Chemical Constituents from Annona Glabra

A new kaurane diterpenoid, annoglabasin G (16α‐hydro‐19‐acetoxy‐ent‐kauran‐17‐al) ( 1 ), along with 27 compounds including 18 kaurane diterpenoids, 16β‐hydro‐ent‐kauran‐17‐oic acid ( 2 ), 16α‐hydro‐ent‐kauran‐17‐oic acid ( 3 ), 19‐nor‐ent‐kauran‐4α‐ol‐17‐oic acid ( 4 ), 16α‐hydro‐19‐ol‐ent‐kauran‐17‐oic acid ( 5 ), ent‐kaur‐16‐en‐19‐oic acid ( 6 ), 16α‐hydroxy‐ent‐kauran‐19‐oic acid ( 7 ), 16α,17‐dihydroxy‐ent‐kauran‐19‐oic acid ( 8 ), 16β,17‐dihydroxy‐ent‐kauran‐19‐oic acid ( 9 ), 16α‐hydro‐ent‐kauran‐17,19‐dioic acid ( 10 ), 16β‐hydroxy‐17‐acetoxy‐ent‐kauran‐19‐oic acid ( 11 ), 16β‐hydro‐17‐hydroxy‐ent‐kauran‐19‐al ( 12 ), 16α‐hydro‐17‐hydroxy‐ent‐kauran‐19‐al ( 13 ), 16β,17‐dihydroxy‐ent‐kauran‐19‐al ( 14 ), 16α‐hydro‐19‐al‐ent‐kauran‐17‐oic acid ( 15 ), 16α‐hydro‐17‐acetoxy‐ent‐kauran‐19‐al ( 16 ), 16α‐hydro‐19‐acetoxy‐ent‐kauran‐17‐oic acid ( 17 ), ent‐kaur‐15‐en‐19‐oic acid ( 18 ) and ent‐kaur‐15‐en‐17‐ol‐19‐oic acid ( 19 ); four acetogenins, annomontacin ( 20 ), annonacin ( 21 ), isoannonacinone ( 22 ) and squamocin ( 23 ); four steroids, β‐sitosterol ( 24 ), stigmasterol ( 25 ), β‐sitosteryl‐D‐glucoside ( 26 ) and stigmasteryl‐D‐glucoside ( 27 ) and one oxoaporphine, liriodenine ( 28 ), were isolated from the fresh fruits of Annona glabra. These compounds were characterized and identified by physical and spectral evidence.     

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.     

A Diterpenoid with a New Skeleton and Cytotoxic Terpenoids Isolated from Amentotaxus formosana

The new diterpenoid 6α‐hydroxy‐ent‐kaur‐16‐en‐15‐one ( 1 ) and a diterpenoid with a new skeleton, i.e., amentotaxin BB ( 5 ), as well as three new lanostanoids, i.e., (3β,23R)‐3‐methoxy‐24‐methylenelanost‐8‐en‐23‐ol ( 6 ), (23S)‐23‐methoxy‐24‐methylenelanost‐8‐en‐3‐one ( 7 ), and (3β,24ξ)‐3‐methoxy‐24‐methyl‐9,19‐cyclolanostan‐25‐ol ( 8 ), were isolated from the bark and leaves of Amentotaxus formosana. Their structures, including the relative configurations, were elucidated from spectroscopic data. Compound 1 and a known compound, ent‐kaur‐16‐en‐15‐one ( 2 ), showed potent cytotoxic effects against a number of cancer cells in vitro.     

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.     

Three New Cytotoxic ent‐Kaurane Diterpenoids from Isodon weisiensis C. Y. Wu

Three new cytotoxic ent‐kaurane diterpenoids, (1α,7α,14β)‐1,7,14‐trihydroxy‐ent‐kaur‐16‐en‐15,18‐dione ( 1 ), (1α,7α,14β)‐1,7,14,18,20‐pentahydroxy‐ent‐kaur‐16‐en‐15‐one ( 2 ), and (3β,7α,14β)‐3,7,14‐tris(acetyloxy)‐ent‐kaur‐16‐en‐15‐one ( 3 ), were isolated from Isodon weisiensis C. Y. Wu. Their structures were elucidated by spectroscopic methods, including 2D‐NMR techniques, and the crystal structure of 1 was determined by single‐crystal X‐ray‐diffraction analysis. The chosen crystal of 1 was orthorhombic, space group P2₁2₁2₁, and there were two molecules with little difference in bond length and bond angle in the least‐asymmetry unit. Compounds 1–3 showed significant cytotoxic activities against human‐cancer cell lines Bel‐7402 and HO‐8910.     

