Two New Diterpenoids and Other Constituents from Isodon japonicus

Two new ent‐kaurene diterpenoids, 15α,20‐dihydroxy‐6,7‐seco‐entkaur‐16‐ene‐7,1α(6,11α)‐diolide ( 1 ), 6β‐butyroxy‐3β‐hydroxy‐6,7‐seco‐6,20‐epoxy‐7,1α‐olide‐entkaur‐16‐en‐15‐one ( 2 ), together with 25 known compounds, 3 – 27 , were isolated from the leaves of Isodon japonicus. Their structures were established by spectroscopic methods, including 2D‐NMR techniques.     

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.     

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.     

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.     

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.     

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.     

ent‐Kaurane Diterpenoids from Isodon japonicus

Two new 6,7‐seco‐ent‐kaurane diterpenoids, isojaponins A ( 1 ) and B ( 2 ), together with 18 known ent‐kaurane diterpenoids were isolated from the aerial parts of Isodon japonicus. The structures of the two new compounds were elucidated by extensive 1D‐ and 2D‐NMR spectroscopic methods in combination with MS experiments.     

Cytotoxic Diterpenoids from the Stem Bark of Annona squamosa L.

Three new ent‐kaurane diterpenoids, (4α)‐19‐nor‐ent‐kaurane‐4,16,17‐triol ( 1 ), (4α,16α)‐17‐(acetyloxy)‐19‐nor‐ent‐kaurane‐4,16‐diol ( 2 ), and 17‐hydroxy‐ent‐kaur‐15‐en‐19‐al ( 3 ), together with 11 known compounds, were isolated from the stem bark of Annona squamosa L. The structures of 1 – 3 were identified by analysis of their spectroscopic data. All compounds were evaluated for cytotoxic activity against human lung cancer (95‐D) and ovarian cancer (A2780) cell lines, and compounds 3, 5, 7, 11 – 14 exhibited promising antiproliferative activities with IC₅₀ values ranging from 0.38 to 34.66 μM .     

Two new diterpenoids from Isodon serra

From the aerial part of Isodon serra,two new ent-6,7-seco-kaurane-type diterpenoids,15α,20β-dihydroxy-6β-methoxy-6,7- seco-6,20-epoxy-1,7-olide-ent-kaur-16-ene (1) and 6α,15α-dilaydroxy-20-aldehyde-6,7-seco-6,11α-epoxy-1,7-olide-ent-kaur-16- ene (2) were isolated.Their structures were elucidated by spectroscopic means.     

Two New, 1‐Oxygenated ent‐Kaurane‐Type Diterpenes from Croton kongensis

One new ent‐8,9‐secokaurane diterpene, kongensin D ( 1 ), and one new ent‐kaurane diterpene, kongensin E ( 2 ), along with one known compound, (7α)‐7,18‐dihydroxy‐ent‐kaur‐16‐en‐15‐one 18‐acetate ( 3 ), were isolated from the aerial parts of Croton kongensis. The structures of the new compounds were elucidated by means of HR‐MS and in‐depth NMR experiments, and by comparison with literature data. Compounds 1 and 2 showed an unusual oxygenation pattern with an OH or AcO group at C(1).     

Diterpenes from Xylopia langsdorffiana

The phytochemical investigation of Xylopia langsdorffiana A.St.‐Hil. & Tul . led to the isolation of eight diterpenes, i.e., of the four new compounds (5β,7β,8α,9β,10α,12α)‐atisane‐7,16‐diol 7‐acetate ( 1 ), named xylodiol 7‐acetate, (5β,8α,9β,10α,12α)‐16‐hydroxyatisan‐7‐one ( 2 ), named xylopinone, (3α,12Z)‐3‐hydroxy‐ent‐labda‐8(20),12,14‐trien‐18‐oic acid ( 3 ), named labdorffianic acid A, and 8,20‐epoxy‐13‐hydroxy‐ent‐labd‐14‐en‐18‐oic acid ( 4 ), named labdorffianic acid B, and of the four known compounds 5 – 8 , i.e., ent‐kauran‐16‐ol, ent‐kaur‐16‐en‐19‐oic acid, ent‐kaur‐16‐en‐19‐ol, and ent‐trachyloban‐18‐oic acid. The structures were established by IR, HR‐ESI‐MS, and NMR data analysis with the aid of 2D techniques.     

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 the Chinese Liverwort Chiloscyphus polyanthus

A new diterpene, (7α,11β,14β,16R)‐7,11,14‐trihydroxy‐ent‐kaur‐15‐one ( 1 ), and a new sesquiterpene, polyanthuslide ( 2 ), were isolated from the Chinese liverwort Chiloscyphus polyanthus. Their structures were determined on the basis of extensive spectroscopic analyses, and the configuration of 2 was established by X‐ray crystallographic analysis.     

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.     

Three New, 1‐Oxygenated ent‐8,9‐Secokaurane Diterpenes from Croton kongensis

Three new ent‐8,9‐secokaurane diterpenes, kongensins A–C ( 1 – 3 ), were isolated from the aerial parts of Croton kongensis, together with two known compounds, rabdoumbrosanin ( 4 ) and (7α,14β)‐7,14‐dihydroxy‐ent‐kaur‐16‐en‐15‐one ( 5 ). The structures of the new compounds were elucidated by HR‐MS as well as in‐depth 1D‐ and 2D‐NMR analyses. Compounds 1 – 3 showed an unusual oxygenation pattern, with an AcO or OH group at C(1), in combination with a Δ⁸⁽¹⁴⁾ unsaturation ( 1 ) or an 8,14‐epoxide function ( 2, 3 ).     

Kaurane-Type Diterpenoids from Liverworts

Seven kaurane-type diterpenoids were isolated from the Taiwanese liverworts Jungermannia truncata. Among them, three are new structures. They are: ent-16-kauren-3, 15-dione (6), ent-16(S)-kauran-3,15-dione (7), and ent-14α-hydroxy-16-kauren-15-one (11). From Plagiochila pulcherrima, three known kaurane alcohols were also isolated along with sesquiterpenoids plagiochilines A, B, C and ent-4β, 10α-dihydroxyaromadendrane.     

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.     

New Sesquiterpenes from Ligulariopsis Shichuana

A thorough investigation of Ligulariopsis shichuana afforded five new sesquiterpenes, including 1β,10β‐epoxy‐3α‐angeloyloxy‐9β‐acetoxy‐8α,11β‐dihydroxybakkenolide ( 1 ), 1β,7‐dihydroxy‐3β‐acetoxy‐noreremophil‐6(7),9(10)‐dien‐8‐one ( 2 ), 8α‐hydroxy‐3‐oxoeremophil‐1(2),7(11),9(10)‐trien‐8β(12)‐olide ( 3 ), 1β,10β‐dihydroxy‐3β‐acetoxyeremophil‐7(11),8(9)‐dien‐8(12)‐olide ( 4 ) and 1β,10β‐epoxy‐8,12‐dihydroxy‐3β‐acetoxy‐9β‐angeloyloxyeremophil‐7(11)‐en‐8,12‐disemiketal ( 5 ). Their structures were established by spectroscopic methods and 2D NMR techniques. In addition, bakkenolide ( 1 ) and eremophilenolides ( 5 ) showed antibacterial and cytotoxic activities.     

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.     

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.