Benzofurancarboxylic acids

Treatment of 3-(2-furylmethylene)-5-aryl-2(3//)-furanones (38) with A1C13 in benzene led to alkyl-oxygen ring cleavage to give resonance stabilized carbocations 39, which upon electrophilic attack in the ortho position yield the corresponding benzofurancarboxylic acids (40) (Scheme 12) (77JPR689). 

Coumestans,21 although they have a fused benzofuran ring, will be surveyed as being 8-lactones of 2-(2-hydroxyphenyl)-3-benzofuran carboxylic acids [coumestrol (4)22 is the 8-lactone of 2-(2,4-dihydroxy-phenyl)-6-hydroxy-3-benzofurancarboxylic acid]. The synthesis of some rotenoids 23 from benzofuran derivatives will also be reviewed, but dibenzofuran derivatives, such as usnic acid and its derivatives, will not be treated. 

Since the discovery of sodium chromoglycate (DSCG), a drug which is useful in the treatment of human asthma, several isosteric or structurally related bisbenzofuran systems have been synthesized. A recent example is 6,6 -[(2-hydroxypropane-l,3-diyl)bis(oxy)]-bis-(3-hydroxy-2-benzofurancarboxylic acid) diethyl ester trisodium salt trihydrate (510) (80JHC1U7). 

BENZOFURANCARBOXYLIC ACID, 4-BROMO-6-((DIMETHYLAMIN0)METHYL)-5-HYDROXY-, ETHYL ESTER HYDROCHLORIDE... 

BENZOFURANCARBOXYLIC ACID, 6-CHLORO-4-(DIMETHYLAMINOMETHYL)-5-HYDROXY-2-METHYL-, ETHYLESTER... 

BENZOFURANCARBOXYLIC ACID, 6-BROMO-5-HYDROXY-2-METHYL-4-((4-METHYL-... 

BENZOFURANCARBOXYLIC ACID, 2-((DIMETHYLAMINO)METHYL)-5-METHOXY-, ETHYL ESTER, HYDROCHLORIDE... 

Sodium hydrogen carbonate Thionyl chloride Copper iodide Diazomethane Imidazole Trifluoroacetic acid Sodium methoxide 7-Bromo-3a,8b-cis-3a,8b-dihydro-3H-5-cyclopenta[b] benzofurancarboxylic acid... 

Coumctrilic Acid or 2-Benzofurancarboxylic Acid [called CumarrisSure or Cumaron-carbonsaure -... 

Coumestrol, 5,9-Dihydroxy-6H-benzofuro[3w2-cJ-[l]benzopyran-6-one 2 (2r4 dihydroxyphenytb6-hydroxy-3 benzofurancarboxylic acid 6 -lactone V, 6 -di hydroxy couma -rino(3 4 3y2)coumarone. C 5H8Os mol wt 268,21, C 6717%, H 3.01%, O 29.83%. An estrogenic factor occurring... 

Dichloro-2,3-dihydro-5-(2-thienyl carbonyl)-2-benzofurancarboxylic acid... 

In the case of the related compound 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)-2-benzofurancarboxylic acid (Fig. 10), the diuretic and uricosuric properties are essentially completely separated. The (+)-5 -enan-tiomer, possessing the natriuretic activity, is twice as active as the racemate, with the uricosuric activity residing in the (—)-i -enantiomer [75,76]. It was postulated that a mixture of the two enantiomers could be prepared to yield an appropriate balance between the two actions [76]. Examination of nonracemic mixtures of the individual enantiomers in the chimpanzee resulted in the conclusion that the racemate possesses the optimal therapeutic ratio of the diuretic and uricosuric properties [75]. However, compared to humans the chimpanzee is a hyperresponder to uricosuric compounds and thus it may not be possible to extend this observation to man. A similar differentiation in enantiomeric activity has also been observed for the related compound 5-dimethylsulphamyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acid (DBCA) (Fig. 10), the uricosuric and diuretic activities being associated with the (+)-7 - and (—)-5-enantiomers, respectively [77]. 

Nakano, M. Kawahara, S. Stereoselective renal tubular secretion of a new uricosuric diuretic, 6,7-dichloro-5-(N,N-dimethylsulfamoyl)-2,3-dihydro-2-benzofurancarboxylic acid (5-8666) in C5momolgus monkeys. Xenobiotica 1992, 20, 179-185. 

Carboxyetheny [)-2-(3,4-dihy dr oxyphenyl)- -hydroxy-3-benzofurancarboxylic acid... 

Carboxydinorleukotriene E4, see A-10058 18-Carboxy-19,20-dinor LTB, see D-10205 5-(2-Carboxyethenyl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-3-benzofurancarboxylic acid, see S-30028... 

Dihydro-2-methyl-7-benzofurancarboxylic acid Me ester, in D-30122 1 -(2,5-Dihydroxyphenyl)-3-methyl-2-buten-1 -one, D-30240... 

Demethoxycapillarisin, in T-20161 2-(2,4-Dihydroxyphenyl)-6-hydroxy-3-benzofurancarboxylic acid, D-30238 7-Hydroxyaloeemodin, T-30177... 

Dihydroxyphenyl)-6-hydroxy-3-benzofurancarboxylic acid 2, 6-Di-Me ether. Me ester, in D-30238 2-(Ethoxymethyl)-1,3-dihydroxy-5-methoxyanthraquinone, w T-10152... 

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