A simple method for C-6 modification of guanine nucleosides

Area of Science:

• Organic Chemistry
• Nucleoside Chemistry

Background:

• Guanosine and 2'-deoxyguanosine are fundamental components of nucleic acids.
• Modification of nucleosides is crucial for developing novel therapeutic agents and biochemical tools.
• Introducing substituents at the C-6 position of guanosine presents synthetic challenges.

Purpose of the Study:

• To report a facile and efficient method for C-6 functionalization of guanosine and 2'-deoxyguanosine.
• To synthesize stable O(6)-(benzotriazol-1-yl) guanosine derivatives as versatile intermediates.
• To demonstrate the utility of these intermediates in generating diverse C-6 modified 2-amino purine nucleoside analogues.

Main Methods:

• Protection of guanosine and 2'-deoxyguanosine using tert-butyldimethylsilyl groups.
• Conversion of protected nucleosides to O(6)-(benzotriazol-1-yl) derivatives using BOP and DBU.
• Reaction of the O(6)-(benzotriazol-1-yl) intermediates with various nucleophiles.

Main Results:

• A simple, one-step transformation was achieved for C-6 modification.
• Stable and easily isolable O(6)-(benzotriazol-1-yl) guanosine derivatives were obtained.
• Good yields of C-6 modified 2-amino purine nucleoside analogues were achieved through nucleophilic substitution.

Conclusions:

• The reported method offers a convenient route for synthesizing C-6 substituted guanosine analogues.
• The O(6)-(benzotriazol-1-yl) intermediates are valuable synthons for medicinal chemistry and chemical biology.
• This approach facilitates the generation of diverse libraries of modified nucleosides.