A New Isofuranonaphthalenone and Benzopyrans from the Endophytic Fungus Nodulisporium sp. A4 from Aquilaria sinensis

A new isofuranonaphthalenone, (7R*,8S*)‐3,6,7,8‐tetrahydro‐4,7,8‐trihydroxynaphtho[2,3‐c]furan‐5(1H)‐one ( 1 ), and a new benzopyran, (2R*,4R*)‐3,4‐dihydro‐4‐methoxy‐2‐methyl‐2H‐1‐benzopyran‐5‐ol ( 2 ), together with four known related analogs, 3 – 6 , were isolated from the culture of Nodulisporium sp. A4, an endophytic fungus from the stem of Aquilaria sinensis (Lour.) Gilg . The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature reports. The isolated compounds 1 – 6 were evaluated for their cytotoxic activities against the NCI‐H460 and SF‐268 tumor cell lines.     

Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

Two New 7‐Dehydrobrefeldin A Acids from Cylindrocarpon obtusisporum,an Endophytic Fungus of Trewia nudiflora

Two new 7‐dehydrobrefeldin A acids, (2E,4R*)‐4‐hydroxy‐4‐{(1R*,2S*)‐4‐oxo‐2‐[(1E)‐6‐oxohept‐1‐en‐1‐yl]cyclopentyl}but‐2‐enoic acid ( 3 ) and (2E,4R*)‐4‐hydroxy‐4‐{(1R*,2S*)‐2‐[(1E,6S*)‐6‐hydroxyhept‐1‐en‐1‐yl]‐4‐oxocyclopentyl}but‐2‐enoic acid ( 4 ), were isolated from the endophytic fungal strain Cylindrocarpon obtusisporum (Cooke & Harkness ) Wollenw . of Trewia nudiflora, together with two known compounds, 7‐dehydrobrefeldin A ( 2 ) and brefeldin A ( 1 ). Their structures were determined on the basis of extensive 1D‐ and 2D‐NMR‐spectral analysis.     

Acetogenins from the Leaves of Rollinia laurifolia

From the EtOH extract of the leaves of Rollinia laurifolia Schl . (Annonaceae), a novel acetogenin, rolifolin (= 3‐(9‐{(2R*,5S*)‐5‐[(1S*,4S*)‐1,4‐dihydroxy‐4‐{(2S*,5R*)‐5‐[(1S*)‐1‐hydroxyundecyl]tetrahydrofuran‐2‐yl}butyl]tetrahydrofuran‐2‐yl}‐2,3‐dihydroxynonyl)‐5‐methylfuran‐2(5H)‐one; 1 ) was isolated, together with the known acetogenin annonin‐I ( 2 ). Also, from the corresponding hexane extract, a mixture of rolilaurin ( 3 , a novel compound), uvariamicin‐I ( 4 ), and uvariamicin‐II ( 5 ) was obtained. The structures of compounds 1 – 5 were elucidated by NMR and MS analysis, and relative configurations were established. Compounds 2 and 5 have never been obtained before from Rollinia.     

Bisabolane Derivatives from Leontopodium alpinum

From the roots of Leontopodium alpinum, four new bisabolane sesquiterpenoids, (1R*,2S*,4R*,5S*)‐4‐(acetyloxy)‐2‐[3‐(acetyloxy)‐1,5‐dimethylhex‐4‐enyl]‐5‐methylcyclohexyl (2Z)‐2‐methylbut‐2‐enoate ( 1 ), (1R*,4S*,6R*)‐4‐(acetyloxy)‐6‐[3‐(acetyloxy)‐1,5‐dimethylhex‐4‐enyl]‐3‐methylcyclohex‐2‐en‐1‐yl (2Z)‐2‐methylbut‐2‐enoate ( 2 ), and 3‐methyl‐1‐{2‐[(1R*,2R*,5R*,6S*)‐2,5,6‐tris(acetyloxy)‐4‐methylcyclohex‐3‐en‐1‐yl]propyl}but‐2‐enyl (2Z)‐2‐methylbut‐2‐enoate ( 3 and 4 ) have been isolated. The latter constituents differ from each other by the relative configurations of the chiral centers of the hexenyl side chain.     

Two New Ceramides from the Marine Sponge Ircinia fasciculata

A new 4‐sulfated ceramide, ircisulfamide (=N‐[(1S*,2S*,3R*)‐2‐hydroxy‐1‐(hydroxymethyl)‐3‐(sulfooxy)heptadecyl]hexadecanamide; 1 ), and a new glycosphingolipid, ircicerebroside (=(2R*)‐N‐{(1S*,2R*,3E,7E)‐1‐[(β‐D ‐glucopyranosyloxy)methyl]‐2‐hydroxy‐8‐methylheptadeca‐3,7‐dienyl}‐2‐hydroxyeicosanamide; 2 ), were isolated from the aqueous EtOH extract of the marine sponge Ircinia fasciculata (Pallas ). The structures of the new compounds were elucidated on the basis of spectroscopic analysis and by means of chemical methods.     

