Benzo-fused bicyclic imides

Pavia, Michael R.; Moos, Walter H.; Hershenson, Fred M.

doi:10.1021/jo00289a031

Cited by 30 publications

(19 citation statements)

References 1 publication

(1 reference statement)

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“…39,40) But it failed in our case largely due to the poor solubility of both substrates and products in refluxing acetic anhydride. Fortunately, the intramolecular N-acylation of 8a was achieved successfully in almost quantitative yield by refluxing it in xylene for 8 h with a Dean-Stark trap.…”

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confidence: 75%

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

Wang

Cao

Shi

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Recently, A-ring alkoxyl subsitituted b-carbolin-1-ones (1, Chart 1) were reported to inhibit colon and lung tumors in a patent literature.1) Subsequently, we found that 3-aryl b-carbolin-1-ones (2) inhibit the proliferation of HeLa cells with IC 50 values in the low micromolar range and that the aromatic substitution on C3 in 2 proved to be essential for their biological activity.2,3) To broaden the scope of previous studies, aryl-substituted 2-pyridone-containing derivatives, such as pyrido[2,1-a]isoindole-4-one (3) and 1H-indeno[1,2-b]pyridine-2-one (4), were designed as our synthetic targets to make it possible to probe their structure-activity relationships.Some alkaloids having frameworks of 3 and 4 occur in nature, 4-7) whose analogues were synthesized more often in laboratories for their potent bioactivities as receptor ligands, [8][9][10] enzyme inhibitors 11) or anti-tumor agents.12,13)Since 3 and 4 are a pair of structural isomers, it is reasonable to expect that they could be prepared from a common precursor, which should have a structure of 6-substituted 2-pyridone allowing a disconnection between methylene and Cring in 3 and 4 (Chart 1). However, neither such precursor nor procedure has been employed for this purpose so far. [14][15][16][17][18][19][20][21][22][23][24][25][26] Since the methods for preparation of 3-unsubstituted 2-pyridone have been well established in recent years, 27-37) herein we report a novel synthetic route to 3 and 4 as shown in Chart 2. The route starts from an aldol condensation between 2-acetylbenzoic acid (5) and aryl aldehyde (6) to yield chalcone (7), which subsequently undergoes a [3ϩ3] annulation to give 2-(2-pyridon-6-yl)benzoic acid (8). Serving as a common precursor, 8 goes through an intramolecular N-acylation to produce 2-aryl pyrido[2,1-a]isoindole-4,6-diones (9), or carries out an intramolecular C-acylation to yield 4-aryl 1-methyl-1H-indeno[1,2-b]pyridine-2,5-diones (11) regioselectively. Results and DiscussionPreparation of 2-Aryl Pyrido[2,1-a]isoindole-4,6-diones (9a-j) Following the known procedure, 38) the mixtures of 2-acetylbenzoic acid (5) and aryl aldehydes 6a-j were treated respectively with NaOH in aqueous EtOH at room temperature for 20 h. As shown in Table 1, the corresponding products 2-(3-aryl acryloyl)benzoic acids (7a-j) were yielded conveniently in high yields. However, the aryl aldehydes bearing an electron-withdrawing group, such as o-, m-, A novel and practical preparation of 2-pyridone-containing tricyclic alkaloid derivatives was developed. By regioselective intramolecular N-and C-acylation of 2-(4-aryl-2-pyridon-6-yl)benzoic acid, a pair of structural isomers 2-aryl pyrido[2,1-a]isoindole-4,6-diones and 4-aryl 1-methyl-1H-indeno[1,2-b]-pyridine-2,5-diones, as potential inhibitors of tumor cell proliferation, were prepared respectively.

