The isolation and structure determination of cryptomisrine,a novel indolo[3,2-b]quinoline dimeric alkaloid from cryptolepis sanguinolenta

The isolation and structure determination of cryptomisrine, a novel indolo[3,2-b]quinoline dimeric alkaloid obtained from extracts of the roots of the Ghanaian medicinal plant Cryptolepis sanguinolenta is reported. The structure determination was made via a consideration of the spectral data, including uv, ir, nmr, and mass spectra. In particular, one-dimensional proton/carbon nmr, one-dimensional nOe difference nmr, and a series of homonuclear (COSY) and inverse-detected heteronuclear two-dimensional (HMQC, HMBC) experiments were utilized, as well as high resolution FABMS. Cryptomisrine is most unusual in that its two monomeric parts apparently exist in such a C₂ symmetric environment that only one set of proton and carbon nmr resonances are observed. Cryptomisrine is the first example of a dimeric indolo-[3,2-b]quinoline alkaloid to have been isolated from nature.     

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.     

Study of Friedel-Crafts acetylation of indolobenzo[b]furans,indolobenzo[b]thiophenes,pyrrolocarbazole, and pyrrolophenothazine dioxide by1H NMR spectroscopy

The reactivity towards Friedel-Crafts acetylation of the new heterocyclic systems indolo[5,6-d]- and indolo[5,4-d]benzo-[d]furans, 3H pyrrolo[2,3-c]carbazole, indolo[7,6-d]-, indolo[4,5-d]- and indolo[5,4-d]benzo-[b]thiophenes and 3H-pyrrolo[2,3-c]phenothiazine-11,11-dioxide have been studied. Under acid conditions these heterocycles behave like indole to give dimerization products, but anomalies were observed in a number of cases. These principles have been established by detailed analysis of the ¹ H NMR spectra of the reaction products. Georgian Technical University, Tbilisi 380075. D. I. Mendeleev Russian Chemical Technological University, Moscow 125047. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1078–1091, August, 1995. Original article submitted June 12, 1995.     

Revisiting Indolo[3,2-b]carbazole: Synthesis,Structures, Properties,and Applications

Indolo[3,2-b]carbazole presents a π-skeleton with a remarkable electronic structure and interesting potential applications. It is, however, also associated with ambiguity and controversy. Herein, new derivatives of indolo[3,2-b]carbazole are reported and they have enabled a comprehensive study on the electronic structure of indolo[3,2-b]carbazole and the development of a new n-type organic semiconductor. Experimental and computational studies show that indolo[3,2-b]carbazole has a largely localized p-benzoquinonediimine moiety and significant antiaromaticity. When substituted with (4-silylethynyl)phenyl groups, the indolo[3,2-b]carbazole exhibits one-dimensional π–π stacking and functions as an n-type organic semiconductor in solution-processed field effect transistors.     

Synthesis of tryptanthrin (couroupitine) derivatives by reaction of substituted isatins with phosphoryl chloride

Reaction of 5-methyl-, 5-bromo-, and 5-iodoisatins with phosphoryl chloride gave the corresponding 2,8-disubstituted indolo[2,1-b]quinazoline-6,12-diones in moderate yield. 5,7-Dichloroisatin failed to react with POCl₃. Treatment of an equimolar mixture of isatin and 5-bromoisatin with POCl₃ afforded indolo[2,1-b]-quinazoline-6,12-dione (tryptanthrin), 2,8-dibromoindolo[2,1-b]quinazoline-6,12-dione, and two isomeric monobromo-substituted tryptanthrin derivatives, the 2-bromo isomer prevailing.     

Action of 1,2-diamines and o-aminophenols on 1-alkyl-3-carboxyindole-2-acetic acid anhydrides. Preparation of new ring systems

1-Alkyl-3-carboxyindole-2-acetic acid anhydrides (I) react with ethylenediamine and with o-phenylenediamine to give directly 10-alkylimidazo[3,2:1′,2′]pyrido[4,5-b]indol-5(1H)-ones (II) and 5,6-dihydro-5-alkyl-13H-indolo[2′,3′:4,5]pyrido[1,2-a]benzimidazol-13-one (V), respectively. However, anhydrides I react with o-aminophenol and with o-aminothiophenol to give carboxyindole-acetanilide derivatives IX, which can be cyclised to indolo[2′,3′:4,5]pyrido[2,1-b]benzoxazolone and indolo[2′,3′:4,5]pyrido[2,1-b]benzthiazolone (XI). Some derivatives of II and V were prepared to help in elucidating the structures.     

