posted on 2024-01-16, 16:15authored byZhenqiang Xia, Dasharath Kondhare, Somnath Shivaji Chandankar, Sachin A. Ingale, Peter Leonard, Frank Seela
The
functionalization in position-7 of 7-deazaisoguanine and 7-deazapurin-2,6-diamine
ribo- and 2′-deoxyribonucleosides by halogen atoms (chloro,
bromo, iodo), and clickable alkynyl and vinyl side chains for copper-catalyzed
and copper-free cycloadditions is described. Problems arising during
the synthesis of the 7-iodinated isoguanine ribo- and 2′-deoxyribonucleosides
were solved by the action of acetone. The impact of side chains and
halogen atoms on the pKa values and hydrophobicity
of nucleosides was investigated. Halogenated substituents increase
the lipophilic character of nucleosides in the order Cl < Br <
I and decrease the pK values of protonation. Photophysical
properties (fluorescence, solvatochromism, and quantum yields) of
azide–alkyne click adducts bearing pyrene as sensor groups
were determined. Pyrene fluorescence was solvent-dependent and changed
according to the linker lengths. Excimer emission was observed in
dioxane for the long linker adduct. Bioorthogonal inverse-electron-demanding
Diels–Alder cycloadditions (iEDDA) were conducted on the electron-rich
vinyl groups of 7-deazaisoguanine and 7-deazapurin-2,6-diamine nucleosides
as dienophiles and 3,6-dipyridyl-1,2,4,5-tetrazine as diene. The initially
formed complex reaction mixture of isomers could be easily oxidized
with iodine in tetrahydrofuran (THF)/pyridine leading to single aromatic
tetrazine adducts within a short time and in excellent yields.