Patent GB-778106-A (GB)
Title: Improvements relating to ribofuranosylpurines which are new organic compounds, and the preparation thereof
IPC: C07H19/16
Filed: 1955-04-28
Abstract: The invention comprises compounds of the formula: <FORM:0778106/IV(b)/1> where R1 and R5 are hydrogen or methylmercapto radicals, and R2, R3 and R4 are hydrogen or acetyl or benzoyl radicals.  Such compounds are obtained by condensing a chloromercury salt of a 6-dimethylaminopurine or a methylmercapto derivative thereof with a 1-halo - 2,4,5 - triacetyl or tribenzoyl - D - ribofuranose and if desired deacylating and/or reremoving by hydrogenolysis the methylmercapto group or groups from the condensation product. The chloromercury salt may be employed in the form of a suspension on diatomaceous earth.  When methylmercapto groups are present at both the 2- and 8-positions of the purine the condensation product is a mixture which contains also a 6-dimethylamino-7-(triacryl - b  - D - ribofuranosyl) - purine, the mixture, after removal of acyl and methylmercapto groups, being separated into 7- and 9-isomers by chromatography or fractional crystallization.  Although deacylation and removal of methylmercapto groups may be effected in either order, it is preferred to remove the methylmercapto groups first.  This may be done by refluxing the condensation product with Raney nickel catalyst in the presence of a neutral non-halogenated solvent. The acyl groups can be removed by transesterification by heating with an alkali metal alkoxide or alkaline earth metal alkoxide in the presence of an alkanol containing 1 to 6 carbon atoms.  In examples: (1) and (2) triacetyl - D - ribofuranosyl chloride (from the reaction of D-ribofuranose tetra-acetate with ethereal hydrogen chloride) is reacted in xylene with 2 - methylmercapto - 6 - dimethylaminopurine mercuric chloride on diatomaceous earth to give 2 - methylmercapto - 6 - dimethylamino - 9 - (21,31,51 - triacetyl - b  - D - ribofuranosyl)purine; (3) tribenzoyl - D - ribofuranoxyl chloride (obtained by the reaction of 1 - acetyl - 2,3,5 - tribenzoyl - b  - D - ribofuranose) is reacted in benzene and xylene with 2 - methylmercapto - 6 - dimethylaminopurine mercuric chloride suspended on diatomaceous earth to give 2 - methylmercapto - 6 - dimethylamino - 9 - (21,31,51 - tribenzoyl - b  - D - ribofuranosyl)purine; (4) and (5) the products of Examples (1) and (2) are treated with Raney nickel in methanol to give 6-dimethylamino-9-(21,31,51 - triacetyl - b  - D - ribofuranosyl) purine, from which the picrate is prepared; (6) 2-methylmercapto - 6 - dimethylamino - 9 - (21, 31,51 - tribenzoyl - b  - D - ribofuranosyl)purine is treated with Raney nickel to give 6-dimethylamino - 9 - (21,31,51 - tribenzoyl - b  - D - ribofuranosyl)purine; (7) triacetyl - D - ribofuranosyl chloride is reacted with 6-dimethylaminopurine mercuric chloride to give 6-dimethylamino - 9 - (21,31,51 - triacetyl - b  - D ribofuranosyl)purine; (8) tribenzoyl-D-ribofuranosyl chloride is reacted in benzene and xylene with 6-dimethylaminopurine mercuric chloride on diatomaceous earth to give 6-dimethylamino - 9 - (21,31,51 - tribenzoyl - b  - -ribofuranosyl)purine; (9) the product of Example (3) is heated with methanol and sodium methoxide to give 2-methylmercapto-6-dimethylamino - 9 - b  - D - ribofuranosylpurine; (10) to (14) 6-dimethylamino-9-b -D-ribofuranosylpurine is prepared by refluxing the products of Examples (4) to (8) with anhydrous methanol and sodium methoxide; (15) 2-methylmercapto - 6 - dimethylamino - 9 - b  - D - ribofuranosylpurine is treated with Raney nickel to form 6-dimethylamino-9-b -D-ribofuranosylpurine; (16) tribenzoyl-D-ribofuranosyl chloride is reacted with 2,8-bis-methylmercapto-6-dimethylaminopurine mercuric chloride on diatomaceous earth to give a mixture of 2,8-bismethylmercapto - 6 - dimethylamino - 7-(21,31,51 - tribenzoyl - b  - D ribofuranosyl)purine and 2,8 - bis - methylmercapto - 6 - dimethylamino - 9 - (21,31,51 - tribenzoyl - b  - D - ribofuranosyl)purine; (17) the mixed product of Example (16) is treated with Raney nickel to give a mixture of 6 - dimethylamino - 7-(21,31,51 - tribenzoyl - b  - D - ribofuranosyl)purine and 6 - dimethylamino - 9 - (21,31,51 - tribenzoyl-b  - D - ribofuranosyl)purine; (18) the mixture obtained in Example (1) is refluxed with methanol and sodium methoxide, and the product obtained is separated by partial extraction with ethyl acetate into 6-dimethylamino-7-b -D-ribofuranosylpurine and 6-dimethylamino-9-b -D-ribofuranosylpurine.  The separation may alternatively be effected (Example (I9)) by chromatography on diatomaceous earth using water saturated with ethyl acetate as solvent.