Asymmetric synthesis of thymine nucleoside analogues based on the isochroman core

Abstract

Diastereoisomeric analogues of d4T having an isochroman core as the glycone moiety have been prepared in seven steps. Starting from phthalaldehyde, two chiral centres analogous to the α/β anomers of D/L sugars were created. The first was obtained enantiomerically pure via asymmetric dihydroxylation and the second via cyclisation of an aldehyde group with a primary hydroxyl group. Retention of chiral integrity at the C 4 site enabled enantiomerically pure nucleoside analogues to be obtained.