2-Methylwyosine, a nucleoside with restricted anti conformation in the east region enforced by nucleobase moiety modification: synthesis and conformational analysis by NMR and molecular dynamics.
We synthesized a new 2-methyl derivative of wyosine using a multistep procedure starting from guanosine. We examined different synthetic paths and optimized the conditions for each step. Based on MD calculations and analysis of the (3) J (HH) and J (C1'H1') of the ribose moiety, we discovered that the sugar part adopted conformation specific for the East region rarely occurring in solution. This unusual conformational preference is probably due to steric repulsions between the methyl group at position 2 and the 5'-CH(2)OH group. We observed that N-glycosidic bond stability weakened 14-fold upon the introduction of the methyl group in position 2 compared with wyosine.
Laboratory of Nucleoside Chemistry, Institute of Bioorganic Chemistry PAS, Poznan, Poland. danibari@ibch.poznan.pl
Daniel
D
Baranowski
Bozenna
B
Golankiewicz
Wojciech
W
Folkman
Mariusz
M
Popenda
D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation
D006151:Guanosine; D006851:Hydrochloric Acid