Diastereoselective synthesis of phosphite triesters and phosphorothioates

The diastereoselective synthesis of phosphite triesters and related phosphorothioate triesters and diesters has been investigated, with the goal of synthesizing diastereomerically pure DNA phosphorothioates.Towards this end, the elaboration of a new heterobicyclic structure, imidazo-oxazaphosphorine such as 56, is reported. This unstable intermediate led to the highly diastereoselective synthesis of simple phosphite triesters upon reaction with various alcohols.Two new types of sterically hindered chiral oxazaphosphorinanes 135 and 146 were then synthesized from cholesterol and camphor respectively. These structures, derived from $ gamma$-aminoalcohols possessing a tertiary alcohol function, could be isolated and characterized. They revealed very reactive in acidic conditions and led to rearrangements.Finally, oxazaphosphorinane 188 derived from 1,2-O-isopropylidene-D-xylofuranose, was synthesized and characterized. The introduction of a participating group adjacent to the leaving phosphorothioate group led to the fast release of the phosphorothioate moiety. This new chiral auxiliary was successfully used as a precursor in the diastereoselective synthesis of a T-T phosphorothioate dimer, in a diastereomeric ratio of 28.5:1.* ftn*Please refer to dissertation for diagrams