Protection of the guanine residue during synthesis of 2′-O-alkylguanosine derivatives

Abstract

Highly selective 2′-O-alkylation of 3′,5′-O-(tetraisopropyldisiloxane-1,3-diyl) guanosine has been achieved by using an alkyl halide and a sterically hindered strong organic base, when the 6-O atom is protected with either a 2-nitrophenyl or a tert-butyldiphenylsilyl group prior to the alkylation. A minimum of chromatography is required, the yields are high and none of the unwanted isomer is produced. Moreover, the highly versatile intermediates enable the synthesis of several new 2′-O-alkylguanosine derivatives as well as base-modified analogues.

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