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 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.     

Diels–Alder adducts of medium-ring carbocyclic dienes prepared by rearrangement of catalytically generated cyclic oxonium ylides

The novel bicyclic and tricyclic systems di­methyl (4aS*,6S*)-6-methoxy-7-oxo-4a,5,6,7,8,9-hexa­hydro-2H-benzo­cyclo­hept­ene-3,4-di­carboxyl­ate, C₁₆H₂₀O₆, (I), di­methyl (4aS*,6R*)-6-methoxy-7-oxo-4a,5,6,7,8,9-hexa­hydro-2H-benzo­cyclo­hept­ene-3,4-di­carboxyl­ate, C₁₆H₂₀O₆, (II), (3aS*,9R*,10aS*,10bR*)-9-methoxy-2-oxa-1,3a,4,6,7,8,9,10,10a,10b-deca­hydro-3H-cyclo­hepta­[e]­indene-1,3,8-trione, C₁₄H₁₆O₅, (III), and (1S*,2R*,9S*,10aR*)-9-methoxy-8-oxo-1,2,3,5,6,7,8,9,10,10a-deca­hydrobenzo­cyclo­octene-1,2-di­carboxyl­ic acid, C₁₅H₂₀O₆, (IV), have been crystallographically characterized, allowing the determination of the relative configuration of the stereogenic centres. The poor quality of the di­carboxyl­ic acid crystals necessitated the use of synchrotron radiation.     

Enantioselective syntheses of isoprostane and iridoid lactones intermediates by enzymatic transesterification

Crude Pseudomonas cepacia lipase (Amano PS-30) is a suitable biocatalyst for the kinetic resolution of the 1,2-cis-disubstituted cyclopentanoid building block (3aR*,4R*,6aS*)-(±)-4-hydroxymethyl-3,3a,4,6a-tetrahydrocyclopenta[b]furan-2-one through enantioselective transesterification. Enantiomerically enriched acetic acid (3aS,4S,6aR)-(+)-2-oxo-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-4-yl methyl ester was utilized in a formal synthesis of the iridoids (+)-isoiridomyrmecin and (−)-teucriumlactone.     

Synthesis of 1′-substituted and 1′,3′-disubstituted (±)-2R*, 11bS*-9,10-Dimethoxy-1,3,4,6,7,11 b-Hexahydrospiro-[benzo[a]quinolizin-2,5′-imidazolidine]-2′,4′-diones

The results of the reaction between (±)-2R*,11bS*-2-alkyl(aryl)amino-1,3,4,6,7,11b-hexahydrobenzo[a]-quinolizine-2-carbonitriles 2 and isocyanates under a variety of experimental conditions are discussed. The ureides 3 and iminohydantoins 4 thus obtained were used to prepare N₃-monosubstituted and N₁,N₃-disubstituted derivatives of the (±)-2R*,11bS*-9,10-dimethoxy-1,3,4,6,7,11b-hexahydrospiro[benzo[a]quinolizin-2,5′-imidazolidine]-2′,4′-dione system 1 . The stereochemistry of these compounds is discussed, on the basis of spectroscopic evidence and study of their chemical reactivity.     

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.     

Synthetic transformations of methylenelactones of eudesmanic type. Behavior of isoalantolactone under the conitions of heck reaction

By Heck reaction of isoalantolactone with aryl bromides or aryl iodides (3aR,4aS, 8aR,9aR,E)-3-arylmethylidene-8a-methyl-5-methylidenedecahydronaphtho[2,3-b]furan-2(3H)-ones and (4aS,8aR,9aS)-3-arylmethyl-8a-methyl-5-methylidene-4a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2(4H)-ones, products of the double bond shift, were synthesized. The yields of the arylation products depend on the nature of the catalytic system and on the structure of the aryl halide. The structures of (3aR,4aS,8aR,9aR,E)-3-(3,4-dimethoxybenzylidene)-8amethyl-5-methylidenedecahydronaphtho[2,3-b]furan-2(3H)-one and (4aS,8aR,9aS)-3-(2-methylsulfanylbenzyl)-8amethyl-5-methylidene-4a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2(4H)-one were proved by XRD analysis.     

