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.     

Biotransformation of Vermitaline by Cunninghamella echinulata

Biotransformation of vermitaline ( 1 ) by Cunninghamella echinulata (ACCC 30369) was carried out. Four biotransformation products were obtained and three of them were characterized as new compounds. On the basis of their NMR and mass‐spectral data, their structures were characterized as 7α‐hydroxyrubijervine ( 2 ), 7α‐hydroxyrubijervine‐7‐O‐β‐D ‐galactofuranoside ( 3 ), 7α‐hydroxyvermitaline ( 4 ), and 7α‐hydroxyvermitaline‐7‐O‐β‐D ‐galactofuranoside ( 5 ).     

Flavonol Glycosides with α‐Glucosidase Inhibitory Activities and New Flavone C‐Diosides from the Leaves of Machilus konishii

Seventeen flavonoids, five of which are flavone C‐diosides, 1 – 5 , were isolated from the BuOH‐ and AcOEt‐soluble fractions of the leaf extract of Machilus konishii. Among 1 – 5 , apigenin 6‐C‐β‐D ‐xylopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 2 ), apigenin 8‐C‐α‐L ‐arabinopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 4 ), and apigenin 8‐C‐β‐D ‐xylopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 5 ) are new. Both 4 and 5 are present as rotamer pairs. The structures of the new compounds were elucidated on the basis of NMR‐spectroscopic analyses and MS data. In addition, the ¹H‐ and ¹³C‐NMR data of apigenin 6‐C‐α‐L ‐arabinopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 3 ) were assigned for the first time. The isolated compounds were assayed against α‐glucosidase (type IV from Bacillus stearothermophilus). Kaempferol 3‐O‐(2‐β‐D ‐apiofuranosyl)‐α‐L ‐rhamnopyranoside ( 12 ) was found to possess the best inhibitory activity with an IC₅₀ value of 29.3 μM .     

A new Sequiterpenoid from Eupatorium adenophorum Spreng

A new sequiterpenoid compound 8aα-hydroxy-1-isopropyl-4,7-dimethyl-1,2,3,4,6,8a-hexahydro-naphthalene-2,6-dione(1),together with seven known compounds anti-HH-dimer-coumarin(2),(-)-5-exo-hydroxy-bomeol(3),O-hydroxyl cinnamic acid(4),9β-hydroxy-ageraphorone(5),10Hα-9-oxo-ageraphorone(6),10Hβ-9-oxo-ageraphorone(7)and 9-oxo-10,11-dehydroageraphorone 8,was isolated from the leaves of Eupatorium adenopho-rum Spreng.The structures were elucidated by IR,~1H and ~(13)C NMR,EIMS,HMBC and single-crystal X-ray spec-tral data.     

New oxidized sterols from Aspergillus awamori and the endo‐boat conformation adopted by the cyclohexene oxide system

Two new oxidized sterols 1 and 2 were obtained from the active fraction of a mangrove fungus Aspergillus awamori isolated from the soils around the mangrove plant Acrostichum speciosum. Their structures were elucidated using spectroscopic methods as 22E‐7α‐methoxy‐5α,6α‐epoxyergosta‐8(14),22‐dien‐3β‐ol (1) and 22E‐3β‐hydroxy‐5α,6α,8α,14α‐diepoxyergosta‐22‐en‐7‐one (2). The NMR data and complete assignments for both DMSO‐d₆ and CDCl₃ were given. Their cytotoxic activity against A549 cell line was evaluated. Furthermore, the detailed conformation analysis for ring B (cyclohexene oxide system) of sterol 1 was given on the basis of NOEs. The endo‐boat conformation was considered as the preferred conformation for ring B rather than half‐chair conformation. Copyright © 2009 John Wiley & Sons, Ltd.     

