Showing papers on "Enone published in 1996"
TL;DR: In this paper, a general approach to the synthesis of a new class of LTD4 antagonists is presented, based on the diarylpropane framework, which is prepared by Claisen−Schmidt condensation and selective reduction of the enone.
Abstract: A general approach to the synthesis of a new class of LTD4 antagonists is presented. The key diarylpropane framework was prepared by Claisen−Schmidt condensation and selective reduction of the enone. Depending on the bridge to the 7-chloroquinaldine moiety, alkylation or Heck coupling methodology was developed. The chiral sulfides were introduced by asymmetric reduction of the diarylpropanone intermediates and subsequent inversion of the chiral center.
206 citations
TL;DR: In this article, the tricyclic enone 2 was constructed via an intramolecular [4 + 2] cycloaddition, as schematized in Figure 1.
Abstract: It has been said that the active components in the Digitalis extracts have been “the most ingested drugs in medicine”.1 These substances, usually called cardenolides, differ from ordinary steroids in three major respects: the C/D ring system is cis rather than trans fused, there is a tertiary hydroxyl at C-14, and the substituent at C-17 (a butenolide) is in the thermodynamically less stable â orientation.2 As might be expected, many partial syntheses of cardenolides have been described starting with readily available steroids.3,4 We now report the total synthesis of natural (+)-digitoxigenin (1), the biologically active cardenolide which, as its trisaccharide derivative digitoxin, is one of the most frequently used of the active principles isolated from Digitalis species. We divided the synthesis, which we carried out both to racemic and to natural (+)-digitoxigenin, in three parts: synthesis of the tricyclic enone 2; elaboration of the fused 5-membered ring D to produce a tetracyclic system bearing both a 14-â-hydroxy substituent and a substituent at C-17 capable of further transformation; and, finally, elaboration of that substituent to the â-oriented butenolide system. We chose to approach the construction of the tricyclic enone 2 via an intramolecular [4 + 2] cycloaddition, as schematized in Figure 1. We initiated the synthesis from the monoketal (-)-3, prepared by applying to the readily available (S)-enantiomer of the Wieland Miescher ketone,5 the sequence previously described6 using its racemate. Ozonolysis of the trimethylsilyl enol ether of 3 gave, in a not unprecedented reaction,7 a mixture of R-hydroxy ketones which was reduced (NaBH4) to the corresponding glycols, followed by cleavage with periodate to the dialdehyde 4 (71% overall yield from 3). The two aldehyde groups in 4 now had to be differentially elaborated.
78 citations
TL;DR: In this article, the effect of six-membered ring formation, the presence of a carbonyl group in the tether, and the steric hindrance of the alkene conspire to prevent the cycloisomerization under the standard conditions.
Abstract: The scope of the palladium catalyzed cycloisomerization of enynes in an Alder ene type fashion that led to a new catalytic system was explored in the context of a synthetic strategy to the antiulcerogenic agent (+)-cassiol. In a model study, the effect of six-membered ring formation, the presence of a carbonyl group in the tether, and the steric hindrance of the alkene conspire to prevent the cycloisomerization under the “standard” conditions. Two variables proved key in the development of a new catalytic system that has proven to be effective, the absence of traditional ligands and the choice of acid. An effective synthesis of (+)-cassiol was accomplished in which this new reaction played a key. A lipase served to introduce the chirality, and a palladium(0) catalyzed reaction was important in elaborating a side chain. The final adjustment of oxidation level made advantageous use of a platinum catalyzed enone hydrosilyation.
74 citations
TL;DR: The first cyathin diterpenes were synthesized using a carbonyl ene reaction of 14a to construct an appropriately functionalized seven-membered ring and palladium-catalyzed carbonylation of dienyl triflates as mentioned in this paper.
Abstract: (±)-Allocyathin B2 (2) and (+)-erinacine A (4), the 1-β-d-xyloside of (+)-allocyathin B2, the first cyathin diterpenes to be prepared, have been synthesized using a carbonyl ene reaction of 14a to construct an appropriately functionalized seven-membered ring and palladium-catalyzed carbonylation of dienyl triflates 10 and 39 as key steps. The entire cyathin carbon skeleton is constructed in seven steps, and allocyathin B2 is synthesized in only 17 steps (>5% overall yield) from readily available enone 9.
