Showing papers on "Bicyclic molecule published in 1990"
TL;DR: PyBOP as discussed by the authors, an analog of BOP where dimethylamino groups are replaced with pyrrolidino, is the only analog exhibiting equivalent properties in peptide bond formation.
596 citations
459 citations
TL;DR: In this paper, the treatment of π-electron sufficient aromatic heterocycles such as title compounds with aryl bromides in the presence of tetrakis(triphenylphosphine)palladium gave the corresponding 2-aryl aromatic hetercycle.
Abstract: Treatment of π-electron sufficient aromatic heterocycles such as title compounds with aryl bromides in the presence of tetrakis(triphenylphosphine)palladium gave the corresponding 2-aryl aromatic heterocycles.
291 citations
285 citations
237 citations
TL;DR: In this article, a general strategy for the synthesis of highly substituted polycyclic aromatic and heteroaromatic compounds was developed, which is achieved simply by the irradiation of a dichloroethane solution of an acetylene derivative and a vinyl or aryl α-diazo ketone.
Abstract: A general strategy for the synthesis of highly substituted polycyclic aromatic and heteroaromatic compounds has been developed. The new aromatic annulation is achieved simply by the irradiation of a dichloroethane solution of an acetylene derivative and a vinyl or aryl α-diazo ketone. Mechanistically, the reaction proceeds via the photochemical Wolff rearrangement of the diazo ketone to generate an aryl- or vinylketene, followed by a cascade of three pericyclic reactions. A variety of substituted phenols, naphthalenes, benzofurans, benzothiophenes, indoles, and carbazoles can be prepared by using the method
166 citations
TL;DR: In this article, the 3,6-bis[trifluoromethyl] -et-[methoxycarbonyl]-1,2,4,5-tetrazines were reactivated with dienophiles.
158 citations
145 citations
TL;DR: In this paper, aldehydes, acides carboxyliques, and cetones are used for Oxydation d'alcools primaires et secondaires en aldehyde, acide-carboxylique, and Cetones.
Abstract: Oxydation d'alcools primaires et secondaires en aldehydes, acides carboxyliques, et cetones
138 citations
TL;DR: A number of compounds were orally effective at doses less than or equal to 1 mg/kg in blocking LTD4-induced "dyspnea" in guinea pigs and is currently under clinical investigation for asthma.
Abstract: 1,3,5-Substituted indoles and indazoles have been studied as receptor antagonists of the peptidoleukotrienes. The best of these compounds generally had a methyl group at the N1 position, a [(cyclopentyloxy)carbonyl]amino or 2-cyclopentylacetamido or N'-cyclopentylureido group at the C-5 position, and an arylsulfonyl amide group as part of the acidic chain at the C-3 position of the ring. Such compounds had in vitro dissociation constants (KB) in the range 10(-9) - 10(-11) M on guinea pig trachea against LTE4 as agonist and inhibition constants (Ki) less than or equal to 10(-9) M on guinea pig parenchymal membranes against [3H]LTD4. A number of compounds were orally effective at doses less than or equal to 1 mg/kg in blocking LTD4-induced "dyspnea" in guinea pigs. Compound 45 [N-[4-[[5-[[(cyclopentyloxy)carbonyl]-amino]-1-methylindol-3- yl]methyl]-3-methoxybenzoyl]-2-methylbenzenesulfonamide, ICI 204,219; pKB = 9.67 +/- 0.13, Ki = 0.3 +/- 0.03 nM, po ED50 = 0.3 mg/kg] is currently under clinical investigation for asthma. In the indole series, certain alkylsulfonyl amides possessing a 3-cyanobenzyl substituent at the N-1 position (60, 61) were produced that had KB less than or equal to 10(-9) M on guinea pig trachea.
132 citations
TL;DR: In this article, a substitution of type SN2 de l'anion enolate sur l'oxaziridine via un etat de transition is described, and a transition transition is defined.
Abstract: Le mecanisme met en jeu une substitution de type SN2 de l'anion enolate sur l'oxaziridine via un etat de transition «ouvert»
TL;DR: In this article, the X-ray structure of the metallacycle formed from titanacene methylene complex and 1-methylbicyclo[2.2.1.
Abstract: A variety of ester-substituted norbornenes react with titanamethylene complex (Tebbe's reagent) to yield stable
titanacyclobutanes. Endo esters do not react with the reagent in competition with the norbornene double bond.