Insights into the Synthesis of Steroidal A‐Ring Olefins

The classical synthesis, followed by purification of the steroidal A‐ring Δ¹‐olefin, 5α‐androst‐1‐en‐17‐one ( 5 ), from the Δ¹‐3‐keto enone, (5α,17β)‐3‐oxo‐5‐androst‐1‐en‐17‐yl acetate ( 1 ), through a strategy involving the reaction of Δ¹‐3‐hydroxy allylic alcohol, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate ( 2 ), with SOCl₂, was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric Δ²‐olefin 6 as a by‐product, which could only be detected on the basis of NMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5 . The same synthetic strategy was applied, using the Δ⁴‐3‐keto enone, 3‐oxoandrost‐4‐en‐17β‐yl acetate ( 8 ), as starting material, to prepare the potent aromatase inhibitor Δ⁴‐olefin, androst‐4‐en‐17‐one ( 15 ). Unexpectedly, a different aromatase inhibitor, the Δ^3,5‐diene, androst‐3,5‐dien‐17‐one ( 12 ), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8 . The data now presented show the unequal reactivity of the two steroidal A‐ring Δ¹‐ and Δ⁴‐3‐hydroxy allylic alcohol intermediates, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate ( 2 ) and 3β‐hydroxyandrost‐4‐en‐17β‐yl acetate ( 9 ), towards SOCl₂, and provides a new strategy for the preparation of the aromatase inhibitor 12 . Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by‐products.     

A New Abietane Diterpenoid from Plectranthus bishopianus Benth.

Chemical examination of the MeOH extract of Plectranthus bishopianus Benth ., a rare and endangered plant, resulted in isolation of a new abietane diterpene, 6β‐hydroxy‐7α‐methoxyroyleanone ( 1 ), along with two more diterpenoids, 6,7‐dehydroroyleanone, and 6β,7α‐dihydroxyroyleanone, a triterpene oleanolic acid, and two sterols, β‐sistosterol and stigmasterol. The structures of the isolated compounds were elucidated on the basis of spectroscopic data and also by comparison with authentic samples.     

Steroidal Alkaloids from the Roots and Rhizomes of Vertrum nigrum L.

Two new steroidal alkaloids, neoverapatuline ( 1 ) and (1β,3α,5β)‐1,3‐dihydroxyjervanin‐12‐en‐11‐one ( 2 ), together with the four known compounds, veratramine ( 3 ), rubijervine ( 4 ), veratrosine ( 5 ), and veratroylzygadenine ( 6 ), were isolated from the roots and rhizomes of Veratrum nigrum L. Their structures were established through combined analyses of physicochemical properties and spectroscopic evidence. All compounds 1 – 6 were tested for their cytotoxicities in vitro against the human glioma cell line SF188.     

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.     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

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.     

Five New Tetranortriterpenoids from the Seeds of Toona ciliata

Five new tetranortriterpenoids, toonaciliatones B–F ( 1 – 5 , resp.), together with four known compounds, dihydrocedrelone ( 6 ), cedrelone ( 7 ), 6α‐acetoxyazadirone ( 8 ), and 6α‐acetoxy‐14β,15β‐epoxyazadirone ( 9 ), were isolated from the seeds of Toona ciliata. Their structures were elucidated by spectroscopic methods, including 1D‐ and 2D‐NMR spectroscopy.     

A New Lycopodine Alkaloid from Phlegmariurus yunnanensis Ching

A new lycopodine alkaloid, 15α‐methyllycopodane‐5β,6β‐diol N‐oxide ( 1 ), was isolated from the whole plants of Phlegmariurus yunnanensis Ching , together with the two known alkaloids 15α‐methyllycopodane‐5β,6β‐diol ( 2 ) and lycoposerramine H ( 3 ), and four serratene‐type triterpenoids, serratenediol‐3‐acetate ( 4 ), serratenediol ( 5 ), lycocryptol ( 6 ), and serratriol ( 7 ). Their structures were elucidated on the basis of spectroscopic analyses, including HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR, DEPT, ¹H,¹H‐COSY, HSQC, HMBC, and NOESY.     

