Stereochemistry of benzylic carbon substitution coupled with ring modification of 2-nitrobenzyl groups as key determinants for fast-cleaving reversible terminators

Abstract

A complete set of 2-nitrobenzyl-modified reversible terminators have been developed, which upon exposure to UV light generate natural hydroxymethyl nucleotides (see scheme). The combination of a stereospecific (S)-tert-butyl group (R) at the benzylic carbon and a 5-OMe group (R′) on the 2-nitrobenzyl ring substantially increase the rate of photochemical cleavage. For 7-deaza-7-hydroxymethyl-2′-deoxyguanosine, these modifications led to a rate increase of more than one order of magnitude. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.