Studies on cyclic dipeptides, II. Methylated modifications ofcyclo-[Phe-His]

Summary Synthesis of seven new cyclic dipeptides and their conformational analysis based on¹HNMR spectra is reported as well as their application as models to elucidate the mechanism of cyclic dipeptide catalysis in enantioselective mandelonitrile formation. Further evidence is presented to support the view that a highly ordered supramolecular complex of dipeptides acts as catalyst.

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Untersuchungen an cyclischen Dipeptiden, 2. Mitt.: Methylierte Derivate von cyclo-[Phe-His]

Zusammenfassung Es wird die Synthese sieben neuer cyclischer Dipeptide, ihre Konformationsanalyse (basierend auf¹H-NMR-Daten) und ihre Anwendung als Modelle zur Aufklärung des Mechanismus der dipeptidkatalysierten enantioselektiven Mandelsäurenitrilsynthese beschrieben. Weitere Hinweise zur Stützung der Annahme, daß ein hoch geordneter supramolekularer Komplex aus Dipeptiden für die Katalyse ausschlaggebend ist, werden vorgelegt.

     

Studies on mechanisms of the rearrangement of thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines into thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines

Recyclization of thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines was studied experimentally and theoretically by B3LYP/6-31G** calculations in the gas phase and in solution (EtOH). The experimentally observed characteristic features of the isomerization (the possibility of the Dimroth rearrangement occurring by the ANRORC mechanism and high energy barriers in acid-catalyzed reactions) were confirmed by quantum chemical calculations. Substituents in the triazole ring were found to play the principal role in the rearrangement. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2164–2171, December, 2006.     

N,C10-Überbrückte Morphinalkaloide, 5H-10,13-Iminoethano-phenanthro[4,5-bcd]furan, 3. Mitt.

Summary In continuation of our recent papers [2, 3] a successful approach to N,C-10-bridged morphine derivatives by rearrangement of the chloroacetate of the previously described indolinocodeinone dimethylacetal is described.

     

Deoxypegan-1-one derivatives. synthesis and borohydride reduction of 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones

3-[(E)-Arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones were prepared by reaction of quinazolyl-2-propionic acid hydrochloride with aromatic aldehydes in acetic anhydride in the presence of Et₃N. 3-[(E)-Arylmethylidene]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-ols were formed by reduction of the 3-arylidene derivatives with sodium borohydride in methanol, readily lost water when heated with acids, and were converted into 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolines. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 463–467, September–October, 2006.     

Condensed Pyridine Bases. Synthesis and Reactions of Benzofuro[2,3-c]indeno[2,1-e]-, Benzothieno[2,3-c]Indeno[2,1-e]-, Benzofuro-[3,2-c]Indeno[2,1-e]- and Thieno[2,3:4′,5′]-thieno[3,2-c]indeno[2,1-e]pyridines

Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5-ethylthieno[2,3-b]thiophene. Starting from hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic anhydride in the presence of 70% HClO₄ leads to the formation of pentacyclic pyrilium salts. Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction using NaBH₄ has been studied.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 435–443, March, 2005.     

Synthesis of 8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine

8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine has been synthesized by the interaction of 6-tert-butyl-3-hydrazino-1,2,4-triazolo[3,4-c]-1,2,4-triazin-5-one with formic acid. The conditions of carrying out the reaction are discussed. Spectral characteristics are given.     

Synthesis and properties of 1,2,4-triazolo[4,3-d]-1,2,4-triazolo-[3,4-f]furazano[3,4-b]pyrazines

New methods for the synthesis of 1,2,4-triazolo[4,3-d]-1,2,4-triazolo[3,4-f]furazano[3,4-b]pyrazines with functional substituents of various types are proposed and some properties of these compounds are studied. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1776–1778, October, 1993.     

Reactions of cyclic 1,3-dicarbonyl compounds with 1,2(1,4)-dihydro-1-methyl-2(4)-methylene-N-heterocycles. A new access to 6,12-methano-dibenz[d,g]-[1,3]oxazocinones

Summary The enamine-type methylene-N-heterocycles1–5 react with cyclic 2-ethoxymethylene-1,3-dicarbonyl compounds6 to give 2-[2-(hetarylidene)ethylidene]-1,3-dicarbonyl compounds7–14. The result of the reactions between 1,2-dihydro-1-methyl-2-methylene-quinoline (1a) and cyclic 1,3-dicarbonyl compounds depends on the nature of the dihydro intermediatesA/B. Dehydrogenation of keton intermediatesA results in 2-(1,2-dimethyl-4(1H)-quinolylidene)-1,3-dicarbonyl compounds17–21. Enol intermediatesB with 6-membered dicarbonyl ring form 6,12-methano-dibenz-[d,g][1,3]oxazocinones22–25.¹H NMR spectra and X-ray structure analysis prove the structure of23.

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Reaktionen cyclischer 1,3-Dicarbonylverbindungen mit 1,2(1,4)-Dihydro-1-methyl-2(4)-methylen-N-heterocyclen. Ein neuer Zugang zu 6,12-Methano- dibenz[d,g][1,3]oxazocinonen

Zusammenfassung Aufgrund ihres Enamincharakters reagieren die Methylen-N-heterocyclen1–5 mit cyclischen 2-Ethoxymethylen-1,3-dicarbonylverbindungen6 zu den 2-[2-(Hetaryliden)ethyliden]-1,3-dicarbonylverbindungen7–14. Das Ergebnis der Reaktionen zwischen 1,2-Dihydro-1-methyl-2-methylen-chinolin (1a) und cyclischen 1,3-Dicarbonylverbindungen hängt von der Natur der zwischenzeitlich entstehenden DihydroverbindungenA/B ab. Die Intermediat-KetoneA gehen durch Dehydrierung während der Reaktion in die 2-(1,2-Dimethyl-4(1H)chinolyliden)-1,3-dicarbonylverbindungen17–21 über. Die Intermediat-EnoleB mit sechsgliedrigem Dicarbonylring bilden in intramolekularer Reaktion die 6,12-Methano-dibenz[d,g][1,3]oxazocinone22–25, deren Struktur am Beispiel der Verbindung23 durch¹H-NMR sowie durch Röntgenkristallstrukturanalyse bewiesen wird.

     

Purines,pyrimidines, and related fused systems. 19. Use of S N H methodology for the synthesis of a new heterocyclic system,pyrrolo[3",2":3,4]pyrimido[4,5-c]pyridazine

Sonogashira cross-coupling of 3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione with terminal alkynes afforded the corresponding 3-(alkyn-1-yl) derivatives. Oxidative amination of the latter compounds with primary alkylamines was accompanied by heterocyclization to give 6,8-dimethylpyrrolo[3",2":3,4]pyrimido[4,5-c]pyridazine-7,9(6H,8H)-diones.     

Synthesis and Properties of Substituted Isoxazolo[3',4':4,5]thieno[2,3-b]pyridines

We synthesized derivatives of a novel heterocyclic system, isoxazolo[3',4':4,5]thieno[2,3-b]pyridine by sequential conversions in three steps: isomerization of 2-(2-R-ethylthio-2-oxo)-3-pyridyl cyanides obtained by alkylation from substituted 3-cyano-2(1H)-pyridinethiones by -halomethyl ketones in alkaline medium, to form 3-aminothieno[2,3-b]pyridines; diazotization of the amino group followed by nucleophilic substitution of the diazonium group by an azido group, bypassing the step of isolating the diazonium salts; and thermolysis of the azides formed.     

[3,4]-annulated pyrroles 1. Polynuclear heterocyclic systems based on pyrrolo[3,4-d]pyrimidine-2,4-dione

The intramolecular electrophilic substitution in 6-functionalized 1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-diones was used for the synthesis of pyrimido[4′,5′:3,4]-pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione, pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,2,4]benzo-triazine-8,10(7H,9H)-dione, and 2H-pyrimido[4′,5′:3,4]pyrrolo[1,2-a]indole-2,4,11(1H, 3H)-trione derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2180–2185, December, 2006.     

Reaction of 6-methoxybenzo[b]furan-3(2H)-one and benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes as a convenient synthetic route to substituted 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans and 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans

The reactions of 6-methoxybenzo[b]furan-3(2H)-one with 2-aryl-1,1-dicyanoethylenes and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans. The reactions of benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes or with aromatic aldehyde and one mole of malononitrile produce 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans.     

Novel heterocyclic systems based on 8-R-4,5-dihydro-4,4-dimethyl-[1,2]dithiolo[3,4-c]quinoline-1-thiones

Based on the reaction of 8-R-4,5-dihydro-4,4-dimethyl[1,2]dithiolo[3,4-c]quinoline-1-thiones with oxalyl chloride followed by the reactions of 1,3-dipolar cycloaddition and diene synthesis with participation of acetylenedicarboxylic acid dimethyl ester, we have developed approaches to synthesis of novel polycondensed heterocyclic systems: [1,2]dithiolo[3,4-c]pyrrolo[3,2,1-ij]quinoline-4,5-dione, 6-(1,3-dithiol-2-ylidene)-1,2-dioxo-5-thioxo-7H-pyrrolo[3,2,1-ij]quinoline and 4,5-dioxospiro(pyrrolo)-[3,2,1-ij]thiopyrano[2,3-c]quinoline-11,2′-[1,3]dithiole. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 610–615, April, 2006.     

Condensed thiazoles,I: Synthesis of 5,7-disubstituted thiazolo[4,5-d]pyrimidines as possible anti-HIV,anticancer, and antimicrobial agents

Summary A convenient and simple synthesis of 5-mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo-[4,5-d]pyrimidin-7(6H-one(2) and its 5,7-dichloro (3), 5,7-diazido (4), 5,7-diamino (5), 5,7-dimerapto (6), 5,7-dimethylthio (7), and 6-methyl-5-methylthio (8) derivatives is described. The prepared compounds were screened for theirin vitro anti-HIV, anticancer, antibacterial and antifungal activities.

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Kondensierte Thiazole, 1. Mitt.: Synthese von 5,7-disubstituierten Thiazolo[4,5-d]pyrimidinen als potentielle anti-HIV, anticancerogene und antimikrobielle Verbindungen

Zusammenfassung Die Synthese von 5-Mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo[4,5-d-pyrimidin-7(6H)-on (2) und seiner 5,7-dichloro-(3), 5,7-diazido-(4), 5,7-dimanio-(5), 5,7-dimercapto-(6), 5,7-dimethylthio- (7) und 6-methyl-5-methylthio-Derivaten (8) wird beschrieben. Die hergestellten Verbindungen wurden auf ihrein vitro anti-HIV, anticancerogenen, antibakteriellen und antimykotischen Aktivitäten geprüft.

     

Formylation of Furyl-substituted Imidazo[1,2-a]pyridine, Imidazo[1,2-a]pyrimidine and Imidazo[2,1-b]thiazole

Vilsmeier formylation of 2-(2-furyl)-substituted imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine, and also 6-(2-furyl)imidazo[2,1-b]thiazole with 1 mole of reagent occurs at the free position of the imidazole ring, while with an excess of the reagent it also occurs at the position 5 of the furyl group.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.