GB1414841A - 2,5-anhydro-dalloses derivatives thereof and c-glycosylnucleosides derived therefrom - Google Patents

Abstract

1414841 2,5-anhydro-D-alloses and their nucleosides SYNTEX (USA) Inc 6 Feb 1973 [11 Feb 1972] 5858/73 Heading C2C Novel compounds I in which OR<SP>3</SP> is a hydrolyazble C 1-12 acyloxy group, t-butoxy, tetrahydropyran-2<SP>1</SP>-yloxy, 4<SP>1</SP>- methoxytetrahydropyran-2<SP>1</SP>-yloxy, benzyloxy (optionally substituted by nitro, halo, C 1-6 alkyl or C 1-6 alkoxy) and OR<SP>1</SP> and OR<SP>2</SP> are the same and are selected from the groups for OR<SP>3</SP> or together form an alkylenedioxy or cycloalkylidenedioxy group of up to 10 C atoms and R is phenyl optionally substituted by nitro, halo, C 1-6 alkyl or C 1-6 alkoxy are prepared from compound A in which R 9 is benzoyl (optionally substituted). Compound A is heated with dry halogen bromide in benzene and the product formed reacted with mercuric cyanide is nitromethane, to form a compound B in which R 10 is benzoyl. The free hydroxy (R 10 =H) compound is formed by reaction with sodium methoxide and neutralization. This is treated with isobutylene in concentrated sulphuric acid, or with dehydropyran or 4-methoxy 5,6-dihydro-2H-pyran in the presence of toluenesulphonic acid to yield the respective ether groups (R 10 =t-butyl, tetrahydropyran-2-yl or 4-methoxy-tetrahydropyran-4-yl). Compounds B are reacted with sodium hypophosphite and Raney nickel in pyridine/water/acetic acid and with an N,N<SP>1</SP>-diphenylethylenediamine to form a compound I in which R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> are benzoyl, butyl or the above pyranyl groups. Compounds I (R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>=benzoyl) are hydrolysed and treated with (a) sodium hydride in dimethyl sulphoxide followed by benzyl chloride to form compounds I in which R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> are benzyl or (b) a carboxylic acid anhydride in pyridene to form compounds I in which R<SP>1</SP> R<SP>2</SP> and R<SP>3</SP> are acyl. Treatment of compounds I (R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>= benzoyl) with methanolic ammonia gives the 2,3- dehydroxy compound which is reacted with a ketone and the corresponding acetal in the presence of perchloric acid to yield compounds I in which R 2 and R 3 are alkylidene or cycloalkylidene. Novel compounds III in which R<SP>4</SP> is 3(5)-carboxy-4-pyrazolyl, 3,5- dicarboxy-4-pyrazolyl, 5-carboxy-3-isoxazolyl, 4,5-dicarboxy-3-isoxazolyl or a hydrolysable ester containing up to 12 C atoms or the amide thereof, OR<SP>7</SP> is hydroxy, C 1-12 hydrolysable acyloxy group, t-butoxy tetrahydropyran-2- yloxy, 4-methoxytetrahydropyran-4-yloxy benzyloxy (optionally substituted by nitro, halo, C 1-6 alkyl or C 1-6 alkoxy) and OR<SP>5</SP> and OR<SP>6</SP> are the same and are selected from the groups OR<SP>7</SP> or are together alkylidene or cycloalkylidene of up to 10C atoms are obtained from compounds I Thus Compound VIII is prepared by reacting a novel Compound II (prepared from Compounds I by method claimed in 50993/74 (Specification 1,414,842) with carbomethoxymethylene triphenyl phosphorane to form a compound IV which upon reaction with diazomethane yields the corresponding 2-pyrazoline which is halogenated and dehydrohalogenated with chlorine in CCl 4 to yield a Compound V which yields the methyl ester of Compound VIII by one of the following treatments: (1) when OR<SP>1</SP>, OR<SP>2</SP> and OR<SP>3</SP> are ester groups with a sodium methoxide and a cation exchange resin in hydrogen form (2) when OR<SP>1</SP>, OR<SP>2</SP> and OR<SP>3</SP> are benzyloxy, with ethanol containing 10% of (10% Pd on BaSO 4 ) and hydrogen with vigorous stirring, (3) when OR<SP>1</SP>, OR<SP>2</SP> and OR<SP>3</SP> are the remaining groups with 90% trifluoroacetic acid at room temperature. Treatment of compound (V) or the methyl ester of compound VIII with methanolic ammonia yields the amide of compound VIII. Treatment of the methyl ester with sodium hydroxide gives the free carboxylic acid VIII. Compounds (IX) in which R 12 is carboxy, a C 1-12 acyloxy group or carboxamido are prepared by reacting compounds IV with ethyl diazoacetate to yield a 2-pyrazolidine which undergo a similar set of reactions as above to yield compounds IX. Compounds XIII and XV in which R 13 and R 14 are carboxy. C 1-12 acyloxy or carboxamido are prepared by reacting aldehyde II with hydroxylamine hydrochloride and the resulting oxime is chlorinated in a diethyl ether solution to give an oximino chloride which upon reaction with (a) ethyl propiolate in the presence of triethylamine gives a 5-carbethoxy-3-isoxazole derivative or with (b) dimethylacetylene dicarboxylate in the presence of triethylamine forms the 4,5-dicarbmethoxy-3- isoxazole derivative. These derivatives undergo reactions as described above to yield the various compounds XIII and XIV. Compounds III are anti-metabolic, antibacterial and anti-viral agents and form with an excipient a pharmaceutical composition.