Synthesis and nitration of some thieno-fused analogues of the benzo[a]quinolizinium cation

Three thieno-fused analogues of benzo[a]quinolizinium ( 1 ), thieno[3,2-a]- and thieno[2,3-a]quinolizinium 4 and 5 and thiazolo[2,3-a]isoquinolinium ( 6 ), were synthesized by photocyclization of 1-(2-thienylvinyl)pyridinium salts 9a and 9b and 3-styrylthiazolium salt 9c , respectively. The nitration of the compounds 4, 5 , and 6 occurred predominantly at positions 2, 3, and 7, respectively, while the nitro group was introduced into the 8- and 10-positions of 1 in the ratio of 68:32. The nmr and uv spectral properties and reduction potentials of 4–6 were also compared with those of the parent compound 1 .     

Synthesis and reactions of methylbenzo[c]quinolizinium salts

Six isomers of the methylbenzo[c]quinolizinium salt 3 including four new monomethyl derivatives were synthesized by thermal-intramolecular quaternization of the cis-methyl-substituted 2-[2-(2-chlorophenyl)-vinyl]pyridines 4 or by the irradiation of trans- 4 with selected wavelengths (290 < λ < 340 nm and λ > 400 nm) in acetonitrile. Among the regioisomeric monomethyl derivatives 3 , the 1-, 3-, and 6-methyl derivatives 3b, 3d , and 3g reacted with p-methoxybenzaldehyde in the presence of bis(l-piperidino)-(p-methoxyphenyl)-methane 7 to yield trans-(p-methoxystyryl)benzo[c]quinolizinium salts 6 . The reactivity of 3 and methylbenzo[a]quinolizinium salts 1 was discussed on the basis of their π-electron energy.     

Comparative study on the structural, optical, and electrochemical properties of bithiophene-fused benzo[c]phospholes

Three types of bithiophene-fused benzo[c]phospholes were successfully prepared by Ti(II)-mediated cyclization of the corresponding dialkynylated bithiophene derivatives as a key step. Each sigma(3)-phosphorus center of the benzo[c]phosphole subunits was readily transformed into sigma(4)-phosphorus center by Au coordination or oxygenation. In addition, the bithiophene subunit was functionalized at the alpha,alpha'-carbon atoms by Pd-catalyzed cross-coupling reactions with heteroarylmetals and by an S(N)Ar reaction with hexafluorobenzene. The experimentally observed results (NMR spectroscopy, X-ray analysis, UV/Vis absorption/fluorescence spectroscopy, and cyclic/differential-pulse voltammetry) have revealed that the structural, optical, and electrochemical properties of the bithiophene-fused benzo[c]phospholes vary considerably depending on the pi-conjugation modes at the bithiophene subunits and the substituents of the heterocyclopentadiene components. The appropriately ring-annulated sigma(3)-P derivatives and sigma(4)-P-AuCl complexes were found to emit fluorescence in the orange-red region, and the sigma(4)-P-oxo derivatives proved to undergo reversible one-electron reduction at -1.4 to -1.8 V (vs ferrocene/ferrocenium). These results indicate that the bithiophene-fused benzo[c]phospholes possess narrow HOMO-LUMO gaps and low-lying LUMOs, which was confirmed by density functional theory calculations of their model compounds. The time-of-flight measurement of an ITO/benzo[c]phosphole/Al device showed that the electron mobility in the P-oxo derivative is one-order higher than that in Alq(3) at low electric fields. The present study demonstrates that the arene-fused benzo[c]phosphole skeleton could be a highly promising platform for the construction of a new class of phosphole-based optoelectrochemical materials.     

Synthesis of benzo[c]phenanthrene dihydrodiols

Unlike most other alternant polycyclic aromatic hydrocarbons which are carcinogenic, benzo[c]phenanthrene has a “fjord region” instead of a “bay region”. For this reason, we have synthesized the three metabolically possible trans 1,2-, 3,4-, and 5,6-dihydrodiols to test them for carcinogenic activity.     

Synthesis of benzo[4,5]phenaleno[1,9-bc]thiophene and benzo[4,5]phenaleno[9,1–6c]thiophene

Two pentacyclic thiophenes, benzo[4,5]phenaleno[1,9–6c]thiophene ( 1 ) and benzo[4,5]phenaleno[9,1-bc]-thiophene (2) were synthesized via the corresponding 3-methylphenanthro[2,1-b]thiophene (7) and 1-methylanthra[2,1–6]thiphene ( 19 ).     

The synthesis of benzo[c]cinnoline 5,6-dioxides and related compounds

The preparation of a variety of benzo[c]cinnolines as well as benzo[c]cinnoline monoxides and dioxides by reduction of the corresponding 2,2-dinitrobiphenyls with hydrogen and Raney nickel of low activity is described. The detailed procedures developed produce superior yields of benzo[c]cinnoline monoxides and dioxides. The structure of some intensely-colored red-violet amino, alkylamino, and hydroxybenzo[c]cinnoline monoxides and dioxides is discussed and these are compared with the essentially colorless alkoxyl and acetylamino derivatives. The long wave length band in the U. V. spectrum of the colored compounds is compared.     

