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.     

Three New Lignan Derivatives from Lindera glauca (Siebold et Zucc.) Blume

Two new aryl‐tetralin lignan glycosides, linderanosides A and B ( 1 and 2 , resp.), and a new dihydrobenzofuran neolignan glycoside, linderanoside C ( 3 ), together with five known lignan derivatives ( 4 – 8 ) were isolated from the trunk of Lindera glauca. The structures of these new compounds were determined through spectroscopic analyses, including extensive 2D‐NMR data and acid hydrolysis. The absolute configurations of the compounds were clarified by circular dichroism (CD) spectroscopic studies. Compounds 1 – 8 were evaluated for their cytotoxicity against A549 (non‐small cell lung adenocarcinoma), SK‐OV‐3 (ovarian cancer cells), A498 (human kidney epithelial cells), and HCT‐15 (colon cancer cells) human tumor cell lines using sulforhodamine B assays in vitro.     

New Cytotoxic Meroterpenoids from the Plant Endophytic Fungus Pestalotiopsis fici

Pestalofones I – K ( 1 – 3 ), three new dimeric meroterpenoids with 2‐(7‐benzoyl‐2,3‐dihydrobenzofuran‐2‐yl)‐1‐phenylethan‐1‐one (in 1 ) and 2‐(7‐benzoyl‐2,3‐dihydrobenzofuran‐2‐yl)‐1‐(3,8‐dioxatricyclo[5.1.0.0^2,4]oct‐4‐yl)ethan‐1‐one (in 2 and 3 ) skeletons, were isolated from the solid cultures of the plant endophytic fungus Pestalotiopsis fici. The structures of 1 – 3 were elucidated by NMR experiments. Compound 1 was found to be present as a racemic mixture. The absolute configurations of 2 and 3 were deduced by analogy to the previously isolated metabolites pestalofones G and H ( 4 and 5 ) from the same fungus. Biogenetically, compounds 1 – 3 are derived from the same precursors (co‐isolated compounds 9 and 10 ) as the previously isolated compounds 4 – 8 . Compounds 2 and 3 showed weak cytotoxic activities against four human tumor cell lines T24, HeLa, A549, and MCF‐7.     

Cytotoxic Amides and Quinolones from Clausena lansium

Two new amides, claulansamides A and B ( 1 and 2 , resp.), together with five known amides, 3 – 7 and six known quinolones, 8 – 13 , were isolated from the stems and roots of Clausena lansium. Their structures were elucidated on the basis of extensive spectroscopic methods. Their absolute configurations were determined by single‐crystal X‐ray diffraction technique, CD, and optical rotation. HPLC Chiral separation of 1 afforded two enantiomers, (+)‐ and (?)‐claulansamide A, respectively. Compounds 9, 12 , and 13 were isolated from the genus Clausena for the first time. All compounds were evaluated for their cytotoxic activities against A549, BGC‐823, and HeLa cancer cell lines. However, only 9 showed cytotoxic activity against A549 cell line with an IC₅₀ value of 46.3 μM , and 11 against BGC‐823 and HeLa cell lines with the IC₅₀ values of 55.0 and 14.7 μM , respectively.     

New Dihydroagarofuranoid Sesquiterpenes from Celastrus paniculatus

The six new dihydro‐β‐agarofuranoid sesquiterpenes 1 – 6 and three known compounds were isolated from the whole plant of Celastrus paniculatus. The structures including relative configurations were elucidated by means of spectroscopic analyses. Compounds 1 – 6 were evaluated for cytotoxicity against a panel of three human‐tumor cell lines.     

Polyhydroxylated Sterols from the South China Sea Gorgonian Verrucella umbraculum

Two new polyhydroxylated sterols, named verumbsteroids A and B ( 1 and 2 , resp.), along with seven known analog, 3 – 9 , were isolated from the gorgonian Verrucella umbraculum collected from the South China Sea. The structures and relative configurations of the new compounds were elucidated by comprehensive spectroscopic investigations. The absolute configuration of 1 was determined by using modified Mosher method with the acetonide derivative of 1 . Compounds 1 and 3 – 5 were found to show cytotoxicities against five human tumor cell lines (HL‐60, K562, HeLa, A‐549, and HCT‐116) with the IC₅₀ values ranging from 2.76 to 9.62 μM .     

Phenylglycol Metabolites from Cultures of the Basidiomycete Mycena pruinosoviscida BCC 22723

Mycenadiols A–D ( 1 – 4 , resp.), phenylglycols possessing an ethynyl or vinyl (ethenyl) group were isolated from cultures of the basidiomycete Mycena pruinosoviscida BCC 22723. The structures were elucidated on the basis of NMR‐spectroscopic and mass spectrometric data. The absolute configurations of 1 and 2 were determined by synthesis. Compounds 1 – 4 are synthetically known, but, they have not been previously isolated from natural sources.     

