Copper carbenes alkylate guanine chemoselectively through a substrate directed reaction

Cu(i) carbenes derived from α-diazocarbonyl compounds lead to selective alkylation of the O position in guanine (O -G) in mono- and oligonucleotides. Only purine-type lactam oxygens are targeted - other types of amides or lactams are poorly reactive under conditions that give smooth alkylation of gu...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2017-01, Vol.8 (1), p.499-506
Main Authors: Geigle, Stefanie N, Wyss, Laura A, Sturla, Shana J, Gillingham, Dennis G
Format: Article
Language:English
Subjects:
Alkylation
Amides
Biology
Biotechnology
Carbenes
Damage
Guanines
Transition metals
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Summary:Cu(i) carbenes derived from α-diazocarbonyl compounds lead to selective alkylation of the O position in guanine (O -G) in mono- and oligonucleotides. Only purine-type lactam oxygens are targeted - other types of amides or lactams are poorly reactive under conditions that give smooth alkylation of guanine. Mechanistic studies point to N7G as a directing group that controls selectivity. Given the importance of O -G adducts in biology and biotechnology we expect that Cu(i)-catalyzed O -G alkylation will be a broadly used synthetic tool. While the propensity for transition metals to increase redox damage is well-appreciated, our results suggest that transition metals might also increase the vulnerability of nucleic acids to alkylation damage.
ISSN:2041-6520
2041-6539
DOI:10.1039/c6sc03502g