Synthesis of 1,2-Disubstituted Carbocyclic Analogs of Pyrimidine and Purine Nucleosides

Abstract

Pyrimidine- and purine-based members of a new class of carbocyclic analogs of 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 prepare other members of the pyrimidine series, namely uracil and thymine derivatives with a methylene between the base and the carbocycle. The uracil derivatives with and without this methylene were halogenated with Cl, Br and I at uracil position 5. The carbocyclic analogs of purine nucleosides with 2-amino-6-chloro purine and 8-azapurine as bases were also efficiently synthesized by construction of the heterocyclic framework on the primary amino group 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 which are present at this position in natural nucleosides.