Syntheses of 3-acetoacetylaminobenzo[b]furan derivatives having cysteinyl leukotriene 2 receptor antagonistic activity

Novel 3-acetoacetylaminobenzo[b]furan derivatives having a modified triene system at the 3-position were synthesized starting with 3-aminobenzo[b]furans. The enol isomers, 3-[(3-hydroxybut-2-enonyl)amino]benzo[b]furans (), of the 3-acetoacetylaminobenzo[b]furans were obtained as stable isomers owing to formation of a hydrogen bonding between the enol hydroxyl group and the amidocarbonyl group. The planarity of the C-2 substituent through the C-3 side chain suggested the existence of a modified conjugational triene system in the enol compound. Cysteinyl leukotriene 1 and 2 receptor antagonistic activities for these compounds were evaluated. 2-(4-Cyanobenzoyl or ethoxycarbonyl)-3-[(2-cyano-3-hydroxybut-2-enonyl)amino]benzo[b]furans (, ) were moderately active.     

Preparation of 2-, 3-, 4- and 7-(2-alkylcarbamoyl-1-alkylvinyl)benzo[b]furans and their BLT1 and/or BLT2 inhibitory activities

Several 2-alkylcarbamoyl-1-alkylvinylbenzo[b]furans were designed to find a selective leukotriene B4 (LTB4) receptor antagonist. 2-(2-Alkylcarbamoyl-1-alkylvinyl)benzo[b]furans having a substituent group at the 3-position, 4-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans having a substituent group at the 3-position, and 7-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans and 3-(2-alkylcarbamoyl-1-alkylvinyl)benzo[b]furans were prepared and evaluated for LTB4 receptor (BLT1 and BLT2) inhibitory activities. (E)-3-Amino-4-[2-[2-(3,4-dimethoxyphenyl)ethylcarbamoyl]-1-methylvinyl]benzo[b]furan ((E)-17c) showed potent and selective inhibitory activity for BLT2. On the other hand, (E)-7-(2-diethylcarbamoyl-1-methylvinyl)benzo[b]furan ((E)-27a) showed potent inhibitory activity for both BLT1 and BLT2.     

Synthesis and biological activities of novel furo[2,3,4-jk][2]benzazepin-4(3H)-one derivatives

A novel seven-membered lactam formation method has been established by intramolecular ring closure reaction of 4-bromo-(E)-3-[(2-alkylvinyl)carbonylamino]benzo[b]furans under Heck coupling conditions. A number of furo[2,3,4-jk][2]benzazepin-4(3H)-ones, tricyclicbenzo[b]furans, have been prepared by this method and evaluated for their leukotriene B(4) (LTB(4)) receptor and poly(ADP-ribose)polymerase-1 (PARP-1) inhibitory activities.     

Regioselective preparation of benzo[b]furans from phenols and α-bromoketones

In this paper, a fully regiocontrolled synthesis of either 2- and 3-substituted benzo[b]furans is described. Direct reaction between phenols and α-bromoacetophenones in the presence of neutral alumina yields 2-substituted benzo[b]furans with complete regiocontrol. When a basic salt such as potassium carbonate is used, the corresponding 2-oxoether is obtained. Cyclization of these latter compounds promoted by neutral alumina yields the corresponding 3-substituted benzo[b]furans. Using the former method, Moracin M and other analogues can be obtained from commercial sources in two preparative steps. DFT calculations provide reasonable reaction paths to understand the formation of 2-substituted benzo[b]furans.     

Synthesis and reactions of benzo[b]furo[2,3-c]pyrylium salts

A method has been developed for the synthesis of 3-acetonyl- and 3-phenacylben-zo[b]furans by cyclization of 1-arloxy-2,4-pentanediones and 1-phenyl-4-aryloxy-1,3-butanediones in polyphosphoric acid. Acylation of 3-acetonyl(phenyl-benzo-[b]furans with aliphatic acid anhydrides in the presence of perchloric acid gives the benzo[b]furo[2,3-c]pyrylium perchlorates. The recyclization of the pyrylium salts with ammonia, aqueous alkali, and morpholine has been examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 889–893, July, 1987.     