Synthesis of tricyclic isoindoles and thiazolo[3,2-c][1,3]benzoxazines

The thermolysis of (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylic acids in Ac₂O led to novel 3-methylene-2,5-dioxo-3H,9bH-oxazolo[2,3-a]isoindoles and chiral (9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindoles were obtained on FVP. Starting from l-cysteine methyl ester (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo[3,2-c][1,3]benzoxazines were obtained as single stereoisomers. The thermolysis of (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo[3,2-c][1,3]benzoxazine-3-carboxylic acid in Ac₂O gave 5-acetyl-2-phenyl-2,3-dihydrothiazole. The structures of methyl (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylate 1a and methyl (2R,4R)-N-chlorocarbonyl-2-(2-hydroxyphenyl)thiazolidine-4-carboxylate 9 were determined by X-ray crystallography.     

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.     

N-Trifluoroacetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline ozonides

A three-component condensation of aromatic amine, aldehyde, and cyclopentadiene with subsequent N-trifluoroacetylation leads to 4- and 4,8-substituted N-trifluoroacetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines. Ozonation of the double bond in the latter produced the corresponding isomeric stable ozonides having (1R*,4S*,5aR*,6S*,11bR*)-configuration and differing in inversion at the carboxamide nitrogen atom.     

Novel cembranolides (Coralloidolide D and E) and a 3,7-Cyclized cembranolide (Coralloidolide C) from the mediterranean coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (= Parerytkropodium) coralhides (PALLAS, 1766) is shown to contain three novel diterpenes which are of biogenetic significance: the 3,7-cyclized cembranoid Coralloidolide C ( = (+)-(6R*, 7R*, 11S*, 12aS* 3aE)-7,8-epoxy-3,5,6,7,8,9,10,11,12,12a-decahydro-12a-hydroxy-11-isopropenyl-1,4-dimethyl-3-oxocyciopentacydoundecene-8,6-carbolactone; (?)- 3 ), the O-bridged diketonic cembranolide Coralloidolide D (= (+)-(1R*, 2S*, 3R*, 5R*, 12S*, 8Z)-2,5-epoxy-1-hydroxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetradeca-8-ene-1,3-carbolactone; (+)- 4 ), and the diketonic epoxycembranolide coralloidolide E (=(+)-(1R*, 2R*, 3R*, 12S*, 5Z, 8Z)-1,2-epoxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetra-deca-5,8-diene-1,3-carbolactone; (+)- 5 ), The latter in pyridine at r. t. undergoes a double bond shift from C(4) = C(5) to C(4) = C(18) to give the isomer (?)- 7 . Structural assignments are mainly based on ID and 2D NMR and MS spectral data. Either corailoidolide A ((?)- 1 ) or the hypothetic unsaturated 1,4-diketone 9 can be envisaged as the precursors of all coralloidolides.     

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 .     

Functionalized 2-azabicyclo[3.3.1]nonanes. III.1 reductive rearrangement of an hexahydro-2-oxopyrano[3,2-b]pyridine

Reduction of 5-benzoyl-8-methyl-2-oxo-3,4,4a,5,6,7-hexahydro-2H-pyrano[3,2-b] pyridine ($\text{1}$) with lithium aluminium hydride afforded (1R^*,5S^*,6R^*,9S^*)-2-benzyl-5-methyl-2-azabicyclo[3.3.1]nonane-6,9-diol ($\text{2}$).     