Two New C(20)‐Oxygenated ent‐Kaurene Diterpenoids from Isodon henryi

Two new C(20)‐oxygenated ent‐kaurene diterpenoids, taibaihenryiins A ( 1 ) and B ( 2 ), along with five known compounds, shikokianin ( 3 ), longikaurin D, 2α‐hydroxyursolic acid, longikaurin F, and lasiodin, were isolated from the EtOH extract of the leaves and tender branches of Isodon henryi (Hemsl .) Kudo . The structures of the new compounds were determined as 11α‐acetoxy‐7,20‐epoxy‐1α,6β,7β‐trihydroxy‐ent‐kaur‐16‐en‐15‐one ( 1 ) and 7,20‐epoxy‐3β,6β,7β,11α‐tetrahydroxy‐ent‐kaur‐16‐en‐15‐one ( 2 ) on the basis of detailed spectroscopic analyses.     

Two New Diterpenoids from Callicarpa pedunculata

Two new diterpenoids, pedunculatic acid A (= (4R,5α,7α)‐7‐ethoxy‐9β,13β‐dioxyabiet‐8(14)‐en‐18‐oic acid; 1 ) and pedunculatic acid B (= (4S,5α,12β)‐8β,14β‐epoxy‐12‐hydroxy‐11‐oxototaran‐19‐oic acid; 2 ), together with three known sesquiterpenoids, were isolated from the Chinese medicinal herb Callicarpa pedunculata R. Brown . Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR, and by high‐resolution mass spectrometry.     

The Chemical Constituents from the Callus Culture of Trewia nudiflora

Five ent‐atisane diterpenoids, including three new ones, i.e., (16α)‐17‐hydroxy‐ent‐atisan‐19‐oic acid methyl ester ( 1 ), (16α)‐17‐dihydroxy‐ent‐atisan‐19‐oic acid methyl ester ( 2 ), (16α)‐ent‐atisan‐16,17,19‐triol ( 3 ), and two known compounds, i.e., 17‐hydroxy‐ent‐atisan‐19‐oic acid ( 4 ), (16α)‐16,17‐dihydroxy‐ent‐atisan‐19‐al ( 5 ), together with one known diterpene glycoside, i.e., sumogaside, two known triterpenes, i.e., germanicone and (3β)‐β‐amyrin, three known phenolic compounds, i.e., (+)‐gallocatechin, (+)‐catechin, and gallic acid, and two known sterols, i.e., β‐sitosterol and daucosterol, were isolated from the callus cultures of Trewia nudiflora. Their structures were elucidated by spectroscopic analysis including 1D‐ and 2D‐NMR experiments. No maytansinoids were isolated or detected by LC‐ESI‐MS in the extracts of the calli, which suggests that the callus cultures can not produce maytansinoids under these conditions.     

Two New Diterpenoids and other Constituents from Isodon Nervosus

Two new ent‐kaurane diterpenoids, 15β‐hydroxy‐6,7‐seco‐6,11β:6,20‐diepoxy‐1α,7‐olide‐ent‐kaur‐16‐ene ( 1 ), 11α,15α‐dihydroxy‐6β‐methoxy‐6,7‐seco‐6,20‐epoxy‐1α,7‐olide‐ent‐kaur‐16‐ene ( 2 ), together with four known diterpenoids, nodosin ( 3 ), isodocarpin ( 4 ), odonicin ( 5 ) and maoyecrystal F ( 6 ) were isolated from the aerial parts of Isodon nervosus. The structures of the new compounds were elucidated on the basis of their spectral evidence, especially on 2D NMR.     

Two New Triterpene and a New Nortriterpene Glycosides from Phlomis viscosa

The isolation and structure elucidation of two new oleanane‐type triterpene glycosides, 29‐(β‐D ‐glucopyranosyloxy)‐2α,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid (=(2α,3β,4α,29α)‐29‐(β‐D ‐glucopyranosyloxy)‐2,3,23‐trihydroxyolean‐12‐en‐28‐oic acid; 1 ) and its C(20)‐epimer, 30‐(β‐D ‐glucopyranosyloxy)‐2α,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid (=(2α,3β,4α,29β)‐29‐β‐D ‐glucopyranosyloxy)‐2,3,23‐trihydroxyolean‐12‐en‐28‐oic acid; 2 ), and a novel nortriterpene glycoside, (17S)‐2α,18β,23‐trihydroxy‐3,19‐dioxo‐19(18→17)‐ abeo‐28‐norolean‐12‐en‐25‐oic acid β‐D ‐glucopyranosyl ester (=(1R,2S,4aS,4bR,6aR,7R,9R,10aS,10bS)‐3,4,4a,4b,5,6,6a,7,8,9,10,10a,10b,11‐tetradecahydro‐1‐hydroxy‐7‐(hydroxymethyl)‐3′,4′,4a,4b,7‐pentamethyl‐2′,8‐ dioxospiro[chrysene‐2(1H),1′‐cyclopentane]‐10a‐carboxylic acid β‐D ‐glucopyranosyl ester; 3 ) from Phlomis viscosa (Lamiaceae) are reported. The structures of the compounds were asigned by means of spectroscopic (IR, 1D‐ and 2D‐NMR, and LC‐ESI‐MS) and chemical (acetylation) methods.     

