Patent GB-1489412-A (GB)
Title: Furo(3,4-b)furan derivatives and their use in pharmaceutical compositions
IPC: C07C49/16
Filed: 1974-09-27
Abstract: 1489412 Furofurans IMPERIAL CHEMICAL INDUSTRIES Ltd 4 Sept 1975 [27 Sept 1974] 42040/74 Heading C2C [Also in Division A5] The invention comprises compounds of the formula  where R<SP>1</SP> is a hydrogen tom, an alkyl radical of from 1 to 10 carbon atoms or a phenyl radical; R<SP>2</SP> is a hydrogen atom or a phenyl radical; and wherein R<SP>3</SP> is a hydrogen atom or an alkyl radical of from 1 to 10 carbon atoms and R<SP>4</SP> is a hydrogen atom or an alkoxycarbonyl radical of from 2 to 10 carbon atoms; or, when R<SP>2</SP> is a hydrogen atom, R<SP>3</SP> is a hydrogen atom and R<SP>4</SP> is a radical of the formula R<SP>5</SP>SCH 2 -, wherein R<SP>5</SP> is a benzyl radical or a phenyl radical optionally bearing one or two substituents selected from halogen atoms, alkyl and alkoxy radicals each of from 1 to 4 carbon atoms, and carboxylic acid radicals; or R<SP>3</SP> and R<SP>4</SP> together form the methylene radical (= CH 2 ); but excluding such compounds wherein: (a) R<SP>1</SP> is an n-butyl radical, R<SP>2</SP> is a hydrogen atom, and either R<SP>3</SP> is a hydrogen atom and R<SP>4</SP> is a hydrogen atom or a methoxycarbonyl radical, or R<SP>3</SP> is a methyl radical and R<SP>4</SP> is a hydrogen atom, or R<SP>3</SP> and R<SP>4</SP> together form the methylene radical; (b) R<SP>1</SP> is an ethyl isopropyl or npentyl radical and R<SP>2</SP>, R<SP>3</SP> and R<SP>4</SP> are all hydrogen atoms; (c) R<SP>1</SP> is a methyl radical, R<SP>2</SP> is a phenyl radical, R<SP>3</SP> is a hydrogen atom or a methyl radical, and R<SP>4</SP> is a hydrogen atom; or (d) R<SP>1</SP> is a hydrogen atom or a phenyl radical, R<SP>2</SP> is a phenyl radical; and R<SP>3</SP> and R<SP>4</SP> are hydrogen atoms. The compounds may be prepared by a method which comprises (a) for a compound of Formula I wherein R<SP>4</SP> is an alkoxycarbonyl radical of from 2 to 10 carbon atoms, oxidizing the olefinic bond in a compound of the formula where R<SP>6</SP>, R<SP>7</SP> and R<SP>8</SP> are each alkyl of 1 to 9 carbon atoms and cyclizing the product thereby obtained by reaction with an acid; (b) for a compound of Formula I wherein R<SP>4</SP> is hydrogen, the stages of (i) hydrolysing the corresponding compound of Formula I wherein R<SP>4</SP> is an alkoxycarbonyl radical of from 2 to 10 carbon atoms and then (ii) decarboxylating the intermediate compound of Formula I obtained wherein R<SP>4</SP> is a carboxylic acid radical; (c) for a compound of Formula I wherein R<SP>3</SP> and R<SP>4</SP> together form the methylene radical, reacting a carboxylic acid of the formula with formaldehyde; (d) for a compound of Formula I wherein R<SP>3</SP> is a methyl radical and R<SP>4</SP> is a hydrogen atom, reducing the corresponding compound of Formula I wherein R<SP>3</SP> and R<SP>4</SP> together form the methylene radical; (e) for a compound of Formula I wherein R<SP>2</SP> and R<SP>3</SP> are hydrogen atoms and R<SP>4</SP> is a radical of the formula R<SP>5</SP>SCH 2 -, reacting the corresponding compound of Formula I wherein R<SP>3</SP> and R<SP>4</SP> together form the methylene radical, with a thiol of the formula R<SP>5</SP>-SH; (f) for a compound of Formula I wherein R<SP>2</SP>, R<SP>3</SP> and R<SP>4</SP> are each hydrogen atoms, cyclising a compound of the formula wherein R<SP>7</SP> is an alkyl radical of from 1 to 9 carbon atoms; (g) for a compound of Formula I wherein R<SP>3</SP> is an alkyl radical of from 1 to 10 carbon atoms and R<SP>4</SP> is an alkoxycarbonyl radical of from 2 to 10 carbon atoms, alkylating the corresponding compound of Formula I wherein R<SP>3</SP> is a hydrogen atom and R<SP>4</SP> is an alkoxycarbonyl radical of from 2 to 10 carbon atoms by reaction with an alkyl halide of the formula R<SP>9</SP>X, wherein R<SP>9</SP> is an alkyl radical of from 1 to 10 carbon atoms, and X is a displaceable radical; (h) for a compound of Formula I wherein R<SP>2</SP> is a phenyl radical, R<SP>3</SP> is a hydrogen atom or an alkyl radical of 1 to 10 carbon atoms and R<SP>4</SP> is a hydrogen atom or an alkoxycarbonyl radical of from 2 to 10 carbon atoms, reacting a succinic anhydride derivative of the formula with a compound of the formula The invention further comprises racemic compounds of Formula I wherein R<SP>1</SP> is an n-butyl radical, R<SP>2</SP> and R<SP>4</SP> are hydrogen and R<SP>3</SP> is a methyl radical. These compounds are prepared by hydrolysing and decarboxylating the corresponding racemic compound of the formula or by reducing racemic canadensolide or 6-epicanadensolide in the presence of a palladium catalyst.