AN EFFICIENT APPROACH TO THE SYNTHESIS OF THYMIDINE DERIVATIVES CONTAINING PHOSPHATE-ISOSTERIC METHYLENE ACETAL LINKAGES

Iodonium ion promoted condensation of properly protected 3'-O-methylthiomethyl or 3'-O-(4-penten-1-oxymethyl)-thymidine with 3'-O-methoxyacetyl-thymidine, was explored. A judicious choice of the iodonium source and protecting groups led to an efficient preparation of thymidine dimers having intemucleosidic-(3'-5')-methylene bonds. The latter procedure was utilized towards the synthesis, in solution and on a solid support, of DNA-fragments containing one or more T-CH2-T dimers. Further, 5'-O-methylthiomethyl-3'-O-methoxyacetyl-N3-benzoyl-thymidine proved to be a suitable donor for the introduction of 5'-O-methylene acetal-linkages between 2,3,4,6-tetra-O-benzyl-D-glucose, benzyl N-benzyloxycarbonyl-L-serine and dibenzyl phosphate.