Synthesis of acyclic nucleoside analogues based on 1,2,4-triazolo [1,5-a]pyrimidin-7-ones by one-step Vorbrüggen glycosylation

摘要

New acyclovir analogues were obtained by reaction of 1,2,4-triazolo[1,5-a]pyrimidin-7-ones 4a-i with (2-acetoxyethoxy)methyl acetate 5 in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as catalyst (Vorbrüggen procedure). Coupling between compounds 4a-f and 5 led to a mixture of N3- and N4-isomers 6 and 7, respectively. On the contrary, the reaction of compounds 4gei with 5 proceeded selectively with formation of N3-isomers only. It was found that the ratio of 6a-f and 7a-f depends on the presence or the absence of N,O-bis(trimethylsilyl)acetamide (BSA). Glycosylated products 6a-f and 7a-f underwent reversible isomerization under TMSOTf treatment. The ratio of glycosylated products of the coupling reaction between 4 and 5 was thermodynamically controlled. A similar reaction occurred if ZnCl_2 was chosen as a catalyst, although lower yields of the acyclic analogues of nucleosides were observed. The glycosylation of other purines (adenine and guanine) can be achieved via the non-BSA modification of the Vorbrüggen procedure.