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.     

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.     

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.     

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.     

New Sesquiterpene Formamides from the Marine Sponge Axinyssa sp.

Chemical investigation of an extract of the marine sponge Axinyssa sp., collected from the South China Sea, led to the isolation and identification of two new sesquiterpene formamides, (4R*,5R*,10R*)‐4‐formamidoeudesm‐7‐ene ( 1 ) and (4R*,5R*,7S*,10R*)‐4‐formamidoeudesman‐11‐ol ( 2 ), together with the known 4α‐formamidogorgon‐11‐ene ( 3 ). Their structures were elucidated by spectroscopic methods, including 1D‐ and 2D‐NMR spectroscopy, high‐resolution ESI‐TOF mass spectrometry, as well as X‐ray single‐crystal diffraction experiments. Possible biosynthetic pathways for 1 – 3 were also proposed. The human nasopharyngeal cancer cell line CNE‐2, human cervical cancer cell line HeLa, and human normal liver cell line L02 were used to examine the cytotoxic activities of 1 – 3 in vitro. As the results, 1 showed significant cytotoxic activity against CNE‐2, HeLa, and L02 cell lines with the IC₅₀ values of 13.8, 7.5, and 38.0 μg/ml, resp.     

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 α‐Glucosidase Inhibitors from the Mongolian Medicinal Plant Ferula mongolica

The four new and four known sesquiterpenoid derivatives 1 – 4 and 5 – 8 , respectively, were isolated from the air‐dried roots of Ferula mongolica. The structures of these compounds were determined by spectroscopic methods and found to be rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐3,4‐dihydro‐3,8‐dihydroxy‐2‐methyl‐2H,5H‐pyrano[2,3‐b][1]benzopyran‐5‐one ( 1 ), rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethyl‐4H‐furo[2,3‐b][1]benzopyran‐4‐one ( 2 ), rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethyl‐4H‐furo[3,2‐c][1]benzopyran‐4‐one ( 3 ), rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐2,3‐dihydro‐7‐methoxy‐2,3‐dimethyl‐4H‐furo[3,2‐c][1]benzopyran‐4‐one ( 4 ), (4E,8E)‐1‐(2‐hydroxy‐4‐methoxyphenyl)‐5,9,13‐trimethyltetradeca‐4,8,12‐trien‐1‐one ( 5 ), the rel‐(2R,3S) diastereoisomer 6 of 2 , the rel‐(2R,3S) diastereoisomer 7 of 4 , and (4E,8E)‐1‐(2,4‐dihydroxyphenyl)‐5,9,13‐trimethyltetradeca‐4,8,12‐trien‐1‐one ( 8 ). These compounds were tested as inhibitors against the enzyme α‐glucosidase. The compounds 1 – 6 and 8 exhibited significant inhibitory activity and, therefore, represent a new class of α‐glucosidase inhibitors.     

Identification of Three New Flavonoids from the Peels of Citrus unshiu

Three new flavonoids, 5,6,7,8,3′,4′‐hexamethoxyhomoflavone ( 1 ), 5,6,7,8,4′‐pentamethoxyhomoflavone ( 2 ) and 3,6,7,8,2′,5′‐hexamethoxyflavone ( 3 ) were isolated from the peels of mature fruits of Citrus unshiu Marcow (Rutaceae), together with the three known compounds 6,7,8,4′‐tetramethoxyflavone (=6,7,8‐trimethoxy‐2‐(4‐methoxyphenyl)‐4H‐1‐benzopyran‐4‐one), 3,5,7,8,2′,5′‐hexamethoxyflavone (=2‐(2,5‐dimethoxyphenyl)‐3,5,7,8‐tetramethoxy‐4H‐1‐benzopyran‐4‐one), and scopoletin (=7‐hydroxy‐6‐methoxy‐2H‐1‐benzopyran‐2‐one) of which the former two have never been isolated from natural resources, although they have been reported as synthetic compounds. The structures of 1 – 3 were elucidated on the basis of spectroscopic evidence, including 1D‐ and 2D‐NMR analysis.     

A Guaianolide Sesquiterpene,a Chromenone,and a Flavanone from Ligularia macrophylla

Three new compounds, (5β,9β)‐guaia‐6,10(14)‐dien‐9‐ol (=rel‐(1R,3aS,5R,8aR)‐1,2,3,3a,4,5,6,8a‐octahydro‐1‐methyl‐4‐methylene‐7‐(1‐methylethyl)azulen‐5‐ol; 1 ), 6‐acetyl‐8‐methoxy‐2,3‐dimethylchromen‐4‐one (=6‐acetyl‐8‐methoxy‐2,3‐dimethyl‐4H‐1‐benzopyran‐4‐one; 2 ), and (2S)‐3′‐hydroxy‐5′,7‐dimethoxyflavanone (=(2S)‐2,3‐dihydro‐2‐(3‐hydroxy‐5‐methoxyphenyl)‐7‐methoxy‐4H‐1‐benzopyran‐4‐one; 3 ) were isolated from the roots and rhizomes of Ligularia macrophylla, together with seven known compounds. Their structures and configurations were elucidated by spectroscopic methods, including 2D‐NMR techniques.     