Synthesis and physicochemical characterization of novel 6-aminopyrido[3,4-c][1,9]phenanthrolines as aza-analogs of benzo[c]phenanthridines

Based on the 6-aminobenzo[c]phenanthridines, a compound class showing noteworthy antitumor activity, an efficient one-step synthesis consisting of a base-catalyzed condensation of 2 equiv of 4-methylpyridine-3-carbonitrile and various aldehydes causing twofold ring closure is described. The obtained 6-amino-11,12-dihydropyrido[3,4-c][1,9]phenanthrolines could be aromatized with Pd/C at high temperatures to form 6-aminopyrido[3,4-c][1,9]phenanthrolines. All compounds were systematically characterized regarding both lipophilicity and solubility and a high cytotoxic potential was evaluated in preliminary in vitro studies. Compared to formerly described 6-aminobenzo[c]phenanthridines our newly developed phenanthrolines turned out to possess improved drugability, due to significantly increased water-solubility and decreased lipophilicity.     

Synthesis and spectroscopic properties of novel benzo[a]phenanthridines

Condensation of arylidene-2-naphthylarnines with 5,5-dimethylcyclohexane-1,3-dione (dimedone) gives novel 2,2-dimethyl-5-R-1,2,3,4,5,6-hexahydrobenzo[a]phenanthridin-4-ones. Treatment of azomethines containing an ortho hydroxyl group in the aldehyde fragment gives the corresponding 3,3,6,6-tetramethyl-9-R-1,2,3,4,5,6,7,8-octa-hydroxanthene-1,8-diones. The IR, UV, PMR, and mass spectra of the compounds synthesized have been studied.     

Synthesis and in vitro cytotoxic evaluation of N-substituted benzo[5,6]cycloheptal[b]indoles

A new series of V-substituted benzo[5,6]cyclohepta[b]indole derivatives were synthesised and evaluated for in vitro cytotoxic activities against L1210 murine leukemia and HT29 cell lines. Among them, several compounds showed potent antitumor activity and blocked cell cycle progression of L1210 cells in G2+M phase.     

Synthesis and cytotoxic activity of benzo[a]pyrano[3,2-h] and [2,3-i]xanthone analogues of psorospermine, acronycine, and benzo[a]acronycine

Condensation of 2-hydroxy-1-naphthalenecarboxylic acid with phloroglucinol afforded 9,11-dihydroxy-12H-benzo[a]xanthen-12-one (6). Construction of an additional dimethylpyran ring onto this skeleton, by alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement, gave access to 6-hydroxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (12) and 5-hydroxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (13), which were methylated into 6-methoxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (14) and 5-methoxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (15), respectively. Osmium tetroxide oxidation of 14 and 15 gave the corresponding (+/-)-cis-diols 16 and 17, which afforded the corresponding esters 18-21 upon acylation. Similarly, condensation of 2-hydroxy-1-naphthalenecarboxylic acid with 3,5-dimethoxyaniline gave 11-amino-9-methoxy-12H-benzo[a]xanthen-12-one (23) which was converted into 11-amino-9-hydroxy-12H-benzo[a]xanthen-12-one (24) upon treatment with hydrogen bromide in acetic acid. Alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement afforded 6-amino-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (25) and 5-amino-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (26). The new benzopyranoxanthone derivatives only displayed marginal antiproliferative activity when tested against L1210 and KB-3-1 cell lines. The only compounds found significantly active against L1210 cell line, 16 and 20, belong to the benzo[a]pyrano[3,2-h]xanthen-7-one series, which possess a pyran ring fused angularly onto the xanthone basic core.     

Synthesis and structural,spectroscopic, and electrochemical characterization of new ruthenium dimethyl sulfoxide nitrosyls

