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Copper carbenes alkylate guanine chemoselectively through a substrate directed reaction.

ABSTRACT: Cu(i) carbenes derived from ?-diazocarbonyl compounds lead to selective alkylation of the O6 position in guanine (O6-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 O6-G adducts in biology and biotechnology we expect that Cu(i)-catalyzed O6-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.

SUBMITTER: Geigle SN

PROVIDER: S-EPMC5341205 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Copper carbenes alkylate guanine chemoselectively through a substrate directed reaction.

Geigle Stefanie N SN Wyss Laura A LA Sturla Shana J SJ Gillingham Dennis G DG

Chemical science 20160907 1

Cu(i) carbenes derived from α-diazocarbonyl compounds lead to selective alkylation of the O6 position in guanine (O6-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 O6-G adducts in biology and biotechnology we expect th ...[more]

PMID: 28451197

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