| 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 {dollar}gamma{dollar}-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. |
