Photochemistry of 4'-benzophenone-substituted nucleoside derivatives as models for ribonucleotide reductases: Competing generation of 3'-radicals and photoenols

Thomas E. Lehmann, Gerhard Müller, Albrecht Berkessel

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Ribonucleotide reductases (RNRs) catalyze the 2'-reduction of ribonucleotides, thus providing 2'-deoxyribonucleotides, the monomers for DNA-biosynthesis. The current mechanistic hypothesis for the catalysis effected by this class of enzymes involves a sequence of radical reactions. A 3'-hydrogen abstraction, effected by a radical at the enzyme's active site, is believed to initiate the catalytic cycle. As models for this substrate- enzyme interaction, the photochemically induced intramolecular hydrogen abstraction in a series of 4'-benzophenone-substituted nucleoside analogues was studied. Model compounds with hydroxy-, methoxy-, mesyloxy-groups or a cyclic carbonate in 2'- and 3'-positions were investigated. Depending on the substitution pattern, two different types of photoproducts were observed: Those which result from photoenol formation (γ-H-abstraction) and those which result from abstraction of the 3'-H-atom (δ-H-abstraction). Photoenol formation was further supported by H/D-exchange experiments. Thus, the 3'-H- abstraction postulated as the initial step in RNR action was successfully modeled by photolysis of 4'-benzophenone-substituted nucleoside analogues. The regioselectivity of the photochemical H-abstraction and thus of the product distribution as a function of the 2'- and 3'-substituents was rationalized on the basis of a conformational analysis of the four model systems, utilizing molecular mechanics simulations.

Original languageEnglish
Pages (from-to)2508-2516
Number of pages9
JournalJournal of Organic Chemistry
Volume65
Issue number8
DOIs
StatePublished - 21 Apr 2000
Externally publishedYes

Fingerprint

Dive into the research topics of 'Photochemistry of 4'-benzophenone-substituted nucleoside derivatives as models for ribonucleotide reductases: Competing generation of 3'-radicals and photoenols'. Together they form a unique fingerprint.

Cite this