Novel ent‐Abietane Diterpenoids from Isodon eriocalyx var. laxiflora

Two novel ent‐abietane diterpenoids, 3α,20‐epoxy‐6β‐hydroxy‐1,7‐dioxo‐ent‐abiet‐15(17)‐en‐16‐oic acid ( 1 ) and ent‐abieta‐7,15(17)‐diene‐3β,16,18‐triol ( 2 ) were isolated from Isodon eriocalyx var. laxiflora. Their structures were determined by extensive spectroscopic analysis and confirmed by X‐ray crystallography. Compound 1 is an unprecedented example that establishes that a naturally occurring ent‐abietane diterpenoid can have an oxygenation pattern almost identical to those of 3α,20‐epoxy‐ent‐kaurane diterpenoids.     

Diterpenoids from Isodon Eriocalyx

Two new diterpenoids, Maoecrystal U and epi‐maoecrystal P , together with nine known diterpenoids and eight other known compounds were isolated from Isodon eriocalyx ( ). The structures of two new diterpenoids were elucidated as 6β‐acetoxy‐15β‐hydroxy‐3α,20‐epoxy‐ent‐kaur‐16‐ene‐1,7‐dione and 16(S)‐methoxymethy‐6β,7β‐dihydroxy‐7α,20‐epoxy‐ent‐kaur‐2,3‐ethenylene‐1,15‐dione on the basis of spectroscopic evidence, especially by 2D NMR techniques.     

Cyclopeptide and Terpenoids from Tripterygium wilfordii Hook. f.

The EtOH extract of dried root bark of Tripterygium wilfordii Hook. f. (Celastraceae) afforded a novel macrolactone cyclopeptide named triptotin L (=cyclo[L ‐alanyl‐L ‐alanyl‐3‐(4,4,9‐trimethyldecyl‐3‐hydroxypropanoylglycyl‐L ‐valyl‐L ‐leucyl; 1 ), the new triterpene 2β,6α,22β‐trihydroxy‐24,29‐dinor‐D:A‐friedoolean‐4‐ene‐3,21‐dione named 6α‐hydroxytriptocalline A (=(2β,6α,8α,9β,10α,13α,14β,20β,22β)‐2,6,22‐trihydroxy‐9,13‐dimethyl‐24,25,26,30‐tetranorolean‐4‐ene‐3,21‐dione; 2 ), the new diterpenoid 11,16‐dihydroxy‐14‐methoxy‐18(4→3) abeo‐abieta‐3,8,11,13‐tetraene‐18‐oic acid named 16‐hydroxytriptobenzene H (=(4aS,10aS)‐3,4,4a,9,10,10a‐hexahydro‐5‐hydroxy‐7‐(2‐hydroxy‐1‐methylethyl)‐8‐methoxy‐1,4a‐dimethylphenanthrene‐2‐carboxylic acid; 3 ), and the abietane diterpenoid alkaloid named triptotin J (=(7aS,11aS,11bS)‐7,7a,8,9,10,11,11a,11b‐octahydro‐11b‐hydroxy‐α,α,8,8,11a‐pentamethyl‐6H‐naphth[1,2‐d]azepine‐4‐methanol; 4 ). Their structures were established on the basis of spectroscopic studies.     

Diterpenes and Disulfides from the Marine Mangrove Plant Bruguiera sexangula var. rhynchopetala

Phytochemical investigation of the stems of Bruguiera sexangula var. rhynchopetala resulted in the isolation and characterization of four new and seven known secondary metabolites. The new compounds were spectroscopically identified as 17‐hydroxy‐16‐oxobeyer‐9(11)‐en‐19‐al ( 1 ), 16,17‐dihydroxy‐19‐nor‐ent‐kaur‐9(11)‐en‐3‐one ( 2 ), (16R)‐13,17‐epoxy‐16‐hydroxy‐ent‐kaur‐9(11)‐en‐19‐al ( 3 ), and (−)‐3,4‐dihydro‐3‐hydroxy‐7‐methoxy‐2H‐1,5‐benzodithiepine‐6,9‐dione ( 10 ). The configurations of the known compounds brugierol ( 11 ) and isobrugierol ( 12 ) were re‐investigated. Compounds 11 and 12 , together with 2,6‐dimethoxy‐1,4‐benzoquinone ( 13 ), are proposed to be degradation products of the novel, unusual disulfide 10 (Scheme).     