65 citations
TL;DR: In this paper, a Hanovia 450-W lamp was used to excite a benzene solution of fullerene and enone, with the latter in large excess, and a series of experiments in which the concentration of reagents and reaction time were systematically varied established that adduct formation occurs only upon light absorption by the enones.
Abstract: The photocycloaddition of cyclic enones to C60 is a general reaction. The addition was initially explored using a crown ether-tagged C60 molecule which allows convenient monitoring of the reaction course by electrospray ionization mass spectroscopy (ESI-MS) after complexation with metal ions, usually K+. A Hanovia 450-W lamp was used to excite a benzene solution of fullerene and enone, with the latter in large excess. A series of experiments in which the concentration of reagents and reaction time were systematically varied established that adduct formation occurs only upon light absorption by the enones. Thus, excitation at 532 nm or in the UV range using low enone:C60 ratios did not lead to adduct formation. ESI-MS analysis showed that monoaddition was favored at short irradiation times, and that up to seven enone units could be added to a single fullerene molecule upon longer exposure to light. Competitive experiments using 12 different enones indicated that the best product yields were obtained, in de...
56 citations
TL;DR: The synthesis of a piperidine A-ring precursor to the alkaloid cylindrospermopsin is described, whose structure and stereochemistry were established by X-ray analysis and which was then protected as the silyl ether 26, which was hydroborated at the terminal olefin to produce primary alcohol ester 28.
Abstract: The synthesis of a piperidine A-ring precursor to the alkaloid cylindrospermopsin (1) is described. The initial approach to the A-ring precursor focused on the imino Diels−Alder reaction of diene 8 with ethyl (N-tosylimino)acetate (9) to form the cycloadduct 10 as a single stereoisomer. However, all attempts to convert ester 10 to a requisite diene such as 5 were unsuccessful. An alternative strategy involved the Diels−Alder cycloaddition of N-tosylimine 9 with oxygenated diene 19 under either thermal or Lewis acid-catalyzed conditions to produce a mixture of cis and trans enones 20 and 21. Although the undesired cis-enone 20 was the major product under all reaction conditions, it could be converted to the desired trans enone 21 by acid-catalyzed isomerization. Copper-mediated conjugate addition of vinylmagnesium bromide to cis-enone 20 followed by stereoselective ketone reduction with L-Selectride produced alcohol 23, whose structure was confirmed by X-ray crystallography. Similarly, trans-enone 21 was c...
50 citations
TL;DR: In this article, the gas phase reactions of O 3 with methacrolein and methyl vinyl ketone have been determined from the amounts of cyclohexanone plus cyclo hexanol formed when the reactions were carried out in the presence of sufficient cycloxide to scavenge > 95% of the OH radicals formed.
47 citations
43 citations
TL;DR: In this paper, the first synthesis of a highly functionalized B-homo-C-nor grayanotoxin closely related to kalmanol was reported, and an enantiocontrolled route to the diquinane sector was first developed from (4R)-(+)-tert-butyldimethylsiloxycyclopentenone by taking advantage of the Michael acceptor properties of this enone and an α,β-unsaturated ester subsequently derived from it, viz., 4 → 7 → 8.3.
Abstract: The first synthesis of a highly functionalized B-homo-C-nor grayanotoxin closely related to kalmanol is reported. An enantiocontrolled route to the diquinane sector was first developed from (4R)-(+)-tert-butyldimethylsiloxycyclopentenone by taking advantage of the Michael acceptor properties of this enone and an α,β-unsaturated ester subsequently derived from it, viz., 4 → 7 → 8. These experiments formed the basis for more advanced substitution of the bicyclo[3.3.0]octane core. In fact, ready access was gained to the α-hydroxy esters 24−27. In these advanced intermediates, it is imperative that the acetyl and carbomethoxy groups bear a trans 1,3-relationship. The neighboring OR substituent should preferably be larger than methoxy in order to guarantee 100% facial selectivity during the ensuing capture by 1 (as its lithiated derivative). This condensation leads unidirectionally to tricyclic lactones represented by 30 and 31 and sets the stage for implementation of sequential Tebbe olefination and Claisen r...
37 citations
TL;DR: Evidence is presented to show that these 1,6-anhydro sugar-cyclopentadiene adducts do not arise from rearrangement of 4 to isolevoglucosenone (5) followed by cycloaddition but are the result of Lewis acid-catalyzed rearrangements of alkene 4 to acyclic dienophile 12 followed by addition of cyclopentadienes.