A new approach to the synthesis of pyrido[4,3-<Emphasis Type="Italic">b</Emphasis>]indole derivatives (γ-carbolines) <Emphasis Type="Italic">via</Emphasis> cyclization of enamino dinitriles

Reactions of 2-dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole with various amines afforded enamino dinitriles and the corresponding pyrido[4,3-b]indoles (γ-carbolines). 3-Amino-4-cyano-5H-pyrido[4,3-b]indole reacted with cyclohexanone to give pentacyclic 13-amino-2,3,4,12-tetrahydro-1H-benzo[b]indolo[2,3-f]-1,8-naphthyridine. Alkylation of pyrido[4,3-b]indoles with various alkylating agents was studied.     

Synthetic applications of 2-chloro-3-formylquinoline

New examples of synthetic applications of 2-chloro-3-formylquinoline, as evident from the novel and facile syntheses of 3-aminoisooxazolo[5,4-b]quinoline (4), 3-hydroxyfuro[2,3-d]theino[2,3-b]quinoline-2-carboxamide (7) and 3-hydroxymethyl-2-(3-formyl)phenylquinoline ( 13 ), have been furnished.     

Acetylation of indolobenzo[b]furans,pyrrolocarbazole, pyrrolophenothiazine dioxide and pyrroloacridine under Vilsmeier reaction conditions

The course of the Vilsmeier acetylation of new heterocyclic systems, namely, indolo[4,5-d]-, indolo[6,5-d]-, indolo[5,6-d]-, indolo[5,4-d]benzo[b]furans, 3H-pyrrolo[2,3-c]carbazole, 3H-pyrrolo[2,3-c]pheno-thiazine 11,11-dioxide, and 3H-pyrrolo[2,3-c]acridine depends on the type of fusion of the pyrrole ring. Angular heterocycles are acetylated at the -position of the pyrrole ring, while linear heterocycles under analogues conditions give dimerization products with a substituent at the nitrogen atom of the hydrogenated part of the dimer molecule. 3H-Pyrrolo[2,3-c]phenothiazine 11,11-dioxide and 3H-pyrrolo[2,3-c]acridine are not acetylated under Vilsmeier reaction conditions.Georgian Technical University, 380075 Tbilisi, Georgia. D. E. Mendeleev Russian Chemical Engineering University, 125047 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1331–1336, October, 1996. Original article submitted August 19, 1996.     

Highly Diastereoselective Synthesis of Polycyclic Indolines through Formal [4+2] Propargylic Cycloaddition of Indoles with Ethynyl Benzoxazinanones

A formal [4+2] propargylic annulation of indoles and pyrrole with ethynyl benzoxazinanones was described. This protocol provides a concise synthesis of tetrahydro‐5H‐indolo[2,3‐b]quinolines and tetrahydro‐3H‐pyrrolo[3,2‐b]quinoline, the core structures of alkaloid frameworks, featuring excellent yields, high diastereoselectivity, mild conditions and wide substrate scope.     

Synthesis of 7-methyl-4,6,6a,7,10,10a-hexa-hydroindolo[4,3-fg]quinazoline derivatives

The synthesis of a series of compounds indolo[4,3-fg]quinazoline related to ergoline (indolo[4,3-fg]quinoline) is reported. The key step of the synthetic sequence is the ring cleavage of the ketone IV. The stereochemistry of the chiral centers is established by the chirality of dihydrolysergic acid I.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

Quino[1,2-c]quinazolines. I. Synthesis of quino[1,2-c]quinazolinium derivatives and the related indazolo[2,3-a]quinoline derivatives as analogs of the antitumor benzo[c]phenanthridine alkaloids

9,10-Dimethoxy-1,2,3,4,12,13-hexahydro-1-oxoquino[1,2-c]quinazolinium perchlorate, 1,2,3,4,13,24-hexahydro-1-oxo[1,3]dioxolo[4,5-g]quino[1,2-c]quinazolinium perchlorate, 6-methyl-2,3,9,10-tetramethoxyquino-[1,2-c]quinazolinium perchlorate and 2,3-dimethoxy-13-methyl[1,3]dioxolo[4′,5′:6,7]quino[1,2-c]quinazolinium perchlorate were synthesized as analogs of the potent antitumor benzo[c]phenanthridine alkaloids nitidine and fagaronine. The related 2,3,8,9-tetramethoxyindazolo[2,3-a]quinoline and 2,3-dimethoxy[1,3]dioxolo-[4,5-g]indazolo[2,3-a]quinoline were also synthesized. Further, the novel formation of 6,7-dimethoxy-2-(2-ethylamino-4,5-dimethoxyphenyl)quinoline via reductive alkylation with Raney nickel in refluxing ethanol is also reported.     

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyrimido[4′,5′:4,5]theino[2,3-b]quinoline and pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyriraido[4′,5′:4,5]theino[2,3-b]quinoline and 12-phenylpyrido[1′,2′:1,2[pyrimido[4,5-b]quinoline are described.     

