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Stereochemistry of Benzylic Carbon Substitution Coupled with Ring Modification of 2‐Nitrobenzyl Groups as Key Determinants for Fast‐Cleaving Reversible Terminators
Author(s) -
Stupi Brian P.,
Li Hong,
Wang Jinchun,
Wu Weidong,
Morris Sidney E.,
Litosh Vladislav A.,
Muniz Jesse,
Hersh Megan N.,
Metzker Michael L.
Publication year - 2012
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201106516
Subject(s) - chemistry , stereospecificity , hydroxymethyl , ring (chemistry) , stereochemistry , substitution (logic) , medicinal chemistry , organic chemistry , catalysis , computer science , programming language
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.