NEW METHOD FOR SYNTHESIS OF AMANITINES Russian patent published in 2023 - IPC C07D487/04 A61K47/68 A61P35/00 C07K7/64 A61K38/12 

FIELD: chemistry.

SUBSTANCE: invention describes the new methods for the synthesis of amanitin derivatives having a hydroxy group attached to the central tryptophan fragment, as well as to a hydroxy-substituted derivative of 2-carboxy-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole according to formula I

in which R1 is chosen from C_1-2-alkyl; P₁ represents hydrogen or a protective group; P₂ is hydrogen or a protecting group and R 2 is chosen from OH, OR 1 and a polypeptide chain of 1-7 amino acid residues, where the protecting group, if present, is independently chosen from Boc, PhCH₂ OCO-, CH₂ =CHCH₂ O-CO- and trityl.

EFFECT: new derivatives of amanitin are obtained, having a hydroxy group attached at position 4', 5'', 6' or 7' a central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates for the treatment of cancer.

19 cl, 1 ex, 15 dwg