Compounds in the pyrrolo[3′,4′:4,5] pyrrolo[3,4-b]indole series

Compounds in the new pyrrolo[3′,4′:4,5]pyrrolo[3,4-b]indole series have been produced by an imide cyclization of appropriate derivatives of pyrrolo[3,4-b]indole.     

Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.     

Emission wavelength prediction of a full-color-tunable fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one

In this paper we report on a novel fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one, which we named Seoul-Fluor, having tunable and predictable photophysical properties. Using a concise and practical one-pot synthetic procedure, a 68-member library of new fluorescent compounds was synthesized with diverse substituents. In Seoul-Fluor, the electronic characteristics of the substituents, as well as their positional changes, have a close correlation with their photophysical properties. The systematic perturbation of electronic densities on the specific positions of Seoul-Fluor, guided with the Hammett constant, allows emission wavelength tunability covering the full color range. On the basis of these observations and a computational analysis, we extracted a simple first-order correlation of photophysical properties with the theoretical calculation and accurately predicted the emission wavelength of Seoul-Fluors through the rational design. In this study, we clearly demonstrate that Seoul-Fluor can provide a powerful gateway for the generation of desired fluorescent probes without the need for a tiresome synthesis and trial-and-error process.     

9-Aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one (Seoul-Fluor) as a smart platform for colorful ratiometric fluorescent pH sensors

In this communication, we report that 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one (Seoul-Fluor) can serve as a potential platform for colorful ratiometric fluorescent pH sensors by simple incorporation of pH responsive elements on Seoul-Fluor. Seoul-Fluor-based fluorescent pH sensors allow the emission- and pH-tuning ability upon protonation by varying their pK(a) values and electronic characteristics of substituents by a rational design.     

Unusual formation of a novel pyrrolo[1′,2′:1,2]pyrido[3,4-b]indole

Reaction of 1-methyl-3,4-dihydro-β-carboline 1 with methyl glycidate 4 gave the novel tetracyclic conjugated γ-lactam, 2-methylpyrrolo[1′,2′:1,2]pyrido[3,4–6]indol-3-one 5 . The same compound 5 was obtained in higher yield when 1 was treated with methyl 2-methoxyacrylate 7 . Sodium borohydride treatment of 5 resulted in the cleavage of lactam to yield the unexpected alcohols 8 and 9 .     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene 3. Synthesis of 2,3,6,7-tetrahydro-3-oxobenzo[1,2]cyclohepta[3,4,5-hi]thieno[3,4-c]pyridine and 2,3,7,8-tetrahydro-3-oxothieno[2,1-b]cyclohepta[5,6,7-de]isoquinoline

The title compounds 3 and 4 were synthesized by cyclization via isocyanate of the Z and E-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene-4-ylidenacetic acids 8 and 9 , which in turn were prepared by the Wadsworth-Emmons reaction of ketone 5 with triethyl phosphonacetate followed by separation and independent hydrolysis of the corresponding esters 6 and 7 . The structures of these new compounds as well as the configurations of their isomeric precursors are described.     

Annulation reactions of 3-aminoisoquinolin-l(2H)-one. Synthesis of pyrimido[1,2-b]isoquinolines,pyrido-[2,3-c]isoquinolines and pyrrolo[2,3-c]isoquinolines

Reactions of the title compound with the malonic acid derivatives diethyl ethoxymethylenemalonate (EMME), ethyl ethoxymethylenecyanoacetate (EMCA) and ethoxymethylenemalononitrile (EMMN) are reported. Condensations occur at the amino group or C-4, depending on conditions and the former intermediate was successfully cyclized to the pyrimido[1,2-b]isoquinoline system. Reactions with 2,4-pentanedione and p-bromophenacyl bromide gave only the angular systems, pyrido[2,3-c]isoquinoline and pyrrolo[2,3-c]isoquin-oline, respectively.     

New fused pyrazines. Synthesis of pyrido[3′,2′:4,5]‐thieno[2,3‐e]pyrrolo[1,2‐a]pyrazine derivatives

The synthesis of the title compounds was achieved using the key intermediate ethyl 4,6‐dimethyl‐3‐(pyrrol‐1‐yl)thieno[2,3‐b]pyridine‐2‐ carboxylate 2. This latter compound was obtained via the interaction of the thienopyridine amino ester 1 with 2,5 dimethoxytetrahydrofuran in acidic medium.     

Investigations in the imidazole series LXXIV. Electrophilic substitution reactions in the pyrrolo[1,2-a]imidazole series

The formylation, acetylation, hydroxymethylation, azo coupling, nitrosation, nitration, and chloromercuration of pyrrolo[1,2-a]imidazole derivatives were studied. The PMR spectra were used to establish that all of these reactions proceed at the 5 position or, if it is occupied, at the 7 position of the two-ring system. When the 5 and 7 positions are free, the formation of 5,7-disubstituted pyrrolo[1,2-a]imidazoles is possible.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 405–409, March, 1972.     