Xanthones with α‐Glucosidase Inhibitory Activities from Aspergillus versicolor,a Fungal Endophyte of Huperzia serrata

Three new xanthones, namely huperxanthones A–C ( 1 – 3 , resp.), were obtained from the cultures of Aspergillus versicolor, a fungal endophyte of Huperzia serrata, together with 1,7‐dihydroxy‐8‐(methoxycarbonyl)xanthone‐3‐carboxylic acid ( 4 ), β‐diversonolic acid methyl ester ( 5 ), 4‐hydroxyvertixanthone ( 6 ), and sydowinin B ( 7 ). The structures of the new compounds were established by detailed NMR and MS analysis, especially by 2D‐NMR experiments. All xanthones were evaluated for their effects on α‐glucosidase. Compound 4 exhibited a potent inhibitory activity against α‐glucosidase with an IC₅₀ value of 0.24 mM (vs. 0.38 mM for acarbose). The rest of the compounds showed weak or no activity against α‐glucosidase.     

Three New Alkaloids from the Leaves of Uncaria rhynchophylla

Three new alkaloids, 2′‐O‐β‐D ‐glucopyranosyl‐11‐hydroxyvincoside lactam ( 1 ), 22‐O‐demethyl‐22‐O‐β‐D ‐glucopyranosylisocorynoxeine ( 2 ), and (4S)‐corynoxeine N‐oxide ( 3 ) were isolated from the leaves of Uncaria rhynchophylla, together with four known tetracyclic oxindole or indole alkaloids, isocorynoxeine N‐oxide ( 4 ), rhynchophylline N‐oxide ( 5 ), isorhynchophylline N‐oxide ( 6 ), and dihydrocorynantheine ( 7 ), and an indole alkaloid glycoside, strictosidine ( 8 ). The structures of 1 – 3 were elucidated by spectroscopic methods including UV, IR, ESI‐TOF‐MS, 1D‐ and 2D‐NMR, as well as CD experiments. The activity assay showed that 8 (IC₅₀=8.3 μM ) exhibited potent inhibitory activity on lipopolysaccharide(LPS)‐induced nitrogen monoxide (NO) release in N9 microglia cells. However, only weak inhibitory activities were observed for 1 – 7 (IC₅₀>100 μM for 1 – 6 or >30 μM for 7 ).     

Two New Lycodine Alkaloids from Lycopodiastrum casuarinoides

Two new lycodine alkaloids, 11β‐methoxyhuperzine B ( 1 ) and 16‐oxohuperzinine ( 2 ), together with seven known ones, huperzinine N‐oxide, huperzine D, casuarinine A, huperzine B, casuarinine B, huperzinine, and N‐methyllycodine, were isolated from whole plants of Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic methods, including NMR and MS experiments.     

New Bisabolane Sesquiterpenes from the Rhizomes of Curcuma xanthorrhiza Roxb. and Their Inhibitory Effects on UVB‐Induced MMP‐1 Expression in Human Keratinocytes

Two new bisabolane sesquiterpenoids, 1 and 2 , along with five known ones, 13‐hydroxyxanthorrhizol ( 3 ), 12,13‐epoxyxanthorrhizol ( 4 ), xanthorrhizol ( 5 ), β‐curcumene ( 6 ), and β‐bisabolol ( 7 ), were isolated from the rhizomes of Curcuma xanthorrhiza Roxb . The chemical structures of the new compounds were determined to be (7R,10R)‐10,11‐dihydro‐10,11‐dihydroxyxanthorrhizol 3‐O‐β‐D ‐glucopyranoside ( 1 ) and (?)‐curcuhydroquinone 2,5‐di‐O‐β‐D ‐glucopyranoside ( 2 ) on the basis of 1D‐ and 2D‐NMR spectroscopic analyses and optical‐rotation characteristics. Compounds 2 and 3 decreased MMP‐1 expression in UVB‐treated human keratinocytes by ca. 8.9‐ and 7.6‐fold at the mRNA level, and by ca. 9.2‐ and 6.6‐fold at the protein level, respectively. The results indicate that the isolated compounds may have anti‐aging effects through inhibition of MMP‐1 expression in skin cells.     

