Substituted Pyrrolo[3,4-<Emphasis Type="Italic">a</Emphasis>]carbazoles from Reactions between 3-(1-Methoxy-vinyl)indoles and Maleimides

Summary. 5-Methylenolether derivatives of pyrrolo[3,4-a]carbazoles were obtained from cycloadditions between 3-(1-methoxyvinyl)-1-tosylindole and N-substituted maleimides. They were transformed into the hydroxy derivatives by treatment with H₂SO₄, selectively reduced to the ether by H₂/Pd–C, and in the imide moiety by L-Selectride^?. From the analogous BOC protected indole derivative the parent α,β-unsaturated ketones were obtained, which were transformed into hydroxyimino compounds, and which could be deprotected by heating to the melting point. Deprotection of the tosyl derivatives was not successful. The imide part of the molecule was hydrolyzed using methanolic NaOH. The stereochemistry of all products was elucidated mainly by spectroscopic methods, and compared with results of calculations.     

Synthesis of Substituted Pyrrolo[3,4‐a]carbazoles

The cycloaddition between N‐protected 3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indoles and substituted maleimides (= 1H‐pyrrole‐2,5‐diones) yielded substituted pyrrolo[3,4‐a]carbazole derivatives bearing an additional succinimide (= pyrrolidine‐2,5‐dione) moiety either at C(5a) or C(10b) depending on the type of the protection group at the indole N‐atom. Derivatives substituted at C(10b) were isolated when the protection group, Me₃Si or Boc (^tBuOCO), was eliminated during the reaction (Schemes 2 and 3), whereas a substitution at C(5a) was observed when an electron‐withdrawing group, Tos (4‐MeC₆H₄SO₂) or pivaloyl (Me₃CCO), was not eliminated (Scheme 1). Complex results were found in reactions between 1‐(trimethylsilyl)‐3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indole, in contrast to formerly reported results (Scheme 3). Some derivatives of 1H,5H‐[1,2,4]triazolo[1′,2 : 1,2]pyridazino[3,4‐b]indole‐1,3(2H)‐dione were obtained from reactions with 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (Scheme 2). All structures were established by spectroscopic data, by calculations, and one representative structure was confirmed by an X‐ray crystallographic analysis (Fig.). Finally, the formation of the different structure types was discussed, and compared with similar reactions reported in the literature.     

New Pyrrolo[1,2-a]azepine Type Alkaloids from Stemona and Stichoneuron (Stemonaceae)

Summary. Three new pyrroloazepine type alkaloids, stichoneurines A and B and 6-hydroxycroomine were isolated from the lipophilic root extracts of Stichoneuron caudatum and Stemona tuberosa collected in Thailand together with the already known croomine, tuberostemonine, and tuberostemonine A. The structures were elucidated by spectroscopic methods including H/H-COSY, HMQC, and HMBC. Information on the relative stereochemistries and conformational behaviour was obtained by analysis of the NOESY spectra. The formation of pyrroloazepine alkaloids in the genus Stichoneuron is reported for the first time and supports its affiliation to the family Stemonaceae. The occurrence of two different types of alkaloids, of the tuberostemonine and croomine series, in different geographical provenances of Stemona tuberosa is of special chemosystematic interest and may contribute to a more natural species delimitation within that complex group.     

New Pyrrolo[1,2-a]azepine Type Alkaloids from Stemona and Stichoneuron (Stemonaceae)

Three new pyrroloazepine type alkaloids, stichoneurines A and B and 6-hydroxycroomine were isolated from the lipophilic root extracts of Stichoneuron caudatum and Stemona tuberosa collected in Thailand together with the already known croomine, tuberostemonine, and tuberostemonine A. The structures were elucidated by spectroscopic methods including H/H-COSY, HMQC, and HMBC. Information on the relative stereochemistries and conformational behaviour was obtained by analysis of the NOESY spectra. The formation of pyrroloazepine alkaloids in the genus Stichoneuron is reported for the first time and supports its affiliation to the family Stemonaceae. The occurrence of two different types of alkaloids, of the tuberostemonine and croomine series, in different geographical provenances of Stemona tuberosa is of special chemosystematic interest and may contribute to a more natural species delimitation within that complex group.     

