Chemical synthesis of hydroxymethylphosphonate alpha-DNA.

In this paper, we report the synthesis of hydroxymethylphosphonate alpha-DNAs and related compounds by use of the H-phosphonate method. These modified alpha-DNAs were designed to improve the inherent poor solubility of well-known methylphosphonate alpha-DNAs by introduction of a more hydrophilic hydroxymethylphosphonate function. The hybridization ability of hydroxymethylphosphonate alpha-DNAs was studied. We also report a novel strategy for the synthesis of alpha-thymidine by use of C1'-epimerization. The details of the neighboring effect of various 5'- and 3'-hydroxyl protective groups such as carbamoyl groups on the beta-->alpha conversion will be described.