Abstract: Treatment of d-glucose-derived alkene 4 with cyclopentadiene in the presence of a Lewis acid results in the formation of cycloaddition products 8−11. Evidence is presented to show that these 1,6-anhydro sugar−cyclopentadiene adducts do not arise from rearrangement of 4 to isolevoglucosenone (5) followed by cycloaddition but are the result of Lewis acid-catalyzed rearrangement of alkene 4 to acyclic dienophile 12 followed by addition of cyclopentadiene. Major cycloadduct 8 has been utilized as a source of the enantiomerically pure carbocycles 14−25 by manipulation of the alkene and ketone functions and cleavage of the 1,6-anhydro bridge. In the absence of diene, alkene 4 undergoes rearrangement to enone 5 in 32% yield. Reaction of 5 with several dienes results only in the formation of “bottom-face” adducts 10, 11, 28, and 29, and conjugate addition of either HN3 or Me3COOH is found to be completely stereoselective to afford 30 and 31, respectively. Subsequent manipulation of azide 30 leads to precursors of...
37 citations
TL;DR: In this article, three new azaphilone derivatives designated falconensins E (5), F (6), and G (7) were isolated from the mycelium of Emericella falconensis.
Abstract: Three new azaphilone derivatives designated falconensins E (5), F (6), and G (7) were isolated from the mycelium of Emericella falconensis, along with falconensins A (1), B (2), C (3), D (4), and H (8), and three hopane-type triterpenes, zeorin (9), hopane-7β,22-diol (10), and hopane-6α,7β,22-triol (11). The structures of 5-7 were confirmed by spectroscopic investigation and chemical correlations. The absolute stereochemistry of falconensins A (1) to G (7) was also established.
TL;DR: In this paper, it was shown that β-pinguisene 5 and pinguisenol 6 can be synthesized by propargyl-silane-terminated cyclizations of enone 11 as the key step.
TL;DR: In this article, the results of the Diels−Alder reactions of 1,3-diphenylisobenzofuran with acryloylferrocene (1), 4-ferrocenyl-3-buten-2-one (2), cinnamoylferserrocenes (3), 3-ferrichenyl-1-phenyl-2propenone (4), chalcone (5), 1-((η6phenyl)tricarbonylchromio)-3-phen
Abstract: The Diels−Alder reactions of 1,3-diphenylisobenzofuran with acryloylferrocene (1), 4-ferrocenyl-3-buten-2-one (2), cinnamoylferrocene (3), 3-ferrocenyl-1-phenyl-2-propenone (4), chalcone (5), 1-((η6-phenyl)tricarbonylchromio)-3-phenyl-2-propenone (6), 1-phenyl-3-((η6-phenyl)tricarbonylchromio)-2-propenone (7), and (2-nitrovinyl)ferrocene (8) were examined under various conditions. The best results were achieved using SiO2 and a very acidic montmorillonite clay, KSF, as the catalyst, and the reactions were carried out without solvent. Reasonable to good yields of the Diels−Alder (D-A) products were isolated in most cases. X-ray structural studies showed that the adducts 13b and 13h, derived from the (E)-alkenes 2 and 8, have exo-acetyl or -nitro substituents and endo-ferrocenyl groups with respect to the bridging oxygen atom of the 7-oxabicycloheptane ring system. The product 13a from the monosubstituted enone 1 also has an exo-acyl (ferrocenylcarbonyl) group. Aluminum chloride was found to be a good catal...
TL;DR: In this article, a general approach to the synthesis of a new class of LTD4 antagonists is presented, based on the diarylpropane framework, which is prepared by Claisen−Schmidt condensation and selective reduction of the enone.
Abstract: A general approach to the synthesis of a new class of LTD4 antagonists is presented. The key diarylpropane framework was prepared by Claisen−Schmidt condensation and selective reduction of the enone. Depending on the bridge to the 7-chloroquinaldine moiety, alkylation or Heck coupling methodology was developed. The chiral sulfides were introduced by asymmetric reduction of the diarylpropanone intermediates and subsequent inversion of the chiral center.
TL;DR: In this paper, the major diastereomers were assigned as the syn-derivatives, thus differing from diastererofacial selectivity found with nitrile oxides.
