Préparation et couplage sur des polypeptides de 5′- O-carboxyméthyl-ribonucléosides

Abstract

Condensation of ethyl iodoacetate with the sodium salt of methyl 2,3- O-isopropylidene-α,β- d-ribofuranoside gave the ester 1 which was reduced with lithium aluminium hydride to methyl 5- O-(2-hydroxyethyl)-2,3- O-isopropylidene-α,β- d-ribofuranoside ( 3). Removal of the protecting group gave a substituted ribose derivative which was either peracetylated, or used for the synthesis of 5′- O-(2-hydroxyethyl)-adenosine ( 16), or glycosidated to give 5- O-(2-hydroxyethyl)- d-ribofuranoside ( 5). The tribenzoate of 5 was converted into 1- O-acetyl-2,3-di- O-benzoyl-5- O-(2-benzoyloxyethyl)- d-ribofuranose ( 6), which gave a glycosyl halide used for the syntheses of the 5′- O-(2-hydroxyethyl) derivatives of uridine ( 9), cytosine ( 12), and guanosine ( 14). These four substituted ribonucleotides were catalytically oxidized to give the 5′- O-carboxymethylnucleotides 10, 13, 15, and 17, which were condensed with polyalanine-polylysine in the presence of carbodiimides to give potential antigens. The synthesis of 2′3′- O-benzylidene-5′- O-carboxymethyluridine is also described.