Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, beta-Fragmentation: Independent Generation and Reactivity of the 2 '-Deoxyadenosin- N6-yl Radical

作者：Zheng Liwei; Griesser Markus; Pratt Derek A^*; Greenberg Marc M^*

来源：Journal of Organic Chemistry, 2017, 82(7): 3571-3580.

DOI：10.1021/acs.joc.7b00093

Formal hydrogen atom abstraction from the nitrogen-hydrogen bonds in purine nucleosides produces reactive intermediates that are important in nucleic acid oxidation. Herein we describe an approach for the independent generation of the purine radical resulting from hydrogen atom abstraction from the N6-amine of 2'-deoxyadenosine (dA.<bold>). </bold>The method involves sequential Norrish Type I photocleavage of a ketone (7b) and beta-fragmentation of the initially formed alkyl radical (8b) to form dA. and acetone. The formation of dA. was followed by laser flash photolysis, which yields a transient with Delta(max) approximate to 340 nm and a broader weaker absorption centered at similar to 560 nm. This transient grows in at =2 x 105 s(-1); however, computations and reactivity data suggest that beta-fragmentation occurs much faster, implying the consumption of dA. as it is formed. Continuous photolysis of 7b in the presence of ferrous ion or thiophenol produces good yields of dA, whereas less reactive thiols afford lower yields presumably due to a polarity mismatch. This tandem photochemical, beta-fragmentation method promises to be useful for site-specific production of dA. in nucleic acid oligomers and/or polymers and also for the production of aminyl radicals, in general<bold>.</bold>

• 出版日期2017-4-7