Synthesis of 2-substituted 2'-deoxyguanosines and 6-O-allylguanines via the activation of C-2 by a trifluoromethanesulfonate group

A new general synthesis of 2-substituted 2'-deoxyguanosine and 6-O-allylguanine analogues is reported. 2-O-Trifluoromethylsulfonyl-6-O-allyl-3',5'-bis-O- (tert-butyldimethylsilyl)-2'-deoxyxanthosine 8 can be converted into a 2-substituted 2'-deoxyguanosine analogue by substitution of the triflate (trifluoromethanesulfonate) moiety using a selected nucleophile, followed by deprotection. Therefore, a 2'-deoxyguanosine may overall be converted into a 2-substituted 2'-hypoxanthosine analogue in seven steps. Similar methodology has been used to synthesize 2-substituted 6-O-allylguanines which are of particular interest as potential resistance-modifying agents in cancer chemotherapy.