• Open Access

Stereochemistry of Benzylic Carbon Substitution Coupled with Ring Modification of 2-Nitrobenzyl Groups as Key Determinants for Fast-Cleaving Reversible Terminators


  • This work was supported in part by the National Institutes of Health (R01 HG003573). We thank Sherry Metzker from LaserGen for critical reading of the manuscript.


original image

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.