METHOD FOR PREPARING NEW FLAVIN DERIVATIVES - SYNTHESIS OF FLAVIN THYMINE NUCLEOTIDES AND FLAVIN-OLIGONUCLEOTIDE ADDUCTS

In 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 w ere 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 12 a,b, flavin-thymine nucleotides and flavin-oligonucleotide adducts wer e synthesized for the first time. The versatility of the method was de monstrated in the oxidation step with the synthesis of the flavin-thym ine nucleotides 15-17 possessing a phosphodiester, a phosphorothioate, and a methyl phosphate linkage, respectively. This method is of gener al interest with regard to the extensive research developed for prepar ing flavin analogs and modified oligonucleotides possessing interestin g biological or/and catalytic properties.