Iodine(III)-Mediated Tandem Oxidative Cyclization for Construction of 2-Nitrobenzo[b]furans

Various 3-alkyl-2-nitrobenzo[b]furans were synthesized from common intermediate 2-(2-nitroethyl)phenols via a hypervalent iodine-induced oxidative cyclization, with good to excellent yields. This facile route is able to efficiently functionalize 2-nitrobenzo[b]furans, which are difficult to obtain by classical methods.     

Novel and selective palladium-catalyzed annulations of 2-alkynylphenols to form 2-substituted 3-halobenzo[b]furans

[reaction: see text] A novel and selective palladium-catalyzed annulation of 2-alkynylphenols method for the synthesis of 2-substituted 3-halobenzo[b]furans is presented. In the presence of PdX(2), CuX(2), and HEt(3)NX, 2-substituted 3-halobenzo[b]furans were selectively obtained as the major products. The mechanism of the reaction was also discussed.     

Parallel synthesis of a multi-substituted benzo[b]furan library

The solution-phase parallel synthesis of a 121-member library of multi-substituted benzo[ b]furans is described. 2,3,5-Trisubstituted benzo[ b]furans have been prepared by the palladium-catalyzed substitution of 3-iodobenzofurans by Suzuki-Miyaura, carbonylative Suzuki, Sonogashira, Heck, and carboalkoxylation chemistry. The 3-iodobenzofurans are readily prepared in good to excellent yields by the palladium/copper-catalyzed cross-coupling of various o-iodoanisoles and terminal alkynes, followed by electrophilic cyclization with ICl.     

Synthesis of 2-arylbenzo[b]furans via copper(I)-catalyzed coupling of o-iodophenols and aryl acetylenes

[reaction: see text] We report a copper(I)-catalyzed procedure for the synthesis of 2-arylbenzo[b]furans. This protocol can be used to synthesize a variety of 2-arylbenzo[b]furans in good to excellent yields. This method can tolerate a variety of functional groups, does not require the use of expensive additives, and is palladium-free.     

Sequential and one-pot reactions of phenols with bromoalkynes for the synthesis of (Z)-2-bromovinyl phenyl ethers and benzo[b]furans

Benzo[b]furans were prepared in one pot based on the addition/palladium-catalyzed C-H bond functionalization of phenols with bromoalkynes. The addition reactions of phenols to bromoalkynes generated (Z)-2-bromovinyl phenyl ethers in high yields with excellent regio- and stereoselectivity. The obtained (Z)-2-bromovinyl phenyl ethers subsequently proceeded by intramolecular cyclization to afford 2-substituted benzo[b]furans in good yields through palladium-catalyzed direct C-H bond functionalizations. It is important to note that the transformation of phenols with bromoalkynes into benzo[b]furans could be carried out in one pot with a simple and efficient tandem procedure.     

A multi-component coupling approach to benzo[b]furans and indoles

A single step access to multiply substituted benzo[b]furans and indoles has been developed.     

Preparation of 3-acetoacetylaminobenzo[b]furan derivatives with cysteinyl leukotriene receptor 2 antagonistic activity

Novel 3-acetoacetylaminobenzo[b]furan derivatives with a modified triene system at the 3-position were prepared through acylation of the 3-aminobenzo[b]furans with 5-methylisoxazole-4-carboxylic acid chloride followed by basic cleavage of the isoxazole ring and several of these compounds showed moderate cysteinyl leukotriene receptor 2 antagonistic activity.     

A new and efficient synthesis of 4-functionalized benzo[b]furans from 2,3-dihalophenols

Tandem Sonogashira coupling/5-endo-dig cyclization reactions on 2,3-dihalophenols suppose a straightforward entry to 4-halobenzo[b]furans, which can be easily transformed into 4-functionalized benzo[b]furans, that are difficult to synthesize by other procedures. On the other hand, the starting 2,3-dihalophenols are efficiently prepared from commercially available 3-halophenols, via their N,N-diethyl carbamates by selective lithiation at the 2-positions by treatment with s-BuLi/TMEDA or LDA at low temperature and reaction with halogen electrophilic reagents.     

2-芳基苯并[b]呋喃衍生物的生物活性与合成策略

2-芳基苯并呋喃是一类广泛存在于植物中的化合物,具有良好的抗病毒、抗肿瘤、抗真菌、抗氧化等生物活性,一直以来都引起人们的广泛关注.综述了近年来2-芳基苯并呋喃类化合物的研究进展,重点介绍其生物活性和合成方法,尤其是苯并呋喃环的构建方法.     