Abstract: The cycloaddition reactions of in situ generated silyl nitronates 3 to chiral enone 1a or enoate 1b proceed with high stereoselectivity to give enantiomerically pure N-silyloxyisoxazolidines 4 , which can easily be transformed into Δ 2 -isoxazolines 5 . Based on an X-ray analysis the major diastereomers were assigned as the syn -derivatives, thus differing from diastereofacial selectivity found with nitrile oxides. The base-catalyzed ring-opening reaction of isoxazoline 5a affords the chiral β-hydroxy nitrile 6 , which was cyclized to the sugar-like tetrahydrofuran 7 .
TL;DR: The conjugate additions of the organocopper(I) reagents 22 and 27 to the enantiomerically homogeneous bicyclic enone 4 provided, after epimerization (NaOMe, MeOH) of the resultant product mixtures and appropriate chromatographic separations, the bicyclo[4.3.0]nonan-2-ones 24 and 28 as discussed by the authors.
Abstract: The conjugate additions of the organocopper(I) reagents 22 and 27 to the enantiomerically homogeneous bicyclic enone 4 provided, after epimerization (NaOMe, MeOH) of the resultant product mixtures and appropriate chromatographic separations, the bicyclo[4.3.0]nonan-2-ones 24 and 28. Compounds 24 and 28 were readily converted, via two synthetic steps in each case, into the sesquiterpenoids (−)-homalomenols B (2) and A (1), respectively.
TL;DR: In this article, the chiral bicyclo[2.2] octenones 6, 8 and 9 and 12 and 13 containing a bridgehead methyl group via an intramolecular alkylation reaction were generated.
Abstract: Generation of the thermodynamic dienolate of 9-bromocarvone derivatives 5,7 and 11 furnished the chiral bicyclo[2.2.2]octenones 6, 8 and 9 and 12 and 13 containing a bridgehead methyl group via an intramolecular alkylation reaction. In an analogous manner intramolecular alkylation reaction of the bromo enones 15a–e, obtained from carvone 2 by 1,3-alkylative enone transposition (→14) followed by a regiospecific bromoetherification reaction, furnished the bicyclo[2.2.2]oct-5-en-2-ones 16a–e and 17a–e.
TL;DR: In this paper, high-level ab initio calculations were used to determine the effectiveness of commonly used silanes as Lewis acids toward acrolein as a model for Gilman cuprate conjugate addition reactions.
TL;DR: In this paper, the title cyclopentenone has been prepared by enzymatic resolution of cis -4-phenyloxy- and cis - 4-(4-methoxyphenyloxy)-cyclopent-2-en-1-ol in isopropenyl acetate using Pseudomonas cepacia lipase.
Abstract: The title cyclopentenone has been prepared by enzymatic resolution of cis -4-phenyloxy- and cis -4-(4-methoxyphenyloxy)-cyclopent-2-en-1-ol in isopropenyl acetate using Pseudomonas cepacia lipase. The use of a 4-methoxyphenyloxy-alcohol intermediate enabled the use of both enzymatically resolved enantiomers in the synthesis of the desired (+)-enone.
TL;DR: In this paper, the intermolecular cycloadditions of dienes with 4-phenyl-1,2,4-triazole-3,5(2H)-dione 3 are found to be diastereoselective.
Abstract: Chiral dienes 2, easily prepared from α,β-unsaturated γ-alkoxy ketones, are subjected to inter- and intramolecular Diels–Alder reactions. Intermolecular cycloadditions of dienes 2 with 4-phenyl-1,2,4-triazole-3,5(2H)-dione 3 are found to be diastereoselective. Thermal or high pressure-induced intramolecular cycloadditions of trienes 8, featuring a sulfonate moiety connecting a diene and a dienophile, are found to proceed with high diastereoselectivity to give sultones 11 and 12. An interesting domino process is observed when enone 5 is reacted with sodium hydride. In this reaction sequence, the decahydropyrano[2,3,4-de]chromene derivative 15 was formed. NMR spectroscopic studies allowed the assignments of the configurations of the bi- and tri-cyclic products.
TL;DR: In this article, a mixture of 12-methoxy-7-oxo-8, 11, 13-abietatrien-18-oate and 12-dimethyl-7, 8-dihydro-6H-cyclohepta[b]naphthalene was used to produce enone.
