia Humifusa

A novel lupane‐type triterpenoid, 3,4‐seco‐lupa‐4(23), 20(29)‐dien‐24‐hydroxy‐3‐oic acid (1) and a new cycloartane‐type triterpenoid, 23(E)‐cycloart‐23‐en‐25‐ethoxy‐3β‐ol (7), as well as eighteen known compounds, were isolated from the hot ethanol extract of the whole plant of Euphorbia humifusa Willd. The new structures were characterized by means of spectroscopic methods including 1D, 2D NMR and HRESIMS, and the known ones were established on the basis of comparing their NMR data with those of the corresponding compounds in the literature. In addition, cytotoxicity against selected cancer cell human gastric carcinoma (SGC‐7901) of compounds 1,3,4,6 were measured in vitro.     

Sesquiterpenoids and Phenylpropane Derivatives from Sonchus uliginosus

Six new compounds were isolated from the whole plant of Sonchus uliginosus, including three eudesmane‐type sesquiterpenoids (1β,6α)‐1,6,14‐trihydroxyeudesm‐3‐en‐12‐oic acid γ‐lactone ( 1 ), (1β,6α)‐1,6,14‐trihydroxyeudesma‐3,11(13)‐dien‐12‐oic acid γ‐lactone ( 2 ), and (1β,6α)‐1,6‐dihydroxy‐14‐O‐[(4‐hydroxyphenyl)acetyl]eudesma‐3,11(13)‐dien‐12‐oic acid γ‐lactone ( 3 ), and three phenylpropane derivatives, 4‐hydroxy‐γ,3,5‐trimethoxybenzenepropanol ( 6 ), γ,3,4,5‐tetramethoxybenzenepropanol ( 7 ), and γ,3,4,5‐tetramethoxybenzenepropanol acetate ( 8 ), together with the two known compounds 4 and 5 . The new structures were elucidated by means of spectroscopic methods, such as IR, EI‐MS, HR‐ESI‐MS, 1D‐ and 2D‐NMR, and by comparison of the spectroscopic data with those reported for structurally related compounds.     

Cucurbitane‐Type Triterpenoids from Momordica charantia

The six new cucurbitane‐type triterpenoids 1 – 6 , along with the ten known triterpenoids 7 – 16 , were isolated from the vines and leaves of Momordica charantia. The structures of the new compounds were elucidated as (3β,7β,15β,23E)‐3,7,15,25‐tetrahydroxycucurbita‐5,23‐dien‐19‐al ( 1 ), (3β,7β)‐3,7,22,23‐tetrahydroxycucurbita‐5,24‐dien‐19‐al ( 2 ), (3β,7β)‐3,7,23,24‐tetrahydroxycucurbita‐5,25‐dien‐19‐al ( 3 ), (3β,7β,23S)‐3,7,23‐trihydroxycucurbita‐5,24‐dien‐19‐al 7‐β‐D ‐glucopyranoside ( 4 ), (3β,7β,23E)‐cucurbita‐5,23‐diene‐3,7,19,25‐tetrol 7‐β‐D ‐glucopyranoside ( 5 ), and (3β,7β,23E)‐3,7‐dihydroxy‐25‐methoxy‐cucurbita‐5,23‐dien‐19‐al 3‐β‐D ‐allopyranoside ( 6 ), by extensive analyses of their spectral data, as well as by chemical methods.     

Five New Eremophilane Sesquiterpenes from Ligularia przewalskii

Five new eremophilane‐type sesquiterpenes, 3β‐(acetyloxy)‐7‐hydroxynoreremophila‐6,9‐dien‐8‐one ( 1 ), 8β‐hydroxy‐2‐dehydroxyliguhodgsonal ( 2 ), 3β‐(acetyloxy)‐11‐methoxy‐8‐oxoeremophila‐6,9‐dien‐12‐oic acid ( 3 ), 3β‐(acetyloxy)‐11‐(2′‐methylbutanoyloxy)‐8‐oxoeremophila‐6,9‐dien‐12‐oic acid ( 4 ), and 3β‐(acetyloxy)‐6α‐hydroxyligularenolide ( 5 ), along with the three known compounds 6 – 8 , were isolated from the roots of Ligularia przewalskii. The structures of the new compounds were elucidated through spectral studies including HR‐EI‐MS, IR, and NMR data.     

Synthesis of 4‐Aryl‐4,6‐dihydropyrimido[4,5‐d]pyridazine‐2,5(1H,3H)‐diones from Biginelli Compounds

Biginelli compounds 1 were first brominated at Me? C(6) with 2,4,4,6‐tetrabromocyclohex‐2,5‐dien‐1‐one to give Br₂CH? C(6) derivatives 2 . The hydrolysis of the 6‐(dibromomethyl) group of 2c to give the 6‐formyl derivative 3c in the presence of an expensive Ag salt followed by reaction with N₂H₄?H₂O yielded tetrahydropyrimido[4,5‐d]pyridazine‐2,5(1H,3H)‐dione ( 4c ; Scheme 1). However, treatment of the 6‐(dibromomethyl) derivatives 2 directly with N₂H₄?H₂O led to the fused heterocycles 4 in better overall yield (Schemes 1 and 2; Table).