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US 9,676,698 B2Granted
Method of producing ingenol-3-angelate
AssigneeLEO Laboratories Limited
InventorsThomas Hogberg, Gunnar Grue-Sorensen, Xifu Liang, Anne Marie Horneman, Anders Klarskov Petersen
Life of this patent
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Abstract
The present invention relates to methods of producing ingenol-3-angelate (I) from ingenol (II). Furthermore, the invention relates to intermediates useful for the synthesis of ingenol-3-angelate (I) from ingenol (II) and to methods of producing said intermediates.
Claims25
A method of producing a product comprising ingenol-3-angelate (I),
- comprising the steps of:
- esterifying ingenol protected with a dihydroxyl protecting group at the 5 and 20 positions, with angelic acid or a derivative thereof selected from the group consisting of angelic acid, methyl angelate, vinyl angelate, angeloyl chloride, angelic anhydride, angeloyl 2,4,6-trichlorobenzoyl anhydride, [(Z)-2-methylbut-2-enoyl]2,4,6-trichlorobenzoate, and angeloyl 4-nitrobenzoyl anhydride in the presence of a base to produce 5, 20 hydroxyl-protected ingenol-3-angelate (VI), wherein D represents a dihydroxyl protecting group;
- and
- removing the dihydroxyl protecting group at the 5 and 20 positions to produce the product comprising ingenol-3-angelate (I