Chemical Constituents from Termite‐associated Xylaria acuminatilongissima YMJ623

Three previously unreported benzofurans, namely acumifurans A–C ( 1 – 3 ), along with five known compounds, 2‐(isopropyl‐1′‐ol)‐2,3‐dihydrobenzofuran‐5‐carbinol ( 4 ), fomannoxin alcohol ( 5 ), fomannoxin ( 6 ), acremine S ( 7 ) and cyclo(L ‐Pro‐L ‐Leu) ( 8 ), were isolated from the ethyl acetate extracts of the fermented broths of termite n est associated Xylaria acuminatilongissima YMJ623. Compound 4 , a synthe tic benzofuran analogue of 1 – 3 , was isolated for the first time from natural resources. The str uctures of 1 – 8 were determined through spectroscopic data analyses. The absolute configurations of 1 – 4 were established based mainly on ROESY experiment and Mosher’s reaction, and compared the optical rotation data with the literatures. The effects of these compounds on the inhibition of NO production in lipopolysaccharide (LPS)‐activated murine macrophage RAW264.7 cells were also evaluated. Of the compounds tested, 6 showed a mild NO production inhibitory activity without any cytotoxicity, and its mean maximum inhibition (E_max) at 100 μM was 42.98±0.87 %.     

Two Novel 14‐Nor‐13,14‐secopodocarpanes from the Bark of Taiwania cryptomeriodes

The two novel compounds cryptomelactones A ( 3 ) and B ( 4 ) were isolated from the bark of Taiwania cryptomeriodes, besides the two known podocarpane derivatives 1β,13,14‐trihydroxypodocarpa‐8,11,13‐trien‐7‐one ( 1 ) and 3β,13,14‐trihydroxypodocarpa‐8,11,13‐trien‐7‐one ( 2 ), and were characterized by spectroscopic means including 2D‐NMR techniques. Compounds 3 and 4 are novel‐14‐nor‐13,14‐seco‐podocarpanes. The absolute configurations of 3 and 4 were determined by the modified Mosher method. The biotransformation mechanism of 3 and 4 is proposed.     

Cuparene‐Derived Sesquiterpenes from the Chinese Red Alga Laurencia okamurai Yamada

Four new cuparene‐derived sesquiterpenes, laureperoxide ( 1 ), 10‐bromoisoaplysin ( 2 ), isodebromolaurinterol ( 3 ), and 10‐hydroxyisolaurene ( 4 ), together with seven known, related sesquiterpenes, 5 – 11 , have been isolated from the red alga Laurencia okamurai. Their structures were determined on the basis of detailed spectroscopic analyses and comparison with known compounds. Compounds 8 – 11 were shown for the first time to represent true natural products, and the full ¹H‐ and ¹³C‐NMR assignments of 5 are reported for the first time.     

Monoterpenoid Indole Alkaloids Bearing an N4‐Iridoid from Gelsemium elegans

Five new alkaloids, gelseganines A–D ( 1 – 4 ) and humantenine N₄‐oxide ( 5 ), were isolated from the stems and leaves of Gelsemium elegans. Compounds 1 – 4 represent a rare class of monoterpenoid indole alkaloids that bear an N₄‐iridoid unit. The structures of 1 – 5 were determined by spectroscopic analysis, single‐crystal X‐ray diffraction, and chemical correlation, and their absolute configurations were elucidated by CD analysis. A plausible biogenetic pathway for alkaloids 1 – 5 was also postulated.     

Polyoxygenated Cyclohexene Derivatives from Uvaria rufa

Four new polyoxygenated cyclohexene derivatives, uvarirufone A ( 1 ) and uvarirufols A–C ( 2 – 4 ), along with ten related known compounds, were isolated from the EtOH extract of the aerial parts of Uvaria rufa Bl . Their structures and absolute configurations were determined by in‐depth spectroscopic and spectrometric methods in combination with molecular modeling.     

交让木树皮中的新虎皮楠生物碱的结构研究

本文报道从虎皮楠科植物交让木的树皮中分到4个新的和7个已知的虎皮楠生物碱的结构研究。4个新生物碱分别命名为脱氧交让木碱（dehydroxymacropodumineA）(1), 4,21-脱乙酰-23-脱甲基-脱氧交让木胺（4,21-deacetyl-23-demethyl-deoxyyuzurimine） (2),7-氧杂--脱氧交让木胺（7-oxo-deoxyyuzurimine）(3),和4-乙酰氧-虎皮楠素B （4-acetoxydaphmanidinB）(4)。新化合物1-4的结构是通过仔细解析其波谱数据和与已知结构相关的化合物波谱数据比较而确定。脱氧交让木碱（dehydroxymacropodumineA）(1) 具有罕见的11元环的大环内酯结构,是从自然界中分到的第二个具有这一新颖结构特征的生物碱。     

New Labdane‐Type Diterpenoids from Leonurus heterophyllus

Chemical investigation of the aerial part of Leonurus heterophyllus led to the isolation and characterization of the seven labdane‐type diterpenoids 1 – 7 , including six new ones, 1 – 6 . Compounds 4 and 5 were isolated as a C(15) epimer pair. The determination of the structures and relative configurations of the new compounds were mainly based on 1D‐ and 2D‐NMR spectroscopic methods, and comparison of their NMR data with related compounds. The structure of compound 7 was confirmed by X‐ray crystallographic analysis.     