Abstract: Methyl 12-methoxy-7-oxo-8, 11, 13-abietatrien-18-oate (10), prepared from (+)-dehydroabietic acid (9), was rearranged into methyl 7-isopropyl-6-methoxy-1, 10-dimethyl-1, 2, 3, 4-tetrahydroanthracene-1-carboxylate (13) via a series of reaction : dehydrogenation with selenium(IV) oxide, sodium borohydrie reduction, and dehydration with boron trifluoride etherate. Reduction of 13 with lithium aluminum hydride afforded an alcohol (14), which was further reaffanged into 2-isopropyl-3-methoxy-5, 9-dimethyl-7, 8-dihydro-6H-cyclohepta[b]naphthalene (16) by treatment with methanesulfonyl chloride in pyridine. The alcohol 14 was then converted into 7-isopropyl-5, 6-dimethoxy-1, 1, 10-trimethyl-1, 2, 3, 4-tetrahydroanthracene (22) by means of the following reaction : pyridinium chlorochromate oxidation, Huang-Minlon reduction, demethylation, oxidation with Fremy's salt, catalytic hydrogenation, and methylation. Compound 22 was also prepared from methyl 11, 12-dimethoxy-7-oxo-8, 11, 13-abietatrien-18-oate (23) via methyl 7-isopropyl-5, 6-dimethoxy-1, 10-dimethyl-1, 2, 3, 4-tetrahydroanthracene-1-carboxylate (26). Treatment of 22 with DDQ produced an enone (29), which was converted into a diosphenol derivative (31) via a series of reaction : catalytic hydrogenation, and oxidations with Jones reagent and then with oxygen in the presence of potassium tert-butoxide. Demethylation of 31 with ethanethiol and anhydrous aluminum chloride afforded pygmaeocine E (1) and 3, 6-dihydroxy-7-isopropyl-1, 1, 10-trimethyl-1, 2-dihydroanthracen-2-one (32).
TL;DR: In this paper, the cross conjugated α-carbalkoxy enone system was found to be an excellent promoter for polyene cyclization under mild conditions, the reaction occurred efficiently with a high degree of regio-and stereochemical control.
TL;DR: In this paper, the substituted furan carboxaldehyde was converted into enone via a stereoselective intramolecular pyrylium ylide-alkene cyclization.
TL;DR: In this paper, a tricyclic enone-ester derived from 9,10-dibromocamphor was converted to a tricycle enone that may be of value in an enantiospecific synthesis of the limonoids.
TL;DR: In this article, the action of 2-mercaptoacetic acid, thiosemicarbazide and hydrazine hydrate on the titled compound 1 is studied, and the structure of the new heterocycles 2 - 8 is discussed in the light of IR and 1HNMR spectra.
TL;DR: The enone 3-(9-anthryl)-1-(2-pyridyl)-2-propenone undergoes a facile photochemical E to Z isomerisation as discussed by the authors.
TL;DR: In this paper, the chemical properties of ergosta-4, 6, 8(14), 22-tetraen-3-one (1) and 22-triene-3, 6-dione (4) were investigated.
Abstract: Chemical properties of ergosta-4, 6, 8(14), 22-tetraen-3-one (1) were investigated. Though 1 is rather stable to acids or bases, it reacts easily with two moleculres of oxygen on irradiation with UV light to give 6α, 9α-epidioxy-14α-hydroperoxyergosta-4, 7, 22-trien-3-one (2), which is transformed successively to 6α, 7α;8α, 9α-diepoxy-14α-hydroperoxyergosta-4, 22-dien-3-one (3) and 14α-hydroperoxy-9α-hydroxyergosta-4, 7, 22-triene-3, 6-dione (4) under these reaction conditions.
TL;DR: The propensity of abietenones such as 2 to form exclusively the extended enol(ate) into ring-B can be curbed by introducing an alkoxy group at C-7 in the abietane framework as discussed by the authors.
TL;DR: In this paper, 2-substituted N-ethyl succinimide and succinate diesters were obtained by adding a nitroalkane to the appropriate enedione derivative under basic conditions (DBU), with the concomitant elimination of nitrous acid, and selective reduction of the obtained enone with nickel boride, in methanol/THF.
Abstract: 2-Substituted N-ethyl succinimide and 2-substituted succinate diesters were obtained by two key steps: (i) Michael addition of a nitroalkane to the appropriate enedione derivative under basic conditions (DBU), with the concomitant elimination of nitrous acid, and (ii) selective reduction of the obtained enone with nickel boride, in methanol/THF. In this context the nirtoalkane acts as an alkyl anion synthon. By this method trimethyl tricarboxylates were also synthesized.