jo962361w_si_001.pdf (336.52 kB)
Method for Preparing New Flavin Derivatives: Synthesis of Flavin−Thymine Nucleotides and Flavin−Oligonucleotide Adducts
journal contribution
posted on 1997-05-30, 00:00 authored by Christelle Frier, Jean-Luc Décout, Marc FontecaveIn order to link to the 5‘-end of oligonucleotides the
flavin analogs 9a,b possessing only one
terminal
hydroxy group on the side chain, the phosphoramidite and the
H-phosphonate coupling methods
were developed. Surprisingly, after reaction of compounds
9a,b with 2-cyanoethyl
N,N-diisopropylchlorophosphoramidite, the flavin phosphoramidates 11a,b
were isolated instead of the expected
phosphoramidite derivatives 10a,b. A very efficient
photooxidation process occurred probably during
the isolation of the products. From the prepared flavin
H-phosphonates 12a,b, flavin−thymine
nucleotides and flavin−oligonucleotide adducts were synthesized for
the first time. The versatility
of the method was demonstrated in the oxidation step with the synthesis
of the flavin−thymine
nucleotides 15−17 possessing a phosphodiester,
a phosphorothioate, and a methyl phosphate
linkage, respectively. This method is of general interest with
regard to the extensive research
developed for preparing flavin analogs and modified oligonucleotides
possessing interesting biological
or/and catalytic properties.