New Sesquiterpenoids from Salvia castanea Diels f. tomentosa

Two new sesquiterpenoids, castanin A (= 4R*,5R*,5aS*,8S*,8aR*,8bR*)‐8‐formyl‐4,5,5a,6,7,8,8a,8b‐octahydro‐5,8b‐dihydroxy‐3,5a,8‐trimethyl‐2‐oxo‐2H‐indeno[4,5‐b]furan‐4‐yl acetate; 1 ) and castanin B (= 1aS*,6R*,6aS*,7aR*,9aR*)‐1a,2,6,6a,7a,8,9,9a‐octahydro‐1a,5,7a‐trimethylbisoxireno[4,5 : 8,9]cyclodeca[1,2‐b]furan‐6‐yl acetate; 2 ) were isolated from the aerial parts of Salvia castanea Diels f. tomentosa, together with two known compounds, oplophanone and 1β,6α‐dihydroxyeudesm‐4(14)‐ene. Their structures were elucidated by spectroscopic analyses and, in the case of 2 , also by X‐ray crystallography. Castanin A ( 1 ) represents a novel sesquiterpenoid, with a contracted ring A, derived from eudesmanolide. A possible biogenetic pathway is proposed.     

A convenient and diastereoselective route to homoallyl alcohols: Addition of (z)- or (e)-alkenyl-dimethoxyboranes to aldehydes

(Z)-2-Butenyl-dimethoxyborane adds smoothly to propanal and benzaldehyde to afford the homoallyl alcohols (R*,R*)- 1 and (R*,R*)- 2 , In contrast (E)-2-butenyl-dimethoxyborane leads to adducts having the (R*,S*)-configuration. Dimethoxy-(Z)-2-pentenylborane, dimethoxy-(Z)-(2-methyl-2-butenyl)borane and (2Z,4E)-or (2E,4Z)hexadienyl-dimethoxyborane, treated with propanal, give (R*,R*)- 3 , (R*,R*)- 4 , (E),(R*,S*)- 5 and (Z),(R*, R*)- 5 , respectively. A transition state model implying a pericyclic electron motion is in perfect agreement with the regio- and stereoselective outcome of these borane reactions.     

A Novel Dimeric Podophyllotoxin‐Type Lignan and a New Withanolide from Withania coagulans

A novel dimeric lignan, bispicropodophyllin glucoside ( 1 ) and a highly oxygenated new withanolide, coagulin S ( 2 ) were isolated from the ethanolic extract of Withania coagulans. The structures were established on the basis of the spectroscopic data and have been identified as (5S*,5aR*,8aR*,9S*,15S*,15aS*,18aS*,19S*)‐9,19‐di‐β‐D ‐glucopyranosyl‐5,8a,9,15,15a,18,18a,19‐octahydro‐5,15‐bis(3,4,5‐trimethoxyphenyl)bis([1,3]dioxolo[4′,5′:6,7]naphtho)[2,3‐c:2,3‐h][1,6]dioxecin‐6,16(5aH,8H)‐dione ( 1 ) and (20S*,22R*)‐5α,6β,14α,15α,17β,20,27‐heptahydroxy‐1‐oxowith‐24‐enolide ( 2 ), respectively.     

Coralloidin C,D, and E: Novel Eudesmane Sesquiterpenoids from the Mediterranean Alcyonacean Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (=Parerythropodium) coralloides (Pallas, 1766) is shown to contain the novel eudesmane sesquiterpenoids coralloidin C (=(–)?(4R,10S)-eudesma-5,7(11)-dien-15-yl acetate; (–)? 4 ), coralloidin D (=(–)?(10R*)-eudesma-4,7(11)-diene-12,13-diyl diacetate; (–)? 7 ), and coralloidin E (=(+)?(4R*,10R*)-eudesma-5,7-dien-11-ol;(+)? 8 ). The absolute configuration of (–)? 4 is derived by the exciton-coupling method, applied to deacetylcoralloidin C_p-anisate ((–)? 6 ). Coralloidin E((+)? 8 ), being also obtained on treatment of deacetylcoralloidin A (=(+)?(4R*, 8R*, 10R*)-eudesma-5,7(11)-dien-8-ol; (+)? 2 ) with (COCl)₂ in DMSO, is configurationally correlated to coralloidin A (=(+)?(4R*, 8R*, 10R*)-eudesma-5,7(11)-dien-8-yl acetate; (+)? 1 ). Under acidic conditions, (+)? 2 undergoes a complex rearrangement giving (+)-(3R*, 4S*, 5R*, 6R*, 7S*)-arist-10-(1)-en -3-ol ((+)? 9 ), which is also obtained, together with (+)? 8 , on attempts to mesylate (+)? 2 .     