New Monoterpene-Substituted Dihydrochalcones from Piper aduncum

Five New unusual monoterpene-substituted dihydrochalcones, the adunctins A–E (1″S)-1-{2′-hydroxy-4′-methoxy-6′-[4″-methyl-1″-(1?-methylethyl)cyclohex-3″ -en-1″ -yloxy]phenyl}-3-phenylpropan-1-one ( 1 ), (5aR*,8R*,9aR*)-3-phenyl-1-[5′,8′,9′,9′a-tetrahydro-3′-hydroxy-1′-methoxy-8′-(1″-methylethyl)-5′-a-methyldibenzo-[b,d]furan-4′-yl]propan-1-one ( 2 ), (2′R*,4″S*)-1-{6′-hydroxy-4′-methoxy-4″-(1?-methylethyl)spiro[benzo[b]-furan-2′(3′H),1″ -cyclohex-2″ -en]-7′-yl}-3-phenylpropan-1-one ( 3 ), (2′R*,4″R*)-1-{6′-hydroxy-4′-methylethyl-4″-(1?-methylethyl)spiro[benzo[b]furan-2′(3′H),1″-cyclohex-2″-en]-7′-yl}-3-phenypropan-1-one ( 4 ), and (5′aR*,6′S*, 9′R*,9′aS*)-1-[5′a,6′,7′,8′,9′a-hexahydro-3′,6′-methoxy-6′-methyl-9′-(1″-methylethyl)dibenzo[b,d]-furan-4′-yl]-3-phenylpropan-1-one ( 5 ) were isolated from the leaves of Piper aduncum (Piperaceae) by preparative liquid chromatography. In addition, (?)-methyllindaretin ( 6 ), trans-phytol, and α-tocopherol ( = vitamin E) were also isolated and identified. The structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The antibacterial and cytotoxic potentials of the isolates were also investigated.     

Furopyridines. XVIII. Photocycloaddition of furo[2,3-c]pyridin-7(6H)-one with acrylonitrile

The photocycloaddition of furo[2,3-c]pyridin-7(6H)-one ( 1 ) and its N-mefhyl derivative ( 1-Me ) to acrylonitrile has been studied. The structures of the photoadducts isolated by colum chromatography were determined by the nuclear magnetic resonance spectroscopy and single crystal X-ray analysis. The cyclo-addition of 1 afforded an adduct 2 at the carbonyl oxygen and 8-cyano-8,9-dihydrofuro[d]azocin-7(6H)-one ( 3 ), and the addition of 1-Me the N-methyl derivative 3-Me of 3 , (9S*)-9-cyano-6-methyl-3a,7a-dihydro-3a,7a-ethanofuro[2,3-c]pyridin-7(6H)-one ( 4 ), (2S*, 2aR*, 7bR*)- ( 5 ) and (1R*, 2aS*, 7bS*)-2-cyano-3-methyl-4-oxo-1,2,2a,3,4,7b-hexahydrocyclobuta[e]furo[2,3-c]pyridine ( 6 ).     

New Lignan,Benzofuran, and Sesquiterpene Derivatives from the Roots of Leontopodium alpinum and L. leontopodioides

Three new compounds, including a benzofuran, 1‐{(2R*,3S*)‐3‐(β‐D ‐glucopyranosyloxy)‐2,3‐dihydro‐2‐[1‐(hydroxymethyl)vinyl]‐1‐benzofuran‐5‐yl}ethanone ( 1 ), a lignan, [(2S,3R,4R)‐4‐(3,4‐dimethoxybenzyl)‐2‐(3,4‐dimethoxyphenyl)tetrahydrofuran‐3‐yl]methyl (2E)‐2‐methylbut‐2‐enoate ( 2 ), and a silphiperfolene‐type sesquiterpene, [(1S,2Z,3aS,5aS,6R,8aR)‐1,3a,4,5,5a,6,7,8‐octahydro‐1,3a,6‐trimethylcyclopenta[c]pentalen‐2‐yl]methyl acetate ( 3 ), together with the known coumarins obliquin ( 4 ) and its 5‐methoxy derivative 5 were isolated from the roots of Leontopodium alpinum. Another known coumarin derivative, 5‐hydroxyobliquin ( 6 ), was isolated from the roots of L. leontopodioides. The structures of these compounds were established by spectroscopic studies.     

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.     

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.     

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.     

Sesquiterpenoids and 2‐(2‐Phenylethyl)‐4H‐chromen‐4‐one (=2‐(2‐Phenylethyl)‐4H‐1‐benzopyran‐4‐one) Derivatives from Aquilaria malaccensis Agarwood

The four new sesquiterpenoids 1 – 4 , and the new 2‐(2‐phenylethyl)‐4H‐chromen‐4‐one (=2‐(2‐phenylethyl)‐4H‐1‐benzopyran‐4‐one) derivative 5 , together with the two known sesquiterpenoids 6 and 7 , the five known chromenones 8 – 12 , and 1‐hydroxy‐1,5‐diphenylpentan‐3‐one ( 13 ), were isolated from a 70% MeOH extract of Aquilaria malaccensis agarwood chips. Their structures were elucidated on the basis of comprehensive spectral analyses and comparison with literature data.     

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.     

Dapholidins A – C,New Isomeric Biisoflavonoids From Daphne oleoides

Three new isomeric biisoflavonoids, dapholidins A–C ( 1 – 3 , resp.), have been isolated from the AcOEt‐soluble fraction of the MeOH‐soluble extract of the roots of Daphne oleoides, along with the known compounds daphwazirin ( 4 ), daphnetin 8‐O‐β‐D ‐glucopyranoside ( 5 ), daphnin ( 6 ), daphneticin 4″‐O‐β‐D ‐glucopyranoside ( 7 ), and 6,7‐dihydroxy‐3‐methoxy‐8‐[2‐oxo‐2H‐1‐benzopyran‐7‐(O‐β‐D ‐glucopyranosyl)‐8‐yl]‐2H‐1‐benzopyran‐2‐one ( 8 ). The structures of the new compounds were determined by spectroscopic analyses, including 1D‐ and 2D‐NMR.     

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.