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confidence: 75%

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

Wang

Cao

Shi

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…44 Treatment of this diol with excess R-bromoisobutyryl bromide in the presence of triethylamine yielded compound 1 in 83% yield after purification. ATRP of tBA from 1 using CuBr catalyst, PMDETA ligand, and toluene solvent yielded R,ω-bromo-ptBA, 2, possessing the NBOC functionality at its center (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Photocleavable Linear Macromonomers by ATRP and Star Macromonomers by a Tandem ATRP−Click Reaction: Precursors to Photodegradable Model Networks

et al. 2007

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Atom transfer radical polymerization (ATRP) and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) were utilized for the synthesis of photodegradable polymeric materials by two complementary schemes. Linear azido-telechelic macromonomers possessing a photocleavable functionality at the center were synthesized by ATRP and subsequent end-group modification. These macromonomers were cross-linked with a tetrafunctional alkyne by CuAAC to form insoluble materials which degraded upon exposure to UV light of 350 nm to yield soluble star polymer products of defined molecular weight. Complementary to this approach, four-armed star polymers possessing photocleavable arms and terminal azides were prepared by a novel one-pot CuAAC/ATRP reaction followed by end-group modification. These star polymers were cross-linked with a linear, bifunctional alkyne to yield insoluble materials which, upon exposure to UV light, degraded to yield linear polymers of defined molecular weight.

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“…Following the literature procedure [18] (with necessary modifications), the NBU compound was first obtained by reacting 2-nitro-1,3-benzenedimethanol (NBDM, synthesized in our laboratory using the reported procedure [19]) with two molar excess of tolylene 2,4-diisocyanate (TDI, purity > 95%, Sigma-Aldrich) in anhydrous dimethylformamide (DMF, purity 99.8%, Sigma-Aldrich). Briefly, NBDM (110 mg, 0.60 mmol) was charged into a flask, and dissolved in anhydrous DMF (10 ml) under slight heating at 60 °C for 1 h. The flask was then cooled down to 0 °C in ice bath, and kept under protection from light using aluminum foil.…”

Section: Methodsmentioning

confidence: 99%

A photo-degradable gene delivery system for enhanced nuclear gene transcription

et al. 2014

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There currently exists a significant gap in our understanding of how the detailed chemical characteristics of polycation gene carriers influence their delivery performances in overcoming an important cellular-level transport barrier, i.e., intranuclear gene transcription. In this study, a UV-degradable gene carrier material (ENE4-1) was synthesized by crosslinking low molecular weight branched polyethylenimine (bPEI-2k) molecules using UV-cleavable o-nitrobenzyl urethane (NBU) as the linker molecule. NBU degrades upon exposure to mild UV irradiation. Therefore, this UV-degradable carrier allows us to control the chemical characteristics of the polymer/DNA complex (polyplex) particles at desired locations within the intracellular environment. By using this photolytic DNA carrier, we found that the exact timing of the UV degradation significantly influences the gene transfection efficiencies of ENE4-1/DNA(pGL2) polyplexes in HeLa cells. Interestingly, even if the polyplexes were UV-degraded at different intracellular locations/times, their nuclear entry efficiency was not influenced by the location/timing of UV degradation. The UV treatment did not influence the size or binding strength of the polyplexes. However, we confirmed that the degradation of the carrier molecules impacts the chemical characteristics of the polyplexes (it produces carbamic acid and nitrosobenzyl aldehyde groups on ENE4-1). We believe that these anionic acid groups enhance the interaction of the polyplexes with nuclear transcription proteins and thus the final gene expression levels; this effect was found to occur, even though UV irradiation itself has a general effect of reducing transfection efficiencies. Excess (uncomplexed) ENE4-1 polymers appear to not play any role in the UV-enhanced gene transcription phenomenon.

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Benzo-fused bicyclic imides

Cited by 30 publications

References 1 publication

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

Synthesis of Photocleavable Linear Macromonomers by ATRP and Star Macromonomers by a Tandem ATRP−Click Reaction: Precursors to Photodegradable Model Networks

A photo-degradable gene delivery system for enhanced nuclear gene transcription

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