Cyclization of Nitrospirobenzopyrans to Bridged Benzoxazepino[3,2-a]indoles

Condensation of 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with 5-nitrosalicylaldehyde afforded 1′-[(N-monosubstituted carbamoyl)methyl]indoline nitrospirobenzopyrans. Treatment of the latter with strong base led to the formation of a mixture of cis/trans-5a,13-methano-1,3-benzoxazepino[3,2-a]indoles. Results of semiempirical calculations gave evidence that such a transformation of nitrospirobenzopyrans to bicyclic indole derivatives could proceed via a single transition state, where the negatively charged carbon atom attacks the vinylic double bond of the spiropyran system.     

Regioselective 1,3-Dipolar Cycloaddition Reactions of Unsymmetrical Münchnones (1,3-Oxazolium-5-olates) with 2- and 3-Nitroindoles. A New Synthesis of Pyrrolo[3,4-b]indoles

The unsymmetrical mesoionic münchnones 13 (3-benzyl-2-methyl-4-phenyl-1,3-oxazolium-5-olate) and 14 (3-benzyl-4-methyl-2-phenyl-1,3-oxazolium-5-olate) react with the N-protected 2- and 3-nitroindoles 1 (ethyl 2-nitroindole-1-carboxylate), 6 (3-nitro-1-(phenylsulfonyl)indole), and 17 (ethyl 3-nitroindole-1-carboxylate) in refluxing THF to afford in good to excellent yields the pyrrolo[3,4-b]indoles 15 (2-benzyl-1-methyl-3-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 16 (2-benzyl-3-methyl-1-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 18 (2-benzyl-1-methyl-3-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole), and 19 (2-benzyl-3-methyl-1-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole). In several cases the regiochemistry, which is opposite to that predicted by FMO theory, is very high and leads essentially to a single pyrrolo[3,4-b]indole; e.g., 6+13→19 in 74% yield.     

new simple and one-pot synthetic routes to polyfunctionally substituted imidazo-[1,2-a]pyridines, pyrido[1,2-a]pyrimidines, pyrido-[1,2-a]-1,3-diazepines, and imidazo[1,2-a]pyrimidines

Reactions of arylidenemalononitriles with 2-nitromethylene-substituted imidazolidine, hexahydropyrimidine, and hexahydro-1,3-diazepine afforded the title derivatives. Reaction of 2-nitromethylenehexahydropyrimidine with benzylamine or n-butylamine and formalin in a molar ratio of 1:1:2 gave the hexahydro-1H-imidazo[1,2-c]pyrimidine derivatives. Treatment of 2-nitromethyleneimidazolidine and hexahydropyrimidine with secondary aliphatic amines and formalin in a molar ratio of 1:1:1 afforded the corresponding methylene bis-compounds. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1850–1853, December, 2005.     

Efficient Syntheses of Substituted Carbazoles and Cyclopent[b]indoles from 1-Methyl-3-(benzotriazol-1-ylmethyl)indole

1-Methyl-3-(benzotriazol-1-ylmethyl)indole (1) undergoes lithiation and 1,4-addition with a variety of alpha,beta-unsaturated ketones and aldehydes. Subsequent treatment with an acidic resin in refluxing 1,4-dioxane causes intramolecular cyclization followed by aromatization to furnish a wide range of 1,3-di-, 2,3-di-, and 1,2,3-trisubstituted carbazoles 6a-j and 8 in moderate to excellent yields. NMR study is described to discriminate between structures of types 6 and 8 on the basis of (1)H-(13)C long-range correlation. Treatment of 1 with styrenes in the presence of zinc bromide results in formal [3 + 2] cycloaddition to give cyclopent[b]indoles 14a-c in good yields. When 1 is first lithiated and reacts with electrophiles, the resulting alkylation products undergo similar [3 + 2] additions with styrenes to give 1-functionalized cyclopent[b]indoles 15 and 16with a high degree of stereoselectivity.     

