| 摘要 |
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 |
