ChemInform Abstract: SYNTHESIS AND BIOLOGICAL PROPERTIES OF BENZOFURAN ANALOGS OF ASPIRIN

Royer, R.; Risse, S.; Demerseman, P.; Albert, Odile; Nicoine, F.

doi:10.1002/chin.197942216

Cited by 2 publications

(2 citation statements)

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“…A suspension of benzyltriphenylphosphonium bromide (1.85 g, 4.26 mmol) in THF (30 mL) was treated with a solution of lithium bis(trimethylsilyl)amide (4 mL of a 1 M solution in THF, 3.98 mmol). The reaction mixture was stirred at room temperature for 30 min, and then a solution of 5-methoxy-1-benzofuran-2-carbaldehyde (0.50 g, 2.84 mmol) in THF (10 mL) was added. After 20 min water was added and the THF was removed at reduced pressure.…”

Section: Methodsmentioning

confidence: 99%

4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

et al. 2006

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High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

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Section: Methodsmentioning

confidence: 99%

4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

et al. 2006

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“…As expected, the total demethylation occured for 1q, whereas 1n-p led to a mixture of partially and totally demethylated products. The main products obtained from 1n-p were 7-, 6-or 5-hydroxy-2-methylbenzo [b]furans 6n-p [6][7][8] respectively in about 20% yield (Scheme 4). In an attempt to obtain the completely demethylated phenylnaphthalenes 3n-p, 1n-p were treated with an excess of boron tribromide (10 equiv) under reflux overnight.…”

mentioning

confidence: 99%

The Reaction of Arylacetones with Boron Tribromide

Dupont¹,

Cotelle²

1999

Synthesis

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Treatment of arylacetones 1 with boron tribromide gives 1,3-dimethyl-2-arylnaphthalenes 3 in fair to good yields by a tandem aldol condensation-intramolecular cyclization. This reaction is limited to the electron-rich arylacetones. In the case of methoxyphenylacetones, a demethylation occurs leading to 1,3-dimethyl-2-hydroxyphenylnaphthols. Other cyclization may occur for orthomethoxyphenylacetones leading to intramolecular acetal 4b or 5-, 6-or 7-hydroxy-2-methylbenzo[b]furans 6n-p. In the case of the 1-naphthylacetone, a bromination reaction of the phenanthrene 3i occurs leading to bromophenanthrene 5i.Highly substituted phenylnaphthalenes are common features of numerous biologically significant products and pharmaceuticals 1 and new or improved methods for their regioselective construction have received significant attention in recent years. 2 The most important reported routes to 2-phenylnaphthalenes include the following: (i) Suzuki coupling 3 of the appropriate 2-naphthylboronic acid with iodobenzenes; (ii) Stille coupling 3 of trifluoromethylsulfonyloxynaphthalene for example with arylstannates; (iii) Katritzky annulation. 2g As a part of our studies on the synthesis of new biologically active polyhydroxylated compounds, we have developed a new convenient synthesis of polyhydroxylated 2-phenylnaphthalenes in a one pot procedure from mono-or dimethoxyphenylacetones and boron tribromide. 4 The extension of this reaction to arylethanals has revealed remarkable aspects of product differentiation, 5 i.e., formation of 2-phenylnaphthalene from phenylethanal and epoxydibenzo[a,e]cyclooctenes from activated arylethanals.We now report the generalization of the reaction of arylacetones with boron tribromide in order to clearly define the scope and the limitation of this reaction.When the aromatic ring was unsubstituted or substituted by an electron-donating group (OCH 3 , CH 3 , F) 1,3-dimethyl-2-arylnaphthalenes 3 were obtained in moderate to high yields (Scheme 1 , Tables 1 and 2, compounds 1a-i). Boron tribromide reacted with phenylacetone to give a boron enolate which reacted stereoselectively with another molecule of phenylacetone to give the aldol condensation product 2. Compound 2 underwent an intramolecular reaction to give 3. As expected methyl or methoxyphenylacetones (1b-d, 1h) gave 3 in high yields whereas fluorophenylacetones (1e-g) gave 3 in lower yields probably due to the deactivating effect of the fluorine atom. 3-Fluorophenylacetone 1f gave the best yield of this series due to para orientation of the fluorine atom in the cyclization.The intramolecular reaction was also highly regioselective as attested by the formation of only one product from 1c and 1f. Nevertheless, byproducts might be obtained in the cases of 1b and 1i; the former compound gave an intramolecular acetal 4b (Scheme 2) and the latter a brominated phenanthrene 5i (Scheme 3). Since phenanthrene treated with boron tribromide was totally recovered, we supposed that the bromination is due to the activating effect of the methyl and the n...

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ChemInform Abstract: SYNTHESIS AND BIOLOGICAL PROPERTIES OF BENZOFURAN ANALOGS OF ASPIRIN

Cited by 2 publications

References 0 publications

4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

The Reaction of Arylacetones with Boron Tribromide

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