An efficient approach to the synthesis of thymidine derivatives containing phosphate-isosteric methylene acetal linkages

Abstract

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 iodoinium source and protecting groups led to an efficient preparation of thymidine dimers having internucleosidic-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- CH 2 -T dimers. Further, 5′- O-methylthiomethyl-3′- O-methoxyacetyl-N 3-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.