Nucleotides - Part LV - Synthesis and application of a novel linker for solid-phase synthesis of modified oligonucleotides

摘要

Various bifunctional amino-protecting groups such as the phthaloyl, succinyl, and glutaryl group were investigated as potential linker molecules for attachment to solid-support materials. Pentane-1.3,5-tricarboxylic acid 1,3-anhydride (16) offered the best properties and reacted with the amino groups of differently sugar-protected adenosine (see 20 and 22), cytidine (see 29), and guanosine derivatives (see 32) to the corresponding 2-(2-carboxyethyl)glutaryl derivatives 23, 24. 30, and 33. The usefulness of the new linker-type molecules was demonstrated by the solid-support synthesis of the potentially antivirally active 3'-deoxyadenylyl-(2'-5')-2'-adenylic acid 2'-{2-[andenin-9-yl)methoxy]ethyl} ester (38) starting from the 2'-end with N-6,N-6-[2-(2-carboxyethyl)glutaryl]-9- {{2-[(4,4'-dimethoxytrityl)oxy]ethoxy}methyl}adenine (12). [References: 28]