摘要 |
2'-Substituted-D-ribofuranosyl purine compounds, especially 2'-azido-D-ribofuranosyl purine compounds, of the formula <IMAGE> (I) in which R1 is azide, amino, halogen or alkoxy, and R2 is the residue of a purine base and particularly a 9-adenyl group, a 7-guanyl group, or a 9-guanyl group (the waved lines in formula I above show that R2 can be bound in the alpha - or beta -configuration), ARE PREPARED BY A PROCESS COMPRISING (A) REACTING A URIDINE DERIVATIVE WITH AN ALKALI AZIDE (WHEN R1 is to be azide or, through further conversion, an amine group) or a halide (when R1 is halogen) or with an alkylating agent (when R1 is alkoxy); (B) TRANSFORMING THE RESULTING COMPOUND WITH HYDRAZINE INTO THE CORRESPONDING 2-DEOXY-RIBOSE; (C) CONVERTING THE 2-DEOXY-RIBOSE INTO A 1-O-methylglucoside with methanol in the presence of a strong acid; (D) REACTING THE GLUCOSIDE WITH ACETIC ANHYDRIDE IN A POLAR ORGANIC SOLVENT TO FORM A 1-O-methyl-ribose-3,5-diacetate; (E) CONVERTING THE DIACETATE WITH ACETIC ANHYDRIDE IN GLACIAL ACETIC ACID, IN THE PRESENCE OF A STRONG ACID INTO A RIBOSE-1,3,5-TRIACETATE; (F) CONDENSING THE TRIACETATE OBTAINED WITH A PURINE BASE WITH A PURINE BASE IN WHICH ANY FREE PRIMARY AMINO GROUP IS PROTECTED BY ACYLATION IN AN ORGANIC SOLVENT IN THE PRESENCE OF A Lewis acid to form (after splitting the protective acyl group) the desired compound wherein R1 is azide, halogen or alkoxy; (G) OPTIONALLY SEPARATING THE PRODUCT OBTAINED INTO alpha AND beta ANOMERS; AND (H) OPTIONALLY REACTING THE SAID COMPOUND OBTAINED IN STEP (F), IN WHICH R1 is azido, with triphenylphosphine in saturated methanolic ammonia to yield the corresponding compound where R1 is amino.
|