Palladium-catalyzed carbonylative annulation of o-alkynylphenols: syntheses of 2-substituted-3-aroyl-benzo[b]furans

We report here a general synthetic methodology for palladium-catalyzed carbonylative annulation of o-alkynylphenol to construct 2-substituted-3-aroyl-benzo[b]furan. On the basis of the results, this methodology could be applied to a wider selection of iodide substrates to generate desired products. In accordance with mechanistic studies, this process involves coordination of cationic and less hindered acyl palladium complexes with o-alkynylphenols to create a desired cascade triad (coordination, nucleophilic addition, and reductive elimination). Consistent with this mechanism, addition of 1 equiv of AgBF(4) to palladium catalyst Pd(Ph(3)P)(4) generates an ideal candidate for this unique transformation.     

Synthesis of 2-aminofurans and 2-unsubstituted furans via carbenoid-mediated [3 + 2] cycloaddition

An efficient dual synthetic manifold for 2-aminofurans and 2-unsubstituted furans has been developed. The carbenoid-mediated [3 + 2] cycloaddition of copper carbenoids with enamines provides 2-amino-2,3-dihydrofurans which serve as common intermediates for both 2-aminofurans and 2-unsubstituted furans.     

New synthesis of 2-aryl-3-substituted benzo[b]furans from benzyl 2-halophenyl ethers

Treatment of benzyl 2-halophenyl ethers with 3 equiv of t-BuLi results in Li-halogen exchange and lithiation at benzylic methylene simultaneously. These dianions do not undergo Wittig rearrangement and can be trapped with electrophiles. Their reactions with carboxylic esters afford the corresponding 2-aryl-3-hydroxy-2,3-dihydrobenzo[b]furans as a mixture of diastereoisomers. Subsequent acid-catalyzed or mediated dehydration gives moderate to good overall yield of a variety of 2-aryl-3-substituted benzo[b]furans.     

Convenient One‐Pot Protocol for an Exclusive Synthesis of 4‐Cyano/ethoxycarbonyl‐2,2‐dimethyl‐2H‐chromene and/or 3‐Cyano/ethoxycarbonyl‐2‐isopropyl‐benzo[b]furan from a Single Oxo‐ylide

[{2‐(Fluoroaryloxy)‐2‐methyl‐propanoyl}‐(cyano/ethoxycarbonyl) methylene]triphenylphosphoranes underwent microwave‐assisted tandem intramolecular Wittig and Claisen rearrangement and internal cyclization reactions to afford fluoro‐substituted 2,2‐dimethyl‐2H‐chromenes and/or 2‐isopropyl‐benzo[b]furans in good yield. Upon controlled microwave irradiation in the presence of Nafion H catalyst in xylene, the oxo‐ylides selectively formed 4‐cyano/ethoxycarbonyl‐2,2‐dimethyl‐2H‐chromenes. Microwave irradiation of the same oxo‐ylide in the presence of K₂CO₃ as catalyst or in a polar solvent–like sulfolane resulted in the exclusive formation of the corresponding fluoro‐substituted 3‐cyano/ethoxycarbonyl‐2‐isopropyl‐benzo[b]furans.     

Synthesis of 3-Methylthio-benzo[b]furans/Thiophenes via Intramolecular Cyclization of 2-Alkynylanisoles/Sulfides Mediated by DMSO/DMSO-d6 and SOCl2

The reaction of 2-alkynylanisoles/sulfides with SOCl2 and DMSO was conducted to conveniently furnish the biologically interesting 3-(methylthio)-benzo[b]furans/...     

Indolobenzofurans. 1. Synthesis of isomeric indolobenzo[b]furans

The synthesis of four progenitors of a new tetracyclic condensed system of indolobenzo [b]furans on the basis of the Fischer reaction has been described. It has been shown that the cyclization of 2-dibenzofuranyl- and 3-dibenzofuranylhydrazones of ethyl pyruvate in ethyl polyphosphate results in the simultaneous formation of the corresponding cyclic ethers with both angular and linear structures.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1366–1370, October, 1984.