Packing in three cyclooctitol acetates

Three cyclooctitol derivatives, in the form of a tetraacetate, (1S*,2R*,3S*,4S*)‐2,3,4‐triacetoxycyclooctan‐1‐ylmethyl acetate, C₁₇H₂₆O₈, and two regioisomeric acetonide triacetates, (3aS*,4R*,8S*,9S*,9aS*)‐8,9‐diacetoxy‐2,2‐dimethylcyclooctano[d][1,3]dioxan‐4‐ymethyl acetate and (3aS,4R,7S,9R,9aS)‐7,9‐diacetoxy‐2,2‐dimethylcyclooctano[d][1,3]dioxan‐4‐ylmethyl acetate, both C₁₈H₂₈O₈, have been studied. The conformation of the cyclooctane ring in the three compounds is quite close to the boat–chair form of the parent hydrocarbon. Packing is effected through weak C—H...O and van der Waals contacts.     

Applications of Aziridinium Ions: Selective Syntheses of Pyrazolidin‐3‐ones and Pyrazolo[1,2‐a]pyrazoles

Reaction of ethyl (2S*,3R*)‐3‐chloro‐2‐(dialkylamino)‐3‐phenylpropanoates ( 4 ) with hydrazine monohydrate gave pyrazolidin‐3‐ones ( 5 ) via selective opening of the in situ generated aziridinium ions, followed by intramolecular amidation. (1Z,4S*,5S*)‐1‐Arylmethylidene‐4‐(dialkylamino)‐3‐oxo‐5‐phenylpyrazolidinium‐1‐ide ( 6 ), prepared from pyrazolidin‐3‐ones ( 5 ) and aromatic aldehydes under acid catalysis, reacted with a variety of 1,3‐dipolarophiles to afford good yields of pure cycloadducts 7 – 11 . The cycloaddition regio‐ and/or stereoselectivities, in all relevant cases, were also high.     

Three New Diterpenoids from Isodon nervosus

Three new ent‐kaurane diterpenoids, rabdonervosins D–F ( 1 – 3 ), were isolated from the leaves and stems of Isodon nervosus. Their structures were elucidated on the basis of spectroscopic methods including 1D‐ and 2D‐NMR analyses. Compounds 1 – 3 were evaluated for their cytotoxicity against HepG2, CNE2, PC‐9/ZD, HeLa, MCF‐7, and HCT116 cell lines. No compounds exhibited potent cytotoxicity.     

Aromastoffe der roten Passionsfrucht. Zwei neue Edulanderivate

Aroma Constituents of the Purple Passion Fruit. Two New Edulan Derivatives The isolation of (2R*, 4S*, 4aS*, 8aS*)-4,4a-epoxy-4,4a-dihydroedulan ( 1 ), and (2R*, 3S*, 8aS*)-3-hydroxyedulan ( 2 ), two new constituents of the purple passion-fruit (Passiflora edulis SIMS ), is reported. Racemic epoxide 1 was synthesized by oxidation of edulan 6 with peracidic acid, and racemate of alcohol 2 was obtained by reduction of ketone 7 , one of the chromic acid oxidation-products of edulan 6 .     

The Synthesis of a Novel Epoxycyclohexane from the Fungus Eutypa lata (Pers: F.) TUL

The synthesis of the novel (1′R*,2′S*,3′R*, 4′S*,5′R*)-1-(3′,4′-epxoy-2′, 5′-dihydroxycyclohexyl)-3-methyl-but-2-enone ( 2 ), recently isolated from the culture medium of the fungus Eutypa lata, is described.     

Coralloidolide F,the First Example of a 2,6-Cyclized Cembranolide: Isolation from the Mediterranean Alcyonacean Coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium ( = Parerythropodium) coralloides (Pallas, 1766) is shown here to contain coralloidolide F ( = (+)-(3a-R*, 7R*, 8R*, 9R*, 12R*, 12aS*)-8,9-epoxy-1,3a,6,7,8,9,10,11,12,12a-decahydro-3a-hydroxy-12-isopropenyl-2,5-dimethyl-1-oxocyclopfintacycloundecene-9,7-carbolactone; (+)- 2 ), the first example of a 2,6-cyclized cembranolide. Structural assignments are mainly based on ID and 2D NMR and MS data.     

