METHOD FOR PREPARING PHOSPHOTHIOATE ANALOGS OF OLIGODEOXYRIBONUCLEOTIDES

摘要

FIELD: organic chemistry, biochemistry, chemical technology.;SUBSTANCE: invention relates to a method for synthesis of phosphothioate analogs of oligodeoxyribonucleotides of the general formula (I); wherein B means residue of thymine, cytosine, adenine or guanine; n = 1-20 on a solid-phase carrier. Method involves washing out a carrier with nucleoside fixed on it with a solvent wherein nucleoside comprises 5'-O-protective group, removal of 5'-O-protective group of nucleoside bound with a carrier, repeated washing out a solid-phase carrier with solvent wherein carrier comprises a nucleoside fixed on it and comprising 5'-hydroxyl group, mixing N,5'-protected deoxyribonucleoside-3'-H-phosphonates with activating reagent, feeding this mixture into reactor, condensation with 5'-hydroxyl group of terminal nucleoside bound with a carrier, repeating these procedures up to preparing protected oligodeoxyribonucleoside H-phosphonate with the required number of monomeric links, treatment of synthesized compound with sulfur solution followed by treatment with aqueous ammonia for detachment of a carrier and removal of N-protecting group. Mixing N,5'-protected deoxyribonucleoside-3'-H-phosphonates with activating agent and feeding the mixture into reactor is carried out for 0.4-0.5 s, and condensation with 5'- hydroxyl group of terminal nucleoside is carried out for 2-3 s and these procedures are repeated 14-20 times at temperature 30-35°C of reagents at all steps of synthesis. Invention provides enhancing output of the method based on reducing time in synthesis of an intermediate substance and economy of used reagents. Synthesized analogs can be used in molecular biology and medicine as the parent compounds for synthesis of phosphothioate analogs of oligodeoxyribonucleotide reagents.;EFFECT: improved method of synthesis.;2 ex