Synthesis of Novel Bis(β‐cyclodextrin)s Linked with Glycol and Their Inclusion Complexation with Organic Dyes

Three novel bis(β‐cyclodextrin (CD))s with flexible glycol linkers, i.e., ethylene glycol‐bridged bis(6‐hydroxy‐6‐deoxy‐β‐CD) ( 2 ), diethylene glycol‐bridged bis(6‐hydroxy‐6‐deoxy‐β‐CD) ( 3 ), and triethylene glycol‐bridged bis(6‐hydroxy‐6‐deoxy‐β‐CD) ( 4 ) have been synthesized by the reaction of mono[6‐O‐(p‐toluenesulfonyl)]‐β‐CD with corresponding materials. The inclusion complexation behaviors of these compounds 2 – 4 with organic dyes; that is, acridine red (=N‐[(3Z)‐6‐(methylamino)‐3H‐xanthen‐3‐ylidene]methanaminium chloride; AR), neutral red (=N⁸,N⁸,3‐trimethylphenazine‐2,8‐diamine hydrochloride; NR), ammonium 8‐anilinonaphthalene‐1‐sulfonate (ANS), sodium 6‐(p‐toluidinyl)‐naphthalene‐2‐sulfonate (TNS), rhodamine B (RhB) and brilliant green (=N‐(4‐{[4‐(diethylamino)cyclohexa‐2,5‐dien‐1‐yl](phenyl)methyl}cyclohex‐2‐en‐1‐ylidene)‐N‐ethyl‐ethanaminium hydrogen sulfate; BG), have been investigated at 25° in phosphate buffer (pH 7.20) by ultraviolet, fluorescence, and 2D‐NMR spectroscopy. The results indicate that the two linked CD units may cooperatively bind a guest, and the molecular binding ability toward dye guests, especially bent ANS, T‐shaped RhB, and triangular BG, can be extended. This cooperative binding mode is confirmed by Job's experiments and 2D‐NMR investigations. Furthermore, the complex stability depends greatly on the linker length of these glycol‐bridged bis(β‐CD)s and the size and shape of guest. The higher binding ability and selectivity of dye molecules by bis(β‐CD)s 2 – 4 are discussed from the viewpoint of size/shape‐fit concept and multiple recognition mechanism.     

Two New Lycopodium Alkaloids from Lycopodium obscurum

Two new Lycopodium alkaloids, (+)‐cermizine D N‐oxide ( 1 ) and (8β)‐8‐(acetyloxy)obscurumine A ( 2 ), along with five known compounds, were isolated from the crude alkaloid portion of Lycopodium obscurum. Their structures were elucidated on the basis of spectroscopic data and chemical correlation. All of these alkaloids were tested in an assay for acetylcholine esterase (AChE) inhibitory activity.     

Base‐Induced Decarboxylation of Polyunsaturated α‐Cyano Acids Derived from Malonic Acid: Synthesis of Sesquiterpene Nitriles and Aldehydes with β‐, φ‐, and ψ‐End Groups

Catalytic base‐induced decarboxylation of polyunsaturated α‐cyano‐β‐methyl acids derived from malonic acid led to the corresponding nitriles 3 (Schemes 2 and 3), 6 (Scheme 5), and 9 (Scheme 6). This decarboxylation occurred with previous deconjugation of the α,β‐alkene moiety of the α‐cyano‐β‐methyl acid, leading to an α‐cyano‐β‐methylene propanoic acid which was easily decarboxylated (see Scheme 2). β‐Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6 , and 9 were reduced to the sesquiterpene aldehydes 4 (β‐end group), 7 (φ‐end group), and 10 (ψ‐end group), respectively.