Stereoselective synthesis of nucleoside analogues using bicyclic intermediate
AssigneeBioChem Pharma Inc.
InventorsTarek S. Mansour, Colleen A. Evans, Haolun Jin, M. Arshad Siddiqui, Allan H. L. Tse
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Abstract
The present invention relates to a process for producing predominantly pure cis nucleoside analogues of formula (I), wherein X is S, or O; Y is S, CH.sub.2, O or CH(R); wherein R is azido or halogen; and R.sub.2 is a purine or pyrimidine base; via the coupling of a silylated purine or pyrimidine base in the presence of an appropriate Lewis acid with a bicyclic intermediate of formula (III) wherein Z is S or O; followed by conversion of the resulting intermediate of formula (II) to an alkyl ester and reduction to yield a compound of formula (I). ##STR1##
Claims18
A process for producing predominantly cis-2-carboxylic or thiocarboxylic acid nucleoside intermediates of formula (II) and pharmaceutically acceptable salts or esters thereof:
- ##STR19## wherein;
- X is S, or O;
- Y is S, CH.sub.2, O or CH(R);
- wherein R is azido or halogen;
- Z is S, or O;
- and R.sub.2 is a purine base or a pyrimidine base;
- said process comprising coupling a desired previously silylated or silylated in situ purine base or pyrimidine base with a bicyclic intermediate of formula (III):
- ##STR20## wherein X, Y and Z are as defined above;
- said coupling being achieved using an appropriate Lewis acid in a suitable solvent.
A process for producing a novel intermediate of formula (III):
- ##STR24## wherein;
- X is S, or O;
- Y is S, CH.sub.2, O or CH(R);
- wherein R is azido or halogen;
- and
- Z is S, or O;
- comprising the step of reacting a compound of formula (IV):
- ##STR25## wherein X, Y and Z are as defined above;
- with a mild dehydrating agent.
Dependencies are inferred from the claim text.