Structure elucidation of two tryptophan-derived, high affinity Ah receptor ligands

Background: Environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other structurally related ‘environmental hormones’, exert their harmful biological effects through the Ah receptor signaling pathway. Several naturally occurring substances also bind to this receptor, but its natural role is still obscure. Tryptophan derivatives of the indolo[3,2-b]carbazole type, earlier suggested by us to be endogenous ligands for the receptor, should be a powerful tool in understanding receptor function. We therefore: set out to determine their identity.Results: The two tryptophan-derived Ah receptor ligands have been chemically analyzed and characterized by means of mass spectrometry, ¹H NMR and ¹³C NMR. UV, infra-red and fluorescence spectra were also recorded. All data are in accordance with the two compounds being closely related indolo[3,2-b]carbazole derivatives. Evidence is presented that compound A (MW = 312) is the symmetrical 6,12-diformylindolo[3,2-b]carbazole, and compound B (MW = 284) is the monosubstituted 6-formylindolo[3,2-b]carbazole.Conclusions: The elucidation of the structures of the two high affinity Ah receptor ligands 6,12-diformylindolo[3,2-b]carbazole and 6-formylindolo[3,2-b]carbazole provides the necessary basis for further mechanistic studies of this important group of compounds, and will help in determining the natural role of the Ah receptor.     

Synthesis,photophysical and electrochemical properties of novel 6,12-di(thiophen-2-yl) substituted indolo[3,2-b]carbazoles

Novel 5,11-dialkyl-6,12-di(thiophen-2-yl) substituted 5,11-dihydroindolo[3,2-b]carbazoles have been obtained and plausible ways for their further modifications via the Friedel–Crafts reaction are presented. The formylation of these indolo[3,2-b]carbazoles with dichloromethyl alkyl esters catalysed by Lewis acids leads to the formation of the corresponding 2,8-diformyl derivatives. Applicability of this formylation method for modification of indolo[3,2-b]carbazoles bearing electron-rich aromatic substituents at C-6 and C-12 has also been demonstrated. The Knoevenagel condensation of 2,8-dialdehydes with active methylene nitriles has been studied. The measurements of optical and redox properties for a number of new indolo[3,2-b]carbazoles have been performed.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 5. [1]Benzothieno[2,3-c]naphtho[2,1-f]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline

Two previously unknown heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[2,1-f]quinoline ( 4 ) and [1]benzothieno[2,3-c]naphtho[1,2-g]quinoline ( 5 ) were synthesized via photocyclization of 3-chloro-N-(2-phenanthryl)benzo[b]thiophene-2-carboxamide ( 8 ) followed by chlorination and dechlorination. The total assignment of their ¹H- and ¹³C-nmr spectra was determined by utilizing inverse-detected HMQC and HMBC two-dimensional nmr spectroscopic methods.     

The synthesis of the monomethyl isomers of benzo[b]naphth[2,1-d]thiophene

All isomers of the monomethylbenzo[b]naphth[2,1-d]thiophenes were synthesized using photocyclization of 3-styrylbenzo[b]thiophenes. The 1-, 3-, 4-, and 5-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by irradiation of the corresponding methylated 3-styrylbenzo[b]thiophenes which were prepared by the Wadsworth-Emmons reaction of diethyl benzo[b]thenylphosphonate with o-, m-, p-tolualdehyde and acetophenone. The 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophenes were synthesized by decarboxylation of 7-, 8-, 9- and 10-methylbenzo[b]naphtho[2,1-d]thiophene-6-carboxylic acid with copper in quinoline. These carboxylic acids were prepared by photocyclization of the corresponding 2-(benzo[b]thiophen-3-yl)-3-phenylpropenoic acids which were prepared by the condensation of the methylated benzo[b]thiophene-3-ylacetic acids with benzaldehyde in the presence of triethylamine in acetic anhydride.     

New formal (3+3) cycloaddition of enaminones for forming tetracyclic indolo[2,3-b]quinolines under microwave irradiation

Concise and efficient base-promoted domino formal (3+3) cycloaddition has been established for the formation of tetracyclic indolo[2,3-b]quinoline derivatives under microwave heating. The present methodology shows attractive properties, such as the maximum efficiency of a process, short reaction periods, and operational simplicity, and it can avoid time-consuming and costly syntheses, tedious work-up and isolation of intermediate. This chemistry provides a facile and promising synthetic strategy to construction of tetracyclic indolo[2,3-b]quinoline skeleton.     

Synthesis of novel heterocycles from 2-amino-3-cyanomethyl-sulfonyl-4,5-dimethylfuran

The synthesis and selected reactions of the versatile heterocycle 2-amino-3-cyanomethylsulfonyl-4,5-dimethylfuran is reported. In particular, cyclization reaction of the aminofuran yielded a number of novel furo[3,2-b]thiazine 1,1-dioxides. Additionally, a novel tetracyclic system, namely a pyrrolo[2′,3′:5,6]-[1,4]thiazino[3,2-b]quinoline 4,4-dioxide, is prepared via an intramolecular triple-cyclization in which the furan ring is opened and reclosed as a pyrrole.