SYNTHESIS OF OLIGONUCLEOTIDES Russian patent published in 2012 - IPC C07H21/00 C07D233/58 

FIELD: chemistry.

SUBSTANCE: present invention discloses a method of producing oligonucleotides, involving the following steps: a) providing a hydroxyl-containing compound of formula (A) wherein B is a heterocyclic base and i) R₂ is H, a protected 2-hydroxyl group, F, protected amino group, O-alkyl group, O-substituted alkyl, substituted alkylamino or C4'-O2' methylene bridge; R₃ is OR'₃, NHR"₃, NR"₃R'"_3, wherein R'₃ is a group, protected hydroxyl, protected nucleotide of protected oligonucleotide, R"₃, R'"₃ are independently amine-protecting groups, and R₅ is OH or ii) R₂ is H, protected 2'-hydroxyl group, F, protected amino group, O-alkyl group, O-substituted alkyl, substituted alkylamino, C4'-O2' methylene bridge; R₃ is OH, and R₅ is OR₅ and R'₅ is a hydroxyl-protecting group, protected nucleotide or protected oligonucleotide or iii) R₂ is OH, R₃ is OR'₃, NHR"₃, NR"₃R'"₃, wherein R₃ is a hydroxyl-protecting group, protected nucleotide or protected oligonucleotide, R"₃, R'"₃ are independently amine-protecting groups, and R₅ is OR'₅ and R'₅ is a hydroxyl-protecting group, protected nucleotide or protected oligonucleotide; b) reaction of said compound with a phosphitylation agent in the presence of an activator of formula (I) (activator I), wherein R is alkyl, cycloalkyl, aryl, aralkyl, heteroalkyl, heteroaryl; R₁, R₂ is H or together form a 5-6-member ring; X₁, X₂ are independently N or CH; Y is H or Si(R₄)₃, where R₄ is alkyl, cycloalkyl, aryl, aralkyl, heteroalkyl, heteroaryl; B is a deprotonated acid, to obtain a phosphitylated compound; c) reaction of said phosphitylated compound without separation thereof from a second compound of formula (A), wherein R₅, R₃, R₂, B are independently selected but have the same values as given above, in the presence of an activator II other than I.

EFFECT: improved method.

9 cl, 14 ex, 1 dwg