The stereochemistry of 1,6,7,12b-Tetrahydro-2H,4H-[1,2] oxazino[3′,4′:1,2]-pyrido[3,4-b]indole and of 1,2,3,6,7,12b-Hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2]pyrido[3,4-6] indole

From an analysis of nmr spectral data, 1,6,7,12b-tetrahydro-2H,4H-[1,3 ]oxazino[3′, 4′ :1,2]-pyrido[ 3,4-b ]indole is shown to exist in solution at room temperature almost entirely in the cis-fused ring conformation with the nitrogen lone pair bisecting the C4 methylene group whereas under the same conditions 1,2,3,6,7,12b-hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2] pyrido-[3,4-b ]indole exists as an approximately 50:50 equilibrium mixture of the cis and trans-fused ring conformations.     

Heterocycles with a benzothiadiazepine moiety. 3. Synthesis of imidazo[5,1-d]pyrrolo[1,2-b][1,2,5]benzothiadiazepine 9,9-dioxide

The synthesis of imidazo[5,1-d]pyrrolo[1,2-b][1,2,5]benzothiadiazepine 9,9-dioxide ( 5 ), a novel sulfur-containing tetracyclic benzodiazepine, is reported starting from pyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-diox-ide ( 6 ) by cycloaddition of tosylmethyl isocyanide to the azomethine double bond. Pyrrolobenzothiadiazepine 6 was obtained by iron powder/acetic acid reduction of 1-(2-nitrobenzenefulfonyl)pyrrole-2-carboxaldehyde ( 7 ) and subsequent ring closure of intermediate aminoaldehyde or by cyclization of 1-(2-formamidobenzene-sulfonyl)pyrrole ( 8 ) with phosphorus oxychloride via a Bischler-Napieralski reaction. Formylation of 1-(2-ami-nobenzenesulfonyl)pyrrole with acetic-formic anhydride gave 8. The structure of 5 was confirmed by oxidation with activated manganese dioxide of dihydro derivative 9 , obtained through cyclization of 11-amino-methyl-10,11-dihydropyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxide ( 10 ) with triethyl orthoformate. The last compound was prepared alternatively by catalytic reduction of nitro derivative 11 , obtained by addition of nitromethane to pyrrolobenzothiadiazepine 6 , or by lithium aluminum hydride/sulfuric acid reduction of amide 13 , synthesized starting from ethyl 10,11-dihydropyrrolo[1,2-b][1,2,5]benzothiadiazepine-11-carboxyl-ate 5,5-dioxide.     

Generation of pyrrolo[2,1‐a]isoquinoline derivatives from N‐ylides: Synthetic control and structural characterization

New pyrrolo[2,1‐a]isoquinolines were obtained by two one‐pot procedures via 1,3‐dipolar cycloaddition between the isoquinolinium N‐ylides and symmetrical acetylenic dipolarophiles, avoiding the formation of dihydro intermediates. For structural comparison, the dihydro derivatives obtained by a classical two‐stage reaction were characterized by NMR and X‐ray crystallography, allowing complete stereochemistry assignments. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:723–729, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/.20740     

Synthesis of 1,2,3,12a,12b‐Hexahydrocyclopropa‐[1,2‐d]benzo[f]pyrrolo[1,2‐b]isoquinolin‐5,7‐dione related to duocarmycins and anthramycin

Structural features of the Duocarmycins and Anthramycin were incorporated into 1,2,3,12a,12b‐hexahydro‐cyclopropa[1,2‐d]benzo[f]pyrrolo[1,2‐b]isoquinolin 5,7‐dione. The synthesis of the cis and trans diastereomers was accomplished using a benzyne Diels‐Alder reaction and an imine‐anhydride cyclization as key steps.     

Stereospecific fragmentation processes in cycloalkane/cycloalkene-fused isomers of saturated pyrrolo[2,1-b][1,3]oxazin-6-one derivatives

Electron ionization-induced fragmentations were studied in a set of saturated pyrrolo[2,1-b][1,3]oxazin-6-one derivatives fused to either cycloalkane or cycloalkene rings, including seven pairs of cis/trans and endo/exo annelation isomers. Fragmentation patterns were confirmed by accurate mass measurements and metastable ion spectra. A number of striking differences were observed between the mass spectra of cyclohexene-fused isomers due to highly stereospecific retro-Diels-Alder (RDA) fragmentation of their M^+· ions. The observed 90% stereospecificity is abnormally high in the light of the recent classification (A. Mandelbaum, 1994) of stereospecific RDA fragmentations according to the degree of substitution of the cyclohexene ring being cleaved. In the absence of RDA processes, the differences between the mass spectra of cyclohexane-fused isomers originated from heterocyclic fragmentations. The assumed mechanistic interpretation of the observed differences, e. g., in the formation of [M − C₃H₅O]⁺ ions, was consistent with the condensed-state conformations of these isomers determined previously by NMR and X-ray diffraction studies. Because of rapid RDA decompositions of their rather unstable M^+· ions, the spectra of the diendo/diexo norbornene-fused isomers were virtually identical.