Modulating the preferred O—H...O hydrogen‐bonding motif in a conformationally constrained environment through hydroxy‐group derivatization

The crystal structures of three conformationally locked esters, namely the centrosymmetric tetrabenzoate of all‐axial perhydronaphthalene‐2,3,4a,6,7,8a‐hexaol, viz.trans‐4a,8a‐dihydroxyperhydronaphthalene‐2,3,6,7‐tetrayl tetrabenzoate, C₃₈H₃₄O₁₀, and the diacetate and dibenzoate of all‐axial perhydronaphthalene‐2,3,4a,8a‐tetraol, viz. (2R*,3R*,4aS*,8aS*)‐4a,8a‐dihydroxyperhydronaphthalene‐2,3‐diyl diacetate, C₁₄H₂₂O₆, and (2R*,3R*,4aS*,8aS*)‐4a,8a‐dihydroxyperhydronaphthalene‐2,3‐diyl dibenzoate, C₂₄H₂₆O₆, have been analyzed in order to examine the preference of their supramolecular assemblies towards competing inter‐ and intramolecular O—H...O hydrogen bonds. It was anticipated that the supramolecular assembly of the esters under study would adopt two principal hydrogen‐bonding modes, namely one that employs intermolecular O—H...O hydrogen bonds (mode 1) and another that sacrifices those for intramolecular O—H...O hydrogen bonds and settles for a crystal packing dictated by weak intermolecular interactions alone (mode 2). Thus, while the molecular assembly of the two crystalline diacyl derivatives conformed to a combination of hydrogen‐bonding modes 1 and 2, the crystal packing in the tetrabenzoate preferred to follow mode 2 exclusively.     

Five-membered 2,3-dioxo heterocycles: LXXVII. [4 + 2]-Cycloaddition of alkyl vinyl ethers to 3-aroylpyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4(4<Emphasis Type="Italic">H</Emphasis>)-triones

[4 + 2]-Cycloaddition of 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4(4H)-triones to alkyl vinyl ethers gave substituted stereoisomeric (1R*,16R*)- and (1S*,16R*)-16-alkoxy-14-aryl-3,15-dioxa-10-azatetracyclo[8.7.0.0^{1, 13}.0^{4, 9}]heptadeca-4,6,8,13-tetraene-2,11,12-triones.     

Novel Trinor-eremophilanes (Dendryphiellin B,C, and D), Eremophilanes (Dendryphiellin E,F, and G), and Branched C9-Carboxylic Acids (Dendryphiellic Acid A and B) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

Further investigation of global extracts from cultures of the marine deuteromycete Dendryphiella salina leads to the isolation of three novel trinor-eremophilanes esterified by branched C₉-carboxylic acids, dendryphiellin B (= (+)-(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E, 4E)-6-hydroxy-6-methylocta-2,4-dienoate; (+)- 2 ), dendryphiellin C (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7,8,8a-hexa-hydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S, 2E, 4E)-6-methylocta-2,4-dienoate; (+)- 3 )), and dendryphiellin D (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7(8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*,2E,4E)-6-(hydroxymethyl)octa-2,4-dienoate; (+)- 4 ). An intact eremophilane, dendryphiellin E ( 5 ), and its ethanolysis product dendryphiellin F whose absolute configuration is represented by structural formula (+)- 6 are also isolated from the above extracts. Dendryphiellin E exists as an open form 5a in equilibrium with a closed form 5b . A similar equilibrium exists between the open form 8a and the closed form 8b of a non-esterified eremophilane, dendryphiellin G ( 8 ), which is isolated too from the above extracts and proves structurally related to the cyclic portion of 5 . Finally, the free, branched C₉-carboxylic acids dendryphiellic acid A ((+)- 9 ) and B ((+)- 10 ) which correspond to side chains of the above esterified terpenes are also isolated from the above extracts.     

Five New Cycloartane‐Type Triterpenoid Saponins from Nervilia fordii

Five new cycloartane glycosides, nervisides D–H ( 1 – 5 ), were isolated from the AcOEt‐ and H₂O‐soluble portions of the 90% EtOH extract of the aerial part of the plant Nervilia fordii. The structures of the isolated glycosides were elucidated by extensive spectroscopic analysis including HR‐ESI‐MS and NMR data. The isolated nervisides D–H were evaluated for the cytotoxic activity in vitro against human‐tumor cell lines (CNE, Hep‐2 and HepG2) with the MTT method.