Premium
Synthesis of Dihydroxyalkynyl and Dihydroxyalkyl Nucleotides as Building Blocks or Precursors for Introduction of Diol or Aldehyde Groups to DNA for Bioconjugations
Author(s) -
Krömer Matouš,
Bártová Kateřina,
Raindlová Veronika,
Hocek Michal
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201802282
Subject(s) - deoxyribonucleoside , chemistry , aldehyde , dna , uracil , sodium periodate , sonogashira coupling , stereochemistry , combinatorial chemistry , biochemistry , organic chemistry , catalysis , palladium
(3,4‐Dihydroxybut‐1‐ynyl)uracil, ‐cytosine and −7‐deazaadenine 2′‐deoxyribonucleoside triphosphates (dNTPs) were prepared by direct aqueous Sonogashira cross‐coupling of halogenated dNTPs with dihydroxybut‐1‐yne and converted to 3,4‐dihydroxybutyl dNTPs through catalytic hydrogenation. Sodium periodate oxidative cleavage of dihydroxybutyl‐dUTP gave the desired aliphatic aldehyde‐linked dUTP, whereas the oxidative cleavage of the corresponding deazaadenine dNTP gave a cyclic aminal. All dihydroxyalkyl or ‐alkynyl dNTPs and the formylethyl‐dUTP were good substrates for DNA polymerases and were used for synthesis of diol‐ or aldehyde‐linked DNA. The aldehyde linked DNA was used for the labelling or bioconjugations through hydrazone formation or reductive aminations.