Journal of Organic Chemistry vol:60 issue:6 pages:1531-1537
1,4-trans-cyclohexanediol has been used as starting material for the synthesis of cyclohexenyl and cyclohexanyl nucleosides functionalized with a OCH2P(O)(OH)(2) moiety in a 1,4-cis relationship with the heterocyclic base. The methodology used is based on the Mitsunobu-type condensation of a conveniently functionalized alcohol with both purines and pyrimidines bases. In all cases (except for cytosine) the natural substituted derivative (N-9 for purines and N-1 for pyrimidines) were obtained as the major isomers. The N-1 cytosine derivative was thus obtained from its uracil analogue. Yields were higher when an allylic alcohol was used in the condensation. Far this reason, cyclohexanyl nucleosides were obtained from their cyclohexenyl analogues by reduction of the 2',3'-double bond. The phosphonomethoxy moiety was introduced prior to the coupling with the heterocyclic base to avoid protection or undesired alkylations of the bases during the derivatization of the 4'-alcohol function.