SYNTHESIS OF 3'-DIALKYLAMINO-2',3'-DIDEOXYNUCLEOSIDES FROM A 2,3'-ANHYDROTHYMIDINE OR AN ALPHA,BETA-UNSATURATED ALDEHYDE

Reaction of 2,3'-anhydro-5'-O-(4-methoxybenzoyl)thymidine (2) with mor pholine, piperidine and piperazine gives the corresponding deprotected 3'-dialkylaminonucleosides 3a-c in 7-47% yield and with 1,2,4-triazol e the protected analog 4 in 8% yield. The reaction of 2 with triazole, in the presence of phosphoryl trichloride cleaved the glycosidic bond and triazole replaced the nucleobase to give the glycosylated alpha a nd beta nucleosides 5 and 6 with the 2,3'-ether bond intact to the pyr imidine ring, but also with a triazole ring substituted into the 4-pos ition of the pyrimidine ring. (2E,4S)-5-Acetoxy-4-hydroxy-2-pentenal ( 10), readily accessible from tri-O-acetyl-D-glucal (9), reacted with p iperidine and morpholine to give anomeric mixtures of 2,3-dideoxy-3-pi peridino and y-3-morpholino-alpha,beta-D-erythro-pentofuranoses which were acetylated to give 11. Trimethylsilyl trifluoromethanesulfonate c atalyzed reactions of 11 with silylated forms of thymine and N-4-isobu tyrylcytosine gave, after chromatographic separation, the acetylated D -erythro nucleosides, which by treatment with methanolic ammonia were deprotected to the free nucleosides 3, 12-14.