微波辐射促进的3-烷基取代咪唑并[1,5-a]吡啶合成

分别在常规加热和微波辐射条件下, 由双(2-吡啶甲酰)、二(2-吡啶)甲酮与脂肪醛及醋酸铵在醋酸溶剂中反应成功地制备了3-烷基取代的咪唑并[1,5-a]吡啶. 实验结果表明: 微波法比传统的合成方法产率高、反应时间短. 产物的结构经过¹H NMR, MS和元素分析表征.     

2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indoles. II. Reversible transformation of 1-alkyl-2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)cyclohexanol into 1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles

Treatment of 2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)-1-methylcyclohexanol ( 2a ) with acetic anhydride or methyl isocyanate gave 2-acetyl-2,3,4,9-tetrahydro-1-(6-oxoheptylidene)-1H-pyrido[3,4-b]indole ( 3 ) or 1,3,4,9-tetrahydro-N-methyl-1-(6-oxoheptylidene)-2H-pyrido[3,4-b]indole-2-carboxamide ( 4 ), respectively. Simpler analogues, 1-alkyl-4,9-dihydro-3H-pyrido[3,4-b]indoles, 7 , subjected to identical reaction conditions, gave 2-acetyl-1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles 8 and 1,3,4,9-tetrahydro-N-methyl-1-alkyli-dene-2H-pyrido[3,4-b]indole-2-carboxamides 9 , respectively. A limited lanthanide shift reagent study to determine stereochemical assignments was also performed.     

Reactions of N - and C -alkenylanilines: VIII. Synthesis of functionalized cycloalka[ b ]indoles from o -(cycloalk-2-en-1-yl)anilines

N-Acyl-2-(cyclohex-2-en-1-yl)anilines react with molecular iodine to give the corresponding N-acyl-1-iodo-1,2,3,4,4a,9a-hexahydrocarbazoles which undergo isomerization into 1-R-2a,3,4,5,5a,10a-hexahydro[1,3]oxazolo[5,4,3-j,k]carbazol-10-ium iodides; no isomerization occurs with N-acetyl-3-iodo1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole. The reaction of N-p-tolylsulfonyl-3,4,4a,9a-tetrahydrocarbazoles with hydrogen peroxide leads to the formation of a single 1,2-epoxy derivative with trans orientation of the nitrogen-and oxygen-containing rings. N-p-Tolylsulfonyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles give rise to the corresponding 2,3-epoxy derivatives with both trans and cis orientation of the dihydropyrrole and oxirane fragments. The resulting epoxides undergo trans-opening with formation of N-p-tolylsulfonyl-1-hydroxy-2-methoxy-1,2,3,4,4a,9a-hexahydrocarbazoles and N-p-tolylsulfonyl-3-hydroxy-2-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles on heating in methanol in the presence of KU-2 cation exchanger. Mutual orientation of the oxirane and nitrogen-containing rings in the epoxides derived from cyclopenta[b]-indoles was proved by X-ray analysis. Original Russian Text ? R.R. Gataullin, N.A. Likhacheva, K.Yu. Suponitskii, I.B. Abdrakhmanov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 9, pp. 1316–1326. For communication VII, see [1].     

Reactions of 3-[3-Chlorophenyl]-1-[4-(3,4-Methylenedioxybenzylidine) a Minophenyl]Prop-2-Enone with Some Nucleophiles

The action of 2-mercaptoacetic acid, thiosemicarbazide and hydrazine hydrate on the titled compound 1 is studied. On the other hand, the behaviour of the titled compound towards thiourea, ethyl acetoacetate and malononitrile under Michael's conditions is reported. The structure of the new heterocycles 2 - 8 is discussed in the light of IR and ¹HNMR spectra.     

