Edward Walton

Synthesis of 9-(3-deoxy-3-C-methyl-β-d-xylofuranosyl)-adenine: a branched-chain sugar analog of cordycepin

Abstract Reaction of methyl 2,3-anhydro-5- O -trityl-β- d -ribofuranoside ( 4 ) with methyl-magnesium chloride gave a mixture of methyl 3-chloro-3-deoxy-5- O -trityl-β- d -xylofuranoside ( 5 ) and methyl 3-deoxy-3- C -methyl-5- O -trityl-α- d -xylofuranoside ( 6 ). Removal of the trityl group from 6 gave methyl 3-deoxy-3- C -methyl-β- d -xylofuranoside ( 9 ), which, on treatment with p -nitrobenzoyl chloride, gave methyl 3-deoxy-3- C -methyl-2,5-di- O -( p -nitrobenzoyl)-β- d -xylofuranoside ( 10 ). The glycosyl chloride ( 15 ) derived from 10 reacted with 6-(benzamido)chloromercuripurine to give 6-(benzamido)-9-[3-deoxy-3- C -methyl-2,5-di- O -( p -nitrobenzoyl)- d -xylofuranosyl]purine ( 16 ). Alkaline methanolysis of 16 produced 9-(3-deoxy-3- C -methyl-α- d -xylofuranosyl)-adenine (α- 1 ) and 9-(3-deoxy-3- C -methyl-β- d -xylofuranosyl)adenine (β- 1 ) in the ratio of 1:4. Treatment of 6 with benzoyl chloride gave methyl 2- O -benzoyl-3-deoxy-3- C -methyl-5- O -trityl-β- d -xylofuranoside ( 17 ). The trityl group was removed from 17 to give methyl 2- O -benzoyl-3-deoxy-3- C -methyl-β- d -xylofuranoside ( 18 ), which was converted into methyl 2,5-di- O -benzoyl-3-deoxy-3- C -methyl-β- d -xylofuranoside ( 19 ). When the glycosyl halide ( 20 ) obtained from 19 reacted with 6-(benzamido)chloromercuripurine, 6-(benzamido)-9-(2,5-di- O -benzoyl-3-deoxy-3- C -methyl- d -xylofuranosyl)-purine ( 21 ) was produced. Ammonolysis of 21 gave α- 1 and β- 1 in the ratio of 1:16.