STEREOSELECTIVE SYNTHESIS OF 2'-DEOXY-BETA-D-THREO-PENTOFURANOSYL NUCLEOSIDES BY THE NBS-PROMOTED COUPLING REACTION OF THIOGLYCOSIDES WITH SILYLATED HETEROCYCLIC BASES

The NBS-promoted coupling reaction of phenyl idene-2-deoxy-1-thio-alph a-D-threo-pentofuranoside (5e) with silylated pyrimidine bases was fou nd to proceed in a highly stereoselective manner (alpha:beta = 1:24-0: 1) to afford 2'-deoxy-beta-D-threo-pentofuranosyl pyrimidine nucleosid es in satisfactory yields. The highly stereoselective outcome is thoug ht to result from an in situ anomerization-type mechanism, in which in timate ionic intermediates would be in equilibrium and anomerize to th e sterically preferable a form. A subsequent S(N)2 type attack to the intermediate will lead to the beta-nucleosides. By using this method, the synthesis of L-nucleosides, 1-(2-deoxy-beta-L-threo-pentofuranosyl )thymine and cytosine derivatives, was also demonstrated by starting f rom the L-enantiomer of the thioglycoside. On the other hand, the reac tion with purine bases was accompanied by the production of undesirabl e N-7 regioisomers besides the desired N-9 products. The product distr ibution of the regioisomers was, however, proved to change with reacti on time. For instance, a long reaction period allowed the thermodynami cally stable N-9 isomers to be exclusively produced with moderate sele ctivity (alpha:beta = 1:2-1:4.8). The isolated yields of the 9-beta is omers after purification were acceptable for practical use.