Synthesis of 1-substituted-2,3,4,9-tetrahydro-(2-oxopropyl)-1H-pyrido [3,4-b] indoles and their base-catalyzed rearrangements to N- [2-[2-(1-alkyl-3-oxobutenyl)-1H-indol-3-yl] ethyl]acetamides

The condensation of 1H-indole-3-ethanamides, 1 , with 2,4-pentanediones, 2 , gave enamines 3 . Acid catalyzed ring closure of 3 gave 1-(1-substituted-2,3,4,9-tetrahydro- (2-oxopropyl) -1H-pyrido [3,4-b] indoles 4 . Subsequent N-acetylation yielded 5 which sequentially produced 2,3-disubstituted indoles 6 and 7 resulting from C? N bond cleavage after treatment with sodium alkoxide in ethanol. Controlled catalytic hydrogenation of the latter gave saturated derivatives 8 and 9 .     

Dihydropyrrolo[3,4-b]- and dihydropyrimido[4,5-b]indoles

Aromatic aldehydes react with indole-2-carboxylic acid azides under acid catalysis conditions to give the corresponding 3-(-halobenzyl)indoles, which react with aliphatic and aromatic amines to give the corresponding aminobenzylindoles. The latter undergo intramolecular cyclization to dihydropyrrolo[3,4-b]indoles at room temperature and are converted to dihydropyrimido[4,5-b]indoles through the Curtius rearrangement when they are heated to 80-110°C. Acetylation of the latter products gives N- and O-acetyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 935–939, July, 1982.     

Synthesis of imidazo[4,5-a]acridones and imidazo[4,5-a]acridines as potential antibacterial agents

Abstract  

New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug.     

新型环烷烯并嘧啶并噻唑-3-酮类化合物的合成

以环戊酮、环庚酮为起始原料合成的环烷烯并[1,2-d]嘧啶-2-硫酮(2)与氯乙酸、芳香醛反应, 合成具有潜在抗癌活性的稠合杂环化合物5-芳基-2,8-二芳亚甲基-2,3,6,7-四氢-5H,8H-环戊烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(3)以及5-芳基-2,10-二芳亚甲基-2,3,6,7,8,9-六氢-5H,10H-环庚烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(4). 3和4的结构经¹H NMR, IR, MS分析确认.     

6-取代苄硫基-3-(3,4,5-三甲氧基苯基)-1,2,4-三唑[3,4-b][1,3,4]噻二唑类化合物的合成与抑菌活性

以4-氨基-5-(3,4,5-三甲氧基苯基)-3-巯基-1,2,4-三唑为原料,环化得到6-巯基-3-(3,4,5-三甲氧基苯基)-1,2,4-三唑[3,4-b][1,3,4]噻二唑再与取代苄氯反应,得到9个6-取代苄硫基-3-(3,4,5-三甲氧基苯基)-1,2,4-三唑[3,4-b][1,3,4]噻二唑类衍生物3a～3i.其结构经IR,1H NMR,MS和元素分析确证.初步生物活性测试结果表明部分化合物有一定的杀菌活性.     

Diels-alder reactions of 3-(2-nitrovinyl)indoles: Formation of carbazoles and bridged carbazoles

The Diels-Alder reactions of 1-substituted-3-(2-nitrovinyl)indoles 3 with quinones and acetylenes give aromatized 1:1 adducts (- nitrous acid) ( 1 ) or (- nitrous acid, -2 hydrogens) 2,5 . Likewise, dimerization (-2 nitrous acids) of 3 gives aromatized 2-(3-indolyl)carbazoles 4 . In contrast, 3 reacts with maleimides 6 to give 1:2 adducts (- nitrous acid or -2 hydrogens) 10 and 11 , respectively, along with smaller amounts of 1:1 adducts (- nitrous acid, -2 hydrogens; or -4 hydrogens) 12 and 13 , respectively. A mechanism for formation of the nitro products 11 and 13 is discussed. A 1:2 adduct (-2 hydrogens) 19 was also obtained from a Diels-Alder reaction between maleimide and the vinylindole produced in situ by condensing 1-methylindole with acetone. The stereochemisty of this 1:2 adduct has been determined by X-ray crystallography.