Regioselectivity in the formation of norbornene-fused pyrazoles: preparation of 1-substituted derivatives of 4,5,6,7-tetrahydro-1H-4,7-methanoindazole

The structural characteristics of (±)-(exo,exo)-3-(hydroxymethylene)-5,6-(isopropylidenedioxy)bicyclo[2.2.1]heptan-2-one make the reactions between this β-diketone and hydrazines particularly interesting for elucidating the mechanism of pyrazole formation. The isolation and X-ray structure determination of two 5-hydroxy substituted Δ²-pyrazolines [(±)-(3aR*,4R*,5R*,6S*,7R*,7aR*)-7a-hydroxy-5,6-(isopropylidenedioxy)-3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indazole] and [(±)-(3aS*,4R*,5R*,6S*,7R*,7aR*)-7a-hydroxy-5,6-(isopropylidene-dioxy)-1-phenyl-3a,4,5,6,7,7a-hexa-hydro-4,7-methano-1H-indazole] has been determinant for proposing a mechanism. Besides B3LYP/6-31G* calculations have been carried out on all intermediate dihydroxypyrazolidines and 5-hydroxypyrazolines. Finally, the annular tautomerism of the NH-methanotetrahydroindazoles has been studied both experimentally (¹³C NMR) and theoretically: the Mills-Nixon effect favours the 2H-tautomer.     

Synthesis of substituted cyclopentanes based on intramolecular [3+2] cycloaddition of trimethylsilyl nitronates generated from 6-nitrohex-1-ene derivatives

A method for the stereoselective synthesis of substituted 4aS*,7aS*-hexahydrocyclopenta[c]pyran-3(1H)-one, promising synthon of isoprostanes, has been developed based on the intramolecular dipolar [3+2] cycloaddition of silyl nitronates generated from 6-nitrohex-1-ene derivative.     

Efficient synthesis of new tricyclic pyrano[3,2-c]pyridine derivatives

Reaction between arylidenemalononitriles and acetoacetanilide in the presence of piperazine hydrate in methanol at room temperature affords new tricyclic pyrano[3,2-c]pyridine derivatives of (rac-1S*,2R*,3R*,7R*,8R*,11R*)-2,11-diaryl-4,10-diimino-8-methyl-5-phenyl-6-oxo-9-oxa-5-azatricyclo-[5.3.1.0^3,8]undecane-1,3-dicarbonitrile family in yields of 55–84%. The molecular structures of the products were confirmed by X-ray crystallography and NMR spectroscopy.     

Synthesis of novel tricyclic isoindole derivatives

Novel 3-methylene-2,5-dioxo-3H,9bH-oxazolo[2,3-a]isoindoles were prepared from the thermolysis of (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylic acids in acetic anhydride. The structure of 3-methylene-2,5-dioxo-3H,9bH-oxazolo[2,3-a]isoindole 6a was determined by X-ray crystallography.     

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.     

Synthesis of (5R*)- and (5S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-ones

Heating of N-benzoyl-N-[2-(1-methylbut-2-en-1-yl)-4-methylphenyl]glycine with ethyl chloroformate or acetic anhydride gave (5R*) and (5S*) isomers of (1R*,3aS*,4S*,11S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one.     

Adriadysiolide,the First Monoterpenoid Isolated from a Marine Sponge

Spectra and chemical transformations allow to establish the gross structure 6,7-epoxy-4,7-dimethyl-l-oxa-spiro[4.4]non-3-en-2-one for adriadysiolide ( 1 ), the first monoterpenoid isolated from a marine sponge, a Dysidea sp. of the Adriatic Sea. Its configuration 5R*, 6S*, 7S* as given in 1a is derived from diastereoselective total syntheses of both 1a and its diastereoisomer 1b via stereochemically predictable peracid epoxidations of olefinic precursors. Thus, OH assistance in allylic alcohol 8 leads to oxirane 13 which is subjected to methyl cuprate conjugate addition to give epiadriadysiolide ( 1b ), whilst electronic deactivation by a neighboring heterocyclic O-atom in intermediate 5 , derived from 8 mainly leads to adriadysiolide ( 1a ). Comparative ¹H-NMR shift-reagent effects with 1a and 1b , evaluated with the aid of molecular-mechanics calculations, support these conclusions.