The reactivity of ruthenium(II)- and ruthenium(III)-chloride-dimethyl sulfoxide precursors and of the antimetastatic drug [ImH][trans-RuCl(4)(dmso-S)(Im)] (NAMI-A, Im = imidazole, dmso = dimethyl sulfoxide) toward NO was investigated. Treatment of [(dmso)(2)H][trans-RuCl(4)(dmso-S)(2)] and mer-RuCl(3)(dmso)(3) with gaseous NO yielded [(dmso)(2)H][trans-RuCl(4)(dmso-O)(NO)] (1) and mer,cis-RuCl(3)(dmso-O)(2)(NO) (2), respectively. Thus, coordination of the strong pi-acceptor NO induces a S to O linkage isomerization of the dmso trans to it to avoid competition for pi-electrons. In light-protected nitromethane solutions, complex 2 equilibrates slowly with the two isomers mer-RuCl(3)(dmso-S)(dmso-O)(NO) (3), with NO trans to Cl, and mer-RuCl(3)(dmso-S)(dmso-O)(NO) (4), with NO trans to dmso-O; the equilibrium mixture consists of ca. 64% 2, 3% 3, and 33% 4. Treatment of the Ru(II) precursor trans-RuCl(2)(dmso-S)(4) with gaseous NO in CH(2)Cl(2) solution yielded the nitrosyl-nitro derivative trans,cis,cis-RuCl(2)(dmso-O)(2)(NO)(NO(2)) (5). Finally, [(Im)(2)H][trans-RuCl(4)(Im)(NO)] (6) was prepared by treatment of [ImH][trans-RuCl(4)(dmso-O)(NO)] (1Im) with an excess of imidazole in refluxing acetone. The spectroscopic features are consistent with the [Ru(NO)](6) formulation for all complexes, that is, a diamagnetic Ru(II) nucleus bound to NO(+). Compounds 1, 2, 5, and 6 were characterized also by X-ray crystallography; they all show a linear nitrosyl group, with short Ru-NO bond distances consistent with a strong d(pi) --> pi NO back-bonding. An unusual inertness of O-bonded dmso was observed in compound 1. Complexes 1, 2, 3, 5, and 6 are all redox active in DMF solutions showing irreversible reductions whose peak potentials depend on the other ligands attached to the Ru metal center. The site of reduction is the NO(+) moiety. The reduced complexes are not stable and release a Cl(-) or NO(2)(-) ligand followed by the NO(*) radical. The chemical reactions following electron transfer are all fast (rate constant >100 s(-1) at 293 K). The Ru product species are not redox active within the DMF window.     

Synthesis and cytotoxic activities of a new benzo[c]phenanthridine alkaloid, 7-hydroxynitidine, and some 9-oxygenated benzo[c]phenanthridine derivatives

[formula: see text] A new benzo[c]phenanthridine alkaloid, 7-hydroxynitidine, was synthesized by a novel synthetic procedure. The cytotoxic activity of this compound against HeLa S3 cells was strong, but not greater than those of its mother compounds, nitidine and NK109. We also synthesized other 9-oxygenated benzo[c]phenanthridine alkaloids, 7-methoxynitidine, 9-demethylnitidine, nitidine, and fagaronine, and tested their cytotoxic activities. These results suggest that the 7-hydroxy group enhances antitumor activity and an 8- or 9-hydroxy group weakens this activity.     

Synthesis of benzo[c][1,7]naphthyridine derivatives

Chemistry of Heterocyclic Compounds - Reactivity of 2-methyl-6-phenylbenzo[c][1,7]naphthyridine in alkylation, oxidation, and electrophilic substitution reactions has been studied. The reaction of...     

Synthesis of functionally substituted benzo[c]pyrylium salts

Benzo[c]pyrylium salts that contain an acetyl, cyano, or ethoxycarbonyl group in the 4 position of the pyrylium ring were synthesized by the reaction of 3-(3,4-dimethoxyphenyl)pentane-2,4-dione and -(3,4-dimethoxyphenyl)acetoacetonitrile and ethyl -(3,4-dimethoxyphenyl)acetoacetate, as well as ethyl -(3,4-dimethoxyphenyl)benzoylacetate, with acyl perchlorates. It is shown that -(3,4-dimethoxyphenyl)acetoacetonitrile ethyleneketal is converted to 3-amino-4-acetylbenzo(c)pyrylium salts under these conditions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 465–470, April, 1990.     

Synthesis and reaction of methylbenzo[a]quinolizinium salts

All isomers of (monomethyl)benzo[a]quinolizinium salts including five new monomethyl derivatives were prepared by photocyclization, sulfur extrusion, or cyclodehydration reaction, and their aldol-type condensation was examined. The 2- and 4-methyl derivatives 3b and 3c reacted with p-methoxybenzaldehyde in the presence of piperidine to yield trans-(p-methoxystyryl)benzo[a]quinolizinium salts 11 . The other methyl derivatives did not react with the aldehyde. The methyl group was reactive at the 2- and 4-positions, located para and ortho to the azonia ring nitrogen, respectively; however, it was unreactive at the 6-position located at another ortho position.     

Synthesis of 5-amino-1,2,3,4-tetrahydrobenzo[b][1,7]naphthyridines and 2,3,4,4a,5,6-hexahydrobenzo[c][2,6]naphthyridines

This paper describes the synthesis of some 5-amino-1,2,3,4-tetrahydrobenzo[b][1,7]naphthyridines and 2,3,4,4a,5,6-hexahydrobenzo[c][2,6] naphthyridines starting from anilines and 1-benzyl-4-ethoxycarbonylpiperidin-3-one. The compounds were prepared in order to study their potential acetylcholinesterase inhibitory activity.     

Synthesis of benzo[c]selenophene and derivatives via new routes

[reaction: see text] Benzo[c]selenophene has been generated via facile bromination-dehydrobromination as well as oxidation of the 1,3-dihydrobenzo[c]selenophene. Benzo[c]selenophene thus generated has been lithiated in situ and treated with ClCOOEt to give the first functionalized derivative subject to X-ray crystallographic analysis.