Synthesis of 1,2-disubstituted carbocyclic analogs of pyrimidine and purine nucleosides

Pydmidine- and purine-based members of a new class of carbocyclic analogs o f nucleosides with 1,2-disubstituted carbocycles were synthesized. For the synthesis of the thymidine analog 3, construction of the base on the amino group of (2-aminocyclopentyl)methanol was more efficient than condensation of the base with a diol. The former strategy was accordingly used to prepar e other members of the pyrimidine series, namely uracil and thymine derivat ives with a methylene between the base and the carbocycle. The Uracil deriv atives with and without this methylene were halogenated with Cl, Br and I a t uracil position 5. The carbocyclic analogs of purine nucleosides with 2-a mino-6-chloro purine and 8-azapurine as bases were also efficiently synthes ized by construction of the heterocyclic framework on the primary amino gro up of the appropriate amino alcohol. The chlorine in position 6 of the base was then replaced in good yields by an amino or hydroxyl group, both of wh ich are present at this position in natural nucleosides.