Synthesis of 2'-O-Methyladenine by A Specific Selective Reaction Strategy
2'-O-Alkylribonucleotides attract significant attention in the antisense drugs due to their piv-otal role in endowing oligonucleotides with high target affinity,enhanced metabolic stability,and supe-rior pharmacokinetic and pharmacodynamic attributes.Especially,the efficient synthesis of 2'-O-meth-yladenosine,a key precursor for the synthesis of second-generation antisense oligonucleotides,is of great importance.The current synthetic approaches have some deficiencies,including high cost and low selectivity.In this paper,a new synthetic route was developed based on exclusively selective reac-tions.Starting with adenosine,this route incorporated acetal protection of the 2'-and 3'-hydroxyl groups,reductive ring-opening of cyclic acetal moiety,the selective methylation of 2'-hydroxyl and hydrogenative debenzylation,and afforded 2'-O-methyladenosine with a one-run overall yield of 36.7％.This strategy exhibits some advantages such as exclusive selectivity,milder reaction condi-tions,cheap and readily available reagents and short synthetic route.It paves the way for new avenues in the regioselective functionalization of hydroxyl groups on the ribose scaffold of nucleoside compounds.
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