METHOD OF PRODUCING INGENOL-3-ANGELATE Russian patent published in 2016 - IPC C07C67/08 C07C67/297 C07C69/533 C07D319/08 

FIELD: chemistry.

SUBSTANCE: present invention relates to method of producing ingenol-3-angelate (I) from ingenol (II). Invention also relates to intermediate products used for synthesis of ingenol-3-angelate (I) from ingenol (II), and methods of producing said intermediate products. Method of producing ingenol-3-angelate (1aR,2S,5R,5aS,6S,8aS,9R,10aR)-5,5a-dihydroxy-4-(hydroxymethyl)-1,1,7,9-tetramethyl-11-oxo-1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8A-methanocyclopente[a]cycloprope[e]cyclodecen-6-yl ester 2-methyl-2(Z)-butenoic acid) of formula (I) from ingenol of formula (II) includes following steps: (a) reaction of one or both of hydroxyl groups in positions 5 and 20 ingenol with suitable hydroxyl protecting agents, which can be identical or different, to obtain compound of general formula (III) or (IV) in which R₁ represents hydrogen or hydroxyl protecting group and R₂ represents hydrogen or hydroxyl protecting group, provided that R₁ and R₂ simultaneously represent hydrogen, or in which D is hydroxyl protecting group, (b) esterification hydroxyl group in position 3 compounds (III) or (IV) to obtain compounds of general formula (V) or (VI), in which R₁, R₂ and D have values given above, and (c) removing hydroxyl protecting groups R₁ or R₂, or R₁ or R₂, or the compounds (V) or (VI) to obtain ingenol-3-angelate of formula (I).

EFFECT: method allows to produce end product with good output.

25 cl, 11 tbl, 29 ex