Synthesis of Natural Atisane‐Type Diterpenoids by retro‐Biomimetic Transformations

An efficient one step, retro‐biomimetic procedure for the synthesis of natural products having the atisane structure is described (Scheme 2), natural products which are components of medicinal plants and possess relevant biological activity. Their structures were confirmed by chemical transformations and spectral data. The starting materials were the known ent‐kaur‐16‐en‐19‐oic acid ( 1 ) and ent‐trachyloban‐19‐oic acid ( 2 ), diterpenoids readily available from the waste of sunflower.     

Rubescensins S and T: Seco‐ent‐Kaurane Diterpenoids from Isodon rubescens var. taihangensis

Two new diterpenoids, rubescensin S (=(1α,6β,14β)‐7α,20‐epoxy‐1,7,14‐trihydroxy‐16‐oxo‐15,16‐seco‐ent‐kauran‐6,15‐olide; 1 ) and rubescensin T (=(1α,6β,11β,20S)‐7α,20‐epoxy‐1,6,7‐trihydroxy‐20‐methoxy‐8,15‐seco‐ent‐kaur‐16‐en‐11,15‐olide; 2 ) were isolated from the Chinese medicinal herb Isodon rubescens var. taihangensis. Compound 1 possesses a unique, unprecedented 15,16‐seco‐ent‐kaurane skeleton. Both compounds exhibited cytotoxic activities against K562 human leukemia cells.     

New Cytotoxic Triterpenoids from the Aerial Parts of Euphorbia sieboldiana

Phytochemical investigation of the EtOH extract of Euphorbia sieboldiana led to the isolation of four new oleanane‐type triterpenoids, (1β,2α,3β,19β)‐1,2,3,19‐tetrahydroxyolean‐12‐en‐28‐oic acid, (1β,3β,19β)‐1,3,19‐trihydroxyolean‐12‐en‐28‐oic acid, (1β,2α,3β,16β,19β)‐1,2,3,16,19‐pentahydroxyolean‐12‐en‐28‐oic acid, and (1β,2α,3β,19β,23)‐1,2,3,19,23‐pentahydroxyolean‐12‐en‐28‐oic acid, along with 16 known compounds. Their structures were established by extensive 1D‐ and 2D‐NMR, as well as other spectral analyses. Biological evaluation of the four new triterpenoids revealed potent cytotoxic activities against HeLa and Hep‐G2 cells.     

Triterpenoids from the Mangrove Plant Hibiscus tiliaceus

Three new triterpenoids with the rarely occurring nigrum skeleton, namely (20E)‐22‐hydroxynigrum‐20‐en‐3‐one ( 1 ), 21β‐hydroxynigrum‐22(29)‐en‐3‐one ( 2 ), and 21α‐hydroxynigrum‐22(29)‐en‐3‐one ( 3 ), were isolated from the mangrove plant Hibiscus tiliaceus. Additionally, five known triterpenoids including friedelin ( 4 ), 12‐oleanen‐3β‐ol ( 5 ), 3β‐hydroxy‐12‐oleanen‐28‐oic acid ( 6 ), 20(29)‐lupen‐3β,28‐diol ( 7 ), and cucurbita‐5,23‐dien‐3β,25‐diol ( 8 ) were also isolated and identified. The latter structures were elucidated by a detailed NMR and MS analyses, as well as by comparison with reported literature data.     

Three New ent‐Trachylobane Diterpenoids from Co‐cultures of the Calli of Trewia nudiflora and Fusarium sp. WXE

Five diterpenoids, including three new ent‐trachylobane diterpenoids, i.e., (3α)‐3‐hydroxy‐ent‐trachylobane‐17,19‐dioic acid 19‐methyl ester ( 1 ), ent‐trachylobane‐17,19‐dioic acid 19‐methyl ester ( 2 ), ent‐trachylobane‐17,19‐dioic acid ( 3 ), and two known atisane‐type ones, i.e., (16α)‐16,17‐dihydroxy‐ent‐atisan‐19‐oic acid methyl ester ( 4 ), and 17‐hydroxy‐ent‐atisan‐19‐oic acid methyl ester ( 5 ), were isolated from the co‐culture extract of the calli of Trewia nudiflora and its endophytic fungus Fusarium sp. WXE. Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR experiments, and HR‐Q‐TOF mass spectrometry. The antitumor and antibacterial properties of the new compounds were evaluated.     

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.