Four New Diterpenoids from Ballota limbata

Six diterpenoids ( 1 – 6 ) belonging to the clerodane and tetracyclic diterpene types were isolated from the CHCl₃ extract of Ballota limbata. The structures of the new compounds 1 and 4 – 6 (named ballatenolide A and limbatenolides A–C, resp.) were established by their spectral data, and their relative configuration was determined by 2D NMR. Compounds 2 and 3 were identified as known clerodanes. Compound 1 had a unique feature, i.e., an α,β‐unsaturated γ‐lactone moiety at C(4)/C(6), whereas limbatenolides A–C ( 4 – 6 ) belonged to the rare class of tetracyclic diterpenoids, which are known to occur only in the genus Ballota. All of the isolated compounds showed inhibitory potential in a cholinesterase‐inhibition assay.     

Terpenoids from the Stems of Drypetes congestiflora

Two new eremophilane‐type sesquiterpenoids, 1α‐hydroxyeremophila‐6,9,11‐trien‐8‐one ( 1 ), 4α‐hydroxyeremophila‐1,9‐diene‐3,8‐dione ( 2 ), and a new friedelane‐type triterpenoid, friedelane‐3α,16β‐diol ( 4 ), along with six known terpenoids, 3 and 5 – 9 , have been isolated from the stems of Drypetes congestiflora. Their structures and relative configurations were elucidated on the basis of detailed spectroscopic analyses and by comparison of their NMR data with those reported in the literature. All of the compounds, 1 – 9 , were isolated for the first time from this species. Compound 3 exhibited moderate cytotoxic activities against the A549 and B16F10 cell lines.     

Squadinorlignoside: A Novel 7,9′‐Dinorlignan from the Stems of Annona squamosa

Two new polar lignans, i.e., squadinorlignoside (= 4‐[(1E)‐1‐(hydroxymethyl)‐3‐(4‐hydroxyphenyl)prop‐1‐en‐1‐yl]phenyl β‐D ‐glucopyranoside; 1 ) and (6R,7R,8S)‐7a‐[(β‐D ‐glucopyranosyl)oxy]‐1‐methoxyisolariciresinol ( 2 ) were isolated from the stems of Annona squamosa, together with eight known lignans and five known neolignans (compounds 3 – 15 ; Fig. 1). All of these constituents are reported for the first time from the genus Annona. The structures, absolute configurations, and selected conformational aspects of the new compounds were elucidated spectroscopically. Compound 1 is the first example of a 7,9′‐dinorlignan natural product.     

Two New Pentacyclic Triterpenoids from Centella asiatica

Two new pentacyclic triterpenoids, named centelloside D ( 1 ) and centelloside E ( 9 ), together with the seven known compounds 2 – 8 , were isolated from the whole plants of Centella asiatica. Compound 5 was reported for the first time from this genus. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D ‐ and 2D ‐NMR, and HR‐MS experiments, and by comparison with literature data. Compounds 1 – 4, 6 , and 8 did not show any cytotoxicity against L929 (mouse embryonic fibroblast).     

A New Peroxy‐multiflorane Triterpene Ester from the Processed Seeds of Trichosanthes kirilowii

A new peroxy‐multiflorane triterpene ester, (3α,5α,8α,20α)‐5,8‐epidioxymultiflora‐6,9(11)‐diene‐3,29‐diol 3,29‐dibenzoate ( 1 ), was isolated from the processed seeds of Trichosanthes kirilowii, together with the two known related derivatives 2 and 3 , and the two known steroids 4 and 5 . Compounds 2, 4 , and 5 were isolated from the genus Trichosanthes for the first time. The structure of compound 1 was established by NMR, HR‐MS, and CD analyses. Compounds 1 – 3 were tested for their in vitro cytotoxicity against human‐tumor cell lines (Hela, HL‐60, and MCF‐7) and anti‐inflammatory activity (LPS‐induced B lymphocyte cells) with the MTT method.     

Further Daphniphyllum Alkaloids from the Leaves of Daphniphyllum macropodum Miq.

Five new polycyclic Daphniphyllum alkaloids, macropodumines F ( 1 ) and G ( 2 ), 17‐oxoyuzurimine ( 3 ), and macropodumines H ( 4 ) and I ( 5 ), were isolated from the leaves of D. macropodum Miq ., collected in Sichuan Province, China. The structures and relative configurations of the new compounds – as well as of four known, related alkaloids – were elucidated on the basis of in‐depth spectroscopic and mass‐spectrometric analyses, by chemical derivatization, and by comparison of spectroscopic data with those of known compounds.