Solid-phase synthesis of purine derivatives

Abstract

This thesis reports the development of novel methodologies for the solid phase synthesis (SPS) of purine derivatives. The first project involves the SPS of 2,9-disubstituted-6-oxopurines using Wang resin. The synthetic strategy was designed to load the 6-chloropurine scaffold directly onto the solid support via an ether linker. After combinatorial modifications at N9 and C2, the resin was cleaved and 2,9-disubstituted-6-oxopurines were released. The second project focuses on the investigation of the regioselective SPS of N7-substituted purine using REM resin. The synthetic strategy was devised to anchor the REM resin at N9 of 6-chloropurine, leaving N7 as the steric priority for alkylation. Further modification at N1 followed by cleavage resulted in 1,7-disubstituted-6-oxopurines being obtained.The third project centers on widening the SPS of purines based on the purine ring formation strategy. The synthetic strategy was designed to load the 5-amino-4,6-dichloropyrimidine onto BOBA resin to construct the diamine key intermediate. Using this intermediate, various substituted purines including 1,7,8-trisubstituted purines, 8-unsubstituted purines, 8-azapurines and [i]-condensed purines could be prepared.