CHIRAL r, 2'-5£CO-NUCLE OSIDES: SYNTHESIS OF D AND L- THkËITOL-2 '-O-METHYLENYL NUCLEOSIDES

Seo>-nucleoside derivatives of adenine, cytosine, guanine and thymine with a D or L-threitol side-chain configuration have been synthesized from D or L dimethyl tartarate respectively. Biological evaluation of the four enantiomeric pairs of nucleosides revealed they were inactive against various viruses in cell cultures. The lack of rational structure-activity relationships in antiviral chemotherapy is at the origin of an intensive synthetic work especially in the field of nucleosides 1. In this respect the synthesis of new acyclic nucleosides is of uppermost interest owing to the well established activity of some members of this important class of compounds as antiviral agents^. Recent studies with both racemic and chiral nucleoside analogues3 (i.e. carba-2'-deoxyguanosine4, DHBG5 and DHPG6) have shown that the antiviral activity usually resides in only one of the two enantiomers. Although the syntheses of a few chiral 1', 2'-seco-nucIeosides have been reported7'10, erythritol nucleoside derivatives i.e. 9-((l\ 3'(S)- dihydroxy-2'(R)-butoxy)methyl)guanine and the N-l derivative of uracil are only fully described11 in these series. This paper is devoted to a straightforward synthesis of homochiral 1', 2'-sec0-nucleosides 13 and 14 having a L or D threitol side-chain with four nucleobases i.e. adenine, cytosine, guanine and thymine (Figure 1).