Biased photo cleavage of N1-/N6-nitrobenzyl from 2’-hydroxyethyl-adenosine and their DNA/RNA Caged-analogues

Abstract

The protection and deprotection of functional groups are critical steps during the synthesis of complex molecules. The chemo-selective and regio-selective protection-deprotection under mild conditions are always preferred. The photolabile protecting groups have such qualities. For example, o-nitrobenzyl is a versatile photolabile protecting group of amine, alcohol, and carboxylic acid. This report describes the regio-selective N-nitrobenzylation of 2′-tethered-adenosine nucleoside analogue with o-nitrobenzyl bromide, as resultant two new protected nucleosides such as 2′-hydroxylethyl-NBn1A/2′-hydroxylethyl-NBn6A are prepared. Importantly, N-nitrobezylation occurs only at adenine residue, though it is protected. This analogue has a free tethered hydroxyl group at 2′-position and remained unaffected with nitrobenzylation. Furthers, these analogues are incorporated into DNA/RNA oligonucleotides using DNA synthesizer. This report also demonstrates the photocleavage of those nitrobenzyl groups in a regio-specific manner by UV-light (λ365nm). The nitrobenyl of only NBn6A derivatives are cleavable regio-specifically with UV-light. Surprisingly, unusual chemical cleavage of nitrobenzyl of NBn1A-DNA/RNA has found during oligo syntheses. Also, the isomerization of NBn1A-DNA into NBn6A-DNA occurs. Thus only NBn6A derivatives are caged-adenosine analogues. Hence 2′-tethered-NBn6A/-NBn1A derivatives are potential analogues for regulating the biochemical activities with light.