Nucleobase-Functionalized 7-Deazaisoguanine and 7-Deazapurin-2,6-diamine Nucleosides: Halogenation, Cross-Coupling, and Cycloaddition

被引:3
作者
Xia, Zhenqiang [1 ]
Kondhare, Dasharath [1 ]
Chandankar, Somnath Shivaji [1 ]
Ingale, Sachin A. [1 ]
Leonard, Peter [1 ]
Seela, Frank [1 ,2 ]
机构
[1] Ctr Nanotechnol, Lab Bioorgan Chem & Chem Biol, D-48149 Munster, Germany
[2] Univ Osnabruck, Inst Chem neuer Mat, Lab Organ & Bioorgan Chem, D-49069 Osnabruck, Germany
关键词
BASE-PAIRING PROPERTIES; OLIGONUCLEOTIDE DUPLEXES; 7-DEAZAPURINE RIBONUCLEOSIDES; BUILDING-BLOCKS; DNA; ISOGUANOSINE; ISOGUANINE; PARALLEL; 2'-DEOXYISOGUANOSINE; TETRAZINES;
D O I
10.1021/acs.joc.3c02514
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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 pK(a) 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.
引用
收藏
页码:1807 / 1822
页数:16
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