CHIRAL DIACYLHYDRAZINE LIGANDS FOR MODULATION OF EXOGENOUS GENES EXPRESSION BY ECDYSONE-RECEPTOR COMPLEX Russian patent published in 2018 - IPC C07C241/04 C07C243/38 C07C281/02 C07C271/08 C07D213/82 C07D307/68 C07D317/68 C07D319/18 C07D333/38 C12N15/82 A61K31/166 A61K31/27 A61K31/341 A61K31/357 A61K31/36 A61K31/381 A61K31/44 

FIELD: biotechnology.

SUBSTANCE: invention relates to a method for preparation of an enantiomerically enriched compound with Formula III , wherein A is (C₁-C₆)alkyl-O-, phenyl- C₁-C₆)alkyl-O-; aryl selected from phenyl, naphthyl, benzo 1,3]dioxole, 2,3-benzo[1,4]dioxin which is optionally substituted by 1 to 3 substituents, where the substituents are selected from (C₁-C₆) alkyl, (C₃-C₇) cycloalkyl, (C₁-C₆)alkyl-O-, hydroxy, amino and halo; or heteroaryl having four or five carbon atoms and one heteroatom selected from oxygen, nitrogen and sulfur, which is optionally substituted by 1 to 3 substituents, where the substituents are selected from (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, (C₁-C₆)alkyl-O-, hydroxy, amino and halo; B is phenyl optionally substituted by 1 to 3 substituents, where the substituents are selected from (C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, (C₁-C₆)alkyl-O-, hydroxy, amino and halo; and R¹ and R² independently represent (C₁-C₆)alkyl, phenyl-(C₁-C₆)alkyl-, hydroxy-(C₁-C₆)alkyl, (C₃-C₇)cycloalkyl, (C₂-C₆)alkenyl or (C₂-C₆)alkynyl; provided that R¹ differs from R²; where the absolute configuration of the asymmetric carbon atom carrying R¹ and R², is an R-configuration; including (a) reaction of Formula XI acylhydrazine with Formula XII ketone to form a compound of Formula XIII , where R¹ differs from R², (b) reduction of the Formula XIII compound in the presence of a chiral catalyst to form a Formula R-XIV compound and (c) reaction of the Formula R-XIV compound with the Formula B-CO-LG compound, wherein LG is a leaving group, forming a compound with Formula III.

EFFECT: chiral diacylhydrazine ligands for genome modulation.

6 cl, 25 dwg, 11 tbl