The X-ray structure of the metallacycle formed from titanacene methylene complex and 1-methylbicyclo[2.2.l]hept-5-ene-2,3-dicarboxylic acid diisopropyl ester was determined. On heating, the metallacycle rearranged
to a carbene-olefin complex. The ratio of productive opening, cleavage of the bicycloheptane ring system, to
nonproductive opening, regeneration of the starting materials, is controlled by a variety of steric factors that
were studied and analyzed. The productive opening was detected by the formation of the product resulting from
the intramolecular trapping of the intermediate titanium alkylidene by the endo ester functionality in a Wittig-like
reaction to yield substituted bicyclo[3.2.0]heptenes. Rearrangement of the titanacycle formed from 4,4-dimethyltricyclo[
5.2.1.0^(1,5)]dec-8-ene-6-carboxylic acid tert-butyl ester yielded 10,10-dimethyl-3-methoxy-7-
vinyltricyclo[5.3.0.0^(2,5)]dec-2-ene, which was transformed into Δ ^(9(12))-capnellene in good yield.
TL;DR: The remaining compounds were less cytotoxic, with IC50's greater than 30 microM for 21, 23, 26, and 28, whereas no inhibition of L1210 cell growth was observed with compounds 17, 22, 24, 25, and 31 at 100 microM.
Abstract: The sodium salts of 4-chloro- and several 4-chloro-5-substituted-7H-pyrrolo[2,3-d]pyrimidines were treated with [1,3-bis(benzyloxy)-2-propoxy]methyl chloride (6) to provide the corresponding 4-chloro- and 4-chloro-5-substituted-7-[[1,3-bis(benzyloxy)-2-propoxy]methyl]pyrrolo [2,3-d]pyrimidines (7-11). Debenzylation with boron trichloride at -78 degrees C furnished 4-chloro- and several 4-chloro-5-substituted-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3- d]pyrimidines (12.16). Subsequent amination of 12-16 yielded the 4-amino-5-substituted-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3- d]pyrimidines (17-21). Treatment of 14 with methylamine and 13 and 14 with ethylamine yielded the 4-(alkylamino)-5-halo-7-[(1,3-dihydroxy-2- propoxy)methyl]pyrrolo[2,3-d]pyrimidines (22-24). Treatment of 12-15 with hydroxylamine in refluxing 2-propanol yielded the 5-substituted-4-(hydroxyamino)-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrol o [2,3-d]pyrimidines (25-28). Treatment of compound 12 with Pd/C under a hydrogen atmosphere has furnished the nebularine analogue 31. The antiproliferative activity of compounds 17-28 and 31 was studied using L1210 cells in vitro. The 4-amino- and 4-(hydroxyamino)-5-halogenated derivatives (compounds 18-20, 26-28) inhibited cell growth. Although the effect of compounds 18-20 and 27 on final growth rate was pronounced (IC50 = 2.3, 0.7, 2.8, and 3.7 microM, respectively), cells underwent at least one doubling before cell division stopped. The remaining compounds were less cytotoxic, with IC50's greater than 30 microM for 21, 23, 26, and 28, whereas no inhibition of L1210 cell growth was observed with compounds 17, 22, 24, 25, and 31 at 100 microM. The antiviral activity of these compounds also was tested. Compounds 18-20 and 26-28 were active against human cytomegalovirus and herpes simplex type 1. The 4-amino derivatives (18-20) were more active than the 4-hydroxyamino derivatives (26-28), the 4-amino-5-bromo and 4-amino-5-iodo derivatives produced more than five log reductions in virus titer at concentrations of 10-100 microM. Although some cytotoxicity was observed at these concentrations, compound 19 was active against murine cytomegalovirus in vivo. At 5.6 mg/kg, 14/15 animals survived compared to 10/15 treated with 5.6 mg/kg of ganciclovir or 1/15 treated with placebo.
TL;DR: Five compounds prepared by reacting arylamidines with sodium ethyl formylacetate or with ethyl propiolate to give pyrimidinones were found to have the best activity and were chosen for further pharmacological and toxicological study.
Abstract: With the use of the human basophil histamine release assay, 5-aryl-2-amino[1,2,4]triazolo[1,5-c]pyrimidines were found to be active as mediator release inhibitors. These compounds were prepared by reacting arylamidines with sodium ethyl formylacetate or with ethyl propiolate to give pyrimidinones. Treatment with phosphorus oxychloride gave a chloropyrimidine, which was converted to a hydrazinopyrimidine with hydrazine. Cyclization, using cyanogen bromide, gave the triazolo[1,5-c]pyrimidines, after a Dimroth rearrangement. Following a structure-activity evaluation, the 5-[3-(trifluoromethyl)phenyl]-2-amino (8-10), 5-(3-bromophenyl)-2-amino (8-13), 5-[3-(difluoromethoxy)-phenyl]-2-amino (8-11), and 5-(4-pyridinyl)-2-amino (6-7) compounds were found to have the best activity. They were chosen for further pharmacological and toxicological study.
TL;DR: In this paper, a new reaction involving bridging of macrodithionolactones to bicyclic systems is described, which follows the relative energy of the cis and trans products rather than the conformational preferences of the macrocycles.
Abstract: A new reaction involving bridging of macrodithionolactones to bicyclic systems is described. A series of macrodiolides was prepared and converted to the requisite macrodithionolactones. The latter substrates were induced to undergo bridging across the macrocyclic ring by exposure to sodium naphthalenide, leading to stable bicyclic systems upon addition of methyl iodide. The mixed thioketals so obtained were converted to a number of saturated or unsaturated bicyclic or polycyclic systems by removal of the sulfurs. The stereochemistry of bridging follows the relative energy of the cis and trans products rather than the conformational preferences of the macrocycles. This is confirmed by MM2 calculations and X-ray crystal structure determinations
TL;DR: The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j, which were prepared by the reaction of ketene dithioacetals with formamide or carbon disulfide, was described in this article.
TL;DR: Asymmetric, RmAlCln mediated Diels-Alder reactions of 1,3-dienes to N-enoyl derivatives were described in this paper.
TL;DR: In this paper, hydrogen fluoride-induced protiodetrimethylsilylation of trimethyl silylethynyl(phenyl)iodonium tetrafluoroborate (TFLB) was demonstrated to be a reagent for α-ethynylation of β-dicarbonyl compounds.
Abstract: Hydrogen fluoride-induced protiodetrimethylsilylation of trimethylsilylethynyl(phenyl)iodonium tetrafluoroborate (5), prepared from bis(trimethylsilyl)ethyne (4), affords ethynyl(phenyl)iodonium tetrafluoroborate (1), a reagent for α-ethynylation of β-dicarbonyl compounds under mild conditions.
TL;DR: Les reactions du titre appliquees a l'allyl-2 methyl-6 oxo-3 heptene-6 oate de methyle donne le methyl-5 methylene- 6 oxo -2 bicyclo [3.2.1] octanecarboxylate-1].
Abstract: Les reactions du titre appliquees a l'allyl-2 methyl-6 oxo-3 heptene-6 oate de methyle donne le methyl-5 methylene-6 oxo-2 bicyclo [3.2.1] octanecarboxylate-1 de methyle. Le [cyclohexene-1″ yl-3' oxo-1' propyl]-2 pentene-4 oate de methyle donne l'hexahydro methylene-9 oxo-2 ethano-1,4a naphtalene carboxylate-1 de methyle. Le dimethyl-2,6 oxo-3 undecadiene-6,10 oate de methyle donne le methyl-7a octahydro indenedione-1,5
TL;DR: An improved general synthesis of substituted homoprolines has been developed by using readily available substituted pyridines as mentioned in this paper, where the key step in this synthetic procedure involves the known conversion of pyridine N-oxides to 2-cyanopyridine in nearly quantitative yields
Abstract: An improved, general synthesis of substituted homoprolines has been developed by using readily available substituted pyridines. A key step in this synthetic procedure involves the known conversion of pyridine N-oxides to 2-cyanopyridines in nearly quantitative yields
TL;DR: In this article, a general protocol for the synthesis of α-amino-α- alkyl phosphonic acids in either enantiomeric form is described based on the alkylation of chiral bicyclic phosphonamides derived from ( R,R )- and ( S,S )-1,2-diaminocyclohexane.
TL;DR: Indole reacts with 1,2,4-triazines in the absence of solvent or in the presence of limited amounts of solvent to produce β- or γ-carbolines, benzo[f][1,7]naphthyridines, or the noncyclized 3-[5-(1, 2, 4-triazinyl)] indoles as mentioned in this paper.
Abstract: Indole reacts with 1,2,4-triazines in the absence of solvent or in the presence of limited amounts of solvent to produce β- or γ-carbolines, benzo[f][1,7]naphthyridines, or the noncyclized 3-[5-(1,2,4-triazinyl)] indoles. The combined yield of cycloadducts with tricarbalkoxytriazines exceeds 90%, with the production of γ-carbolines exceeding 80%. The regiochemistry of the adduct and the ratio of the products is determined mainly by electronic effects of the triazine substituents. Indole also undergoes a cyclocondensation reaction with tetramethyl 1,2-diazine-3,4,5,6-tetracarboxylate to give trimethyl 5H-6-oxophenanthridine-2,3,4-tricarcarboxylate
TL;DR: In this article, the Ni(0)-trialkylphosphine complex-catalyzed cycloaddition of terminally silyl-substituted diynes with CO 2 was investigated.
Abstract: Here we investigated synthesis of silyl-substituted bicyclic α-pyrones by the Ni(0)-trialkylphosphine complex-catalyzed cycloaddition of terminally silyl-substituted diynes with CO 2