Studies On Regiospecific Syntheses Of Purine Libraries Via Sulfur Intermediates

Purine derivatives play very important roles in protein regulation and signal transduction. Some of them are regulaters in kinases, G protein and polymerase. Purines have displayed significant anti-tumour, anti-viral and anti-AIDS activities. Amongst the known synthetic purine analogues is 6-mercaptopurine used for treating leukaemia. In addition, the purine core consisting of five possible points of structural diversity is a well-sought scaffold in combinatorial chemistry. A practical synthetic strategy for building purine libraries can aid the study of structure-activity relationship and search of new lead compounds.In this dissertation, libraries of 2,6,8,9- and 6,7,8-tetrasubstituted purines were generated in solution phase via 6-sulfursubstituted pyrimidines as key intermediates. The strategies can be accomplished in solution phase and may be applied to solid phase synthesis through sulfur-linkers. In addition, the reactions of 6-benzylthiopyrimidine-4, 5-diamines and carboxylic acids in presence of polyphosphoric acid were investigated. Both purines and thiazolo[5,4-d] pyrimidines could be obtained selectively when acid-liable groups such as benzyl is used as a sulfur protecting group.The biological activities and syntheses of purine derivatives are reviewed in Chapter One. Purine analogs have been considered a very important class of drug-like molecules. In general, two strategies are applied in preparation of purine libraries. In the first, a preformed purine ring is directly modified. This method has the advantage of allowing straightforward synthesis of highly...