cis-Tetrahydrofuran-3,4-diol Structure as a Key Skeleton of New Protecting Groups Removable by Self-Cyclization under Oxidative Conditions

Abstract

A variety of carbonate-type acyl groups having a cis-tetrahydrofuran-3,4-diol (1,4-anhydroerythritol) backbone structure and a TrS or MMTrS group have been examined as new “protected” protecting groups of the 5‘-hydroxyl group of nucleosides. These acyl groups were designed in a manner where they could be deprotected by I₂-promoted removal of the TrS or MMTrS group followed by self-cyclization involving an intramolecular attack of the once-generated neighboring hydroxyl group on the acyl carbon. It turned out that these acyl groups could be introduced into the 5‘-hydroxyl group of a 3‘-O-protected thymidine derivative by use of the corresponding acyl imidazolides or 4-nitrophenyl esters as well as by reaction with carbonyldiimidazole or 4-nitrophenyl chloroformate. Among the acyl groups tested, it was found that the CTFOC group could be easily introduced into the 5‘-hydroxyl group of 3‘-masked deoxyribonucleoside derivatives and rapidly removed under mild conditions using iodine.