Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

One-step furan ring formation: Synthesis of furo[3,2-h]quinolones

The one-pot reaction of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate ( 6 ) with tert-butyl acetoacetate gave 3-tert-butyl 7-ethyl 9-cyclopropyl-4-fluoro-6,9-dihydro-2-methyl-6-oxofuro[3,2-h]quinoline-3,7-dicarboxylate ( 5 ). This regioselective cyclization was rationalized by the Hard and Soft Acids and Bases principle. By use of a similar furan-forming reaction, we prepared 2-(amino-methyl)furo[3,2-h]quinoline-7-carboxylic acid 4 . Compound 4 showed weak antibacterial activity.     

Synthesis of Hexa- and Octahydropyrido[3'2':4,5]thieno[3,2-d]pyrimidines

The reaction of N-methylmorpholinium 4-(2-chlorophenyl)-5-cyano-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolate with chloroacetamide in DMF in the presence of an excess of KOH gave 3-amino-2-carbamoyl-4-(2-chlorophenyl)-6-oxo-4,5,6,7-tetrahydrothieno[2,3-b]pyridine. Refluxing the latter with acyl chlorides in AcOH or heating in formic acid gave hexahydropyrido[3',2':4,5]thieno[3,2-d]pyrimidine derivatives and reaction with cyclohexanone gave a spiro-linked octahydropyrido[3',2':4,5]thieno[3,2-d]pyrimidine.     

Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

Acid-promoted furan annulation and aromatization: An access to benzo[b]furan derivatives

An unprecedented PTSA-promoted furan annulation and aromatization in one pot has been developed. This process offers a simple and efficient synthetic route for the construction of various highly substituted benzo[b]furan derivatives, which are widely used not only in drug active molecules but also organic semiconductor and organic light-emitting devices. The preliminary mechanism study indicated this transformation proceeded sequentially via furan annulation and aromatization.     

Facile synthesis of 3-substituted thieno[3,2-b]furan derivatives

A facile synthesis of dimethyl 3-hydroxythieno[3,2-b]furan-2,5-dicarboxylate is reported from the available methyl thioglycolate and dimethyl acetylenedicarboxylate starting materials. This compound represents an efficient precursor for the synthesis of 3-substituted thieno[3,2-b]furan derivatives.     

Planar beta-linked oligothiophenes based on thieno[3,2-b]thiophene and dithieno[3,2-b:2',3'-d]thiophene fused units

A series of planar beta-linked oligothiophenes based on thieno[3,2-b]thiophene and dithieno[3,2-b:2',3'-d]thiophene fused units were synthesized. The optical data indicate a blue shift of the absorption maximum in comparison to the alpha-linked analogues due to cross-conjugation between fused rings. The crystal structures of 3,3'-bi(thieno[3,2-b]thiophene) and 3,3';6',3"-ter(thieno-[3,2-b]thiophene) reveal edge-to-face pi-stacked dimer motifs, whereas the crystal structure of 3,3'-bis(dithieno[3,2-b:2',3'-d]thiophene) consists of face-to-face pi-stacked molecules. [structure: see text]     

An efficient method for the synthesis of thieno[3',2':2,3]pyrido-[4,5-d]-thiazolo[3,2-a]pyrimidinones

An efficient method for the preparation of thieno[3',2':2,3]pyrido[4,5-d]thiazolo[3,2-a] pyrimidin-5-ones 5 is described. The key intermediate, 7-(3-amino-4-cyano-5-phenyl aminothieno-2-yl)-5H-thiazolo-[80_TD$IF]3,2-a]pyrimidin-5-one(3), was synthesized from 7-chloromethyl-5H-thiazolo[3,2-a]pyrimidin-5-one(1)with potassium-(2,2-dicyano-1-phenylaminoethen-1-yl)thiolate(2) by Thorpe–Ziegler isomerization.Subsequent reaction of the intermediate amine with aromatic aldehydes via Pictet–Spengler reaction provided thieno-pyridine fused thiazolo[3,2-a]pyrimidines under p-Ts OH as catalyst in good yields.     

Palladium-catalyzed C-S coupling: access to thioethers, benzo[b]thiophenes, and thieno[3,2-b]thiophenes

The first C-S bond formation/cross-coupling/cyclization domino reaction using thiourea as a cheap and easy to handle dihydrosulfide surrogate has been developed. Structurally important biarylthioether, benzo[b]thiophenes, and thieno[3,2-b]thiophene scaffolds are provided in high yield.     

Anthra[1,2-b]furan and 1h-naphth[2, 3-g]indole derivatives

A number of previously inaccessible anthra[1,2-b]furan and 1H-naphth[2,3-g]indole derivatives were obtained by condensation of 1,4-anthraquinone with acetoacetic ester and its analogs. Quinones of the anthra[1,2-b]furan series were obtained by oxidation of the methoxy derivatives of anthra[1,2-b]furan.Translated from Khimiya Geterotsiklicheskikh Soedtaenii, No. 8, pp. 1027–1029, August, 1972.     

Heterocyclic quinones. XVI. Pharmacomodulation in the series of 11H-indolo[3,2-c]quinolinediones: synthesis, cytotoxicity and antitumor activity of 3-substituted 11H-pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones

With the aim of obtaining new antitumor drugs more active than previously described 11H-indolo[3,2-c]quinoline-1,4-diones and 7,8,9,10-tetrahydro-11H-indolo[3,2-c]quinoline-1,4-diones, the synthesis and activities of a series of 3-substituted 11H-pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones and of 7,8,9,10-tetrahydro-11H-pyrido-[3',4':4,5]pyrrolo[3,2-c] quinoline-1,4-diones were studied. Some quinones were more cytotoxic in vitro towards L1210 leukemia cells but were not active in vivo towards murine P388 leukemia.     

Synthesis of 1,2,4-triazolo[4,3-c]-, tetrazolo[1,5-c]-, and 1,2,4-triazino[5,6-c]pyrano[4'3':4,5]pyrrolo-[3,2-e]pyrimidine derivatives

4-Hydrazinopyrano[4',3':4,5]pyrrolo[2,3-d]pyrimidines served as precursors in the synthesis of new heterocyclic systems, namely, 1,2,4-triazolo[4,3-c]-, tetrazolo[1,5-c]-, and 1,2,4-triazino[5,6-c] pyrano[4',3':4,5]-pyrrolo[3,2-e]pyrimidines.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, 375014 Yerevan. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 700-703, May, 1995. Original article submitted January 10, 1995; revision submitted April 20, 1995.     

三组分一锅法合成3-甲基-1-苯基-4-芳基-4,11-二氢-4H-吡唑并[4',5':3,2]吡啶并[5,6-c]香豆素

以芳醛、4-羟基香豆素和3-甲基-1-苯基-5-氨基吡唑为原料,用少量冰醋酸作溶剂,三组分一锅法合成一系列吡唑并[4',5':3,2]吡啶并[5,6-c]香豆素衍生物,该反应产率高(79%～94%)、操作简单、后处理方便.产物的结构经红外光谱、核磁共振氢谱、元素分析及单晶X射线分析证实.