Synthesis of substituted indolizino[8,7-<Emphasis Type="Italic">b</Emphasis>]indoles from harmine and their biological activity

The reaction of harmine with phenacyl bromides or ethyl bromoacetate gives quaternized harmine derivatives. The cyclization of the phenacylharminium salts yields the corresponding 2-aryl-11H-indolizino[8,7-b]indoles. Vilsmaier-Haack formylation of 11H-indolizino[8,7-b]indoles leads to the corresponding 3,10-bisformyl derivatives. The acylation proceeds selectively at C(3) to give 3-acetyl-2-aryl-11H-indolizino[8,7-b]indole.     

Synthesis of purinobenzothiazine and pyridothiazinopurine derivatives. Two new heterocyclic ring systems

The synthesis of derivatives of two new heterocyclic systems, purino[8,7-b][1,3]benzothiazine and pyrido[3′,2′:5,6][1,3]thiazino[3,2-f]purine, was effected by the Ullmann reaction between 8-mercaptotheophylline or 8-bromotheophylline with the appriopriately substituted benzoic or nicotinic acid, respectively. The 8,8′-dithiobistheophylline is also reported.     

Solid-phase synthesis of a type II′ β-turn peptido-mimetic library

The solid-phase synthesis of a dipeptide derived 2-amino-3-oxohexahydroindolizino[8,7-b]indole-5-carboxylate system (IBTM) is described. The IBTM moiety is formed via a solid-phase mediated Pictet-Spengler reaction of N-terminal tryptophan and the 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl (Dmab) ester of Fmoc protected aspartic acid β-aldehyde followed by γ-lactamization. This synthesis allows the regio- and stereoselective incorporation of a dipeptide surrogate of type II′ β-turns. The procedure is easily adaptable to combinatorial synthesis and a 576-member library was synthesized.     

Synthesis of condensed tricyclic pyrazolo[3,4-b]thieno[2,3-d]pyridine and related isostere derivatives

In this paper we report the synthesis of an isosteric series of new heterotricyclic derivatives, corresponding to pyrazolo[3,4-b]thieno[2,3-d]pyridine ( 1 ), pyrazolo[3,4-b]furano[2,3-d]pyridine ( 2 ) and pyrazolo[3,4-b]pyrrolo[2,3-d]pyridine ( 3 ). These functionalized compounds were obtained, in high overall yield, by an ‘one-pot’ reaction of the chloroester intermediate 4 , possessing the pyrazolo[3,4-b]pyridine system, with an adequate α-hetero-acetyl ester derivative, in SNAr/Dieckman cyclization type consecutive reactions.     

Synthesis of 2,9-dialkylated phenanthro[1,2-b:8,7-b′]dithiophenes via cross-coupling reactions and sequential Lewis acid-catalyzed regioselective cycloaromatization of epoxide

Phenanthro[1,2-b:8,7-b′]dithiophene (PDT) was prepared via Suzuki–Miyaura or Negishi cross-coupling of a 2-thienylboron or -zinc compound with 1,4-dibromobenzene, followed by Lewis acid-catalyzed regioselective cycloaromatization of the epoxide. A series of 2,9-dialkylated phenanthro[1,2-b:8,7-b′]dithiophene (PDT) derivatives could also be synthesized in good yields by Suzuki–Miyaura coupling of the brominated PDT with alkylboranes by introducing linear alkyl substituents.     

Synthesis of New Fused Pirano[4,3-b]pyridine Derivatives

A method was developed for the synthesis of pyrano[4,3-b]thieno[3,2-e]pyridine derivatives based on the reaction of 3-amino-7-ethyl-7-methyl-7,8-dihydro-5H-pyrano[4,3-b]thieno[3,2-e]pyridine-2-carboxylic acid ethyl ester with chloroacetic acid chloride, triethyl orthoformate, hydrazine hydrate, and also phenyl chloroformate. The synthesis of various new representatives of pyrano[2″,3″:5′,6′]pyrido[3′,2′:4,5]thieno[3,2-dl-pyrimidine series was carried out.

     

Synthesis of fused purinoquinazolines. Three new heterocyclic ring systems

The Ullmann reaction of 8-aminotheophylline or 8-aminocaffeine with 2-chlorobenzoic acid and of 8-bromotheophylline with ethyl-2-aminobenzoate afforded derivatives of three new heterocyclic systems: purino[7,8-α]quinazoline-5,9,11(6H,8H,10H)-trione, purino[8,9-b]quinazoline-2,4,11(1H,3H,5H)-trione and purino[8,7-b]quinazoline-2,4,6(1H,3H,11H)-trione, respectively.     

Furopyridines. III. A new synthesis of furo[3,2-b]pyridine

A convenient synthesis of furo[3,2-b]pyridine and its 2- and 3-methyl derivatives from ethyl 3-hydroxypiconate ( 1 ) is described. The hydroxy ester 1 was O-alkylated with ethyl bromoacetate or ethyl 2-bromopropionate to give the diester 2a or 2b . Cyclization of compound 2a afforded ethyl 3-hydroxyfuro[3,2-b]pyridine-2-carboxylate ( 3 ) which in turn was hydrolyzed and decarboxylated to give furo[3,2-b]pyridin-3-(2H)-one ( 4a ). Cyclization of 2b gave the 2-methyl derivative 4b . Reduction of 4a and 4b with sodium borohydride yielded the corresponding hydroxy derivative 5a and 5b respectively, which were dehydrated with phosphoric acid to give furo[3,2-b]pyridine ( 6a ) and its 2-methyl derivative ( 6b ). 2-Acetylpyridin-3-ol ( 8 ) was converted to the ethoxycarbonylmethyl ether ( 9 ) by O-alkylation with ethyl bromoacetate, which was cyclized to give 3-methylfuro[3,2-b]pyridine-2-carboxylic acid ( 10 ). Decarboxylation of 10 afforded 3-methylfuro[3,2-b]pyridine ( 11 ).     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1- b ]quinazolin-9-one Derivatives

 A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives.     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1-b]quinazolin-9-one Derivatives

Summary.  A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives. Received March 22, 2001. Accepted (revised) May 11, 2001     

Photochemical synthesis of heteroatom-containing polycyclic aromatic compounds

Anthra[2,1-b]furan, anthra[2,1-b]benzo[d]furan, anthra[2,1-b]thiophene, anthra[1,2-b]thiophene, anthra[2,1-b]benzo[d]thiophene, anthra[2,1-b]pyrrole and naphtho[2,3-c]carbazole derivatives were synthesized in fairly good yields by a one-pot photocycloaddition reaction of 2,3-disubstituted 1,4-naphthoquinone with 1,1-diarylethylene. This is the first reported synthesis of these aromatic compounds.     

Synthesis of condensed quinoxalines. Part II

A novel efficient synthesis of fluorescent, fused quinoxalines was achieved. 7-Triazolyl-1,4-dioxino[2,3-b]-quinoxalines were synthesized by the diazotisation of 7-amino-1,4-dioxino[2,3-b]quinoxaline and coupling with selected aromatic amines followed by air oxidation. Diazotised aryl amines were coupled with 7-amino-1,4-dioxino[2,3-b]quinoxalines followed by subsequent air oxidation afforded 1,4-dioxino[2,3-b]quinoxalino-[6,5-d]1,2,3-triazoles. 7-Amino-1,4-dioxino[2,3-b]quinoxaline was condensed with conjugated enol ethers followed by cyclization in dowtherm resulted in 1,4-dioxino[2,3-b]quinoxalino[6,5-b]pyridines.     

Novel pyrano[3,2-b]indole derivatives: synthesis and some properties

Acid treatment of β-(3-acetoxyindol-2-yl)-α-cyanoacrylic acid derivatives (ethyl ester and nitrile) with aqueous or gaseous HCl afforded novel 3-substituted 2-oxo-2,5-dihydropyra-no[3,2-b]indoles. 2-Oxo-2,5-dihydropyrano[3,2-b]indole-3-carbonitrile was converted into ethyl 2-oxo-2,5-dihydropyrano[3,2-b]indole-3-carboximidate.     

A one step synthesis of thiadiazolo[2,3-b]quinazoline derivatives

Diazotized anthranilic acid and its methyl ester react with substituted phenacyl thiocyanates 3 to give in both cases the corresponding thiadiazolo[2,3-b]quinazolines 7a-e . A mechanism is proposed and it is substantiated by alternate synthesis of 7a from the hydrazidoyl chlorides 9a,b and potassium thiocyanate.     

Synthesis of condensed quinoxalines

A novel efficient synthesis of fluorescent, fused quinoxalines was achieved. 6-Triazolylthiazolo[4,5-b]quinoxalines were synthesized by the diazotisation of 6-amino-2-methylthiazolo[4,5-b]quinoxaline and coupling with selected aromatic amines followed by air oxidation. Diazotised aryl amines were coupled with 6-amino-2-methylthiazolo[4,5-d]quinoxaline followed by subsequent air oxidation afforded 1,2,3-triazolo[5,4-f]quinoxalino[2,3-d]thiazoles. 6-Amino-2-methylthiazolo[4,5-b]quinoxaline was condensed with conjugated enol ethers followed by cyclization in dowtherm resulted in thiazolo[4,5-b]quinoxalino[6,5-b]pyridine.     

Stereoselective synthesis of the indolizinoindole ring system

We report a novel, facile and stereoselective approach to the indolizino[8,7-b]indole ring system from a readily available, non-racemic chiral template.     

The synthesis of some pyrido[1,4] benzoxazepines and a dipyrido[1,4] oxazepine

Synthetic routes to pyrido[2,3-b]-, pyrido[4,3-b]-, pyrido[3,2-f] [1,4]benzoxazepines and dipyrido[2,3-b:2,3-f] [1,4]oxazepine are described. The applicability of one of the methods to dibenz[b,f] [1,4]oxazepine synthesis is discussed.     

Synthesis of 2,10,11-Trisubstituted Indolo[3,2-b]quinolines

A new method has been developed for the synthesis of derivatives of indolo[3,2-b]quinolines-11 based on N-oxidization of 2-nitro-10-substituted indolo[3,2-b]quinolines with subsequent conversion of the mixtures obtained into 2-nitro-11-substituted indolo[3,2-b]quinolinones-11. A series of 2-nitro-11-substituted indolo[3,2-b]quinolines was prepared.     

Indole and quinoline derivatives of 2,3-dihydro-l-benzothiepin-4(5H) one

By application of the Friedlander synthesis on 2,3-dihydro-l-benzothiepin-4(5H) one (4), the corresponding [4,5-b]quinoline derivatives 5a and 5b were obtained. Starting from the ketone (4) and by application of the Fischer indole synthesis, 1-benzolhiepino[4,5-b ]indole (6) and 1-benzothiepino[4,5-b]benzo[g]indole (7) were obtained. When β-naphthylhydrazine was used in the indolisation reaction, a mixture of 1-benzothiepino[4,5-b]benzo[e]indole ( 8 ) and 1-benzothiepino[4,3-b]benzo[e] indole (9) was obtained.     

Synthesis of triphenyleno[b]thiophenes

The synthesis of all the isomers of triphenyleno[b]thiophenes namely, triphenyleno[l,2-b]thiophene, triphenyleno[2,1-b]thiophene and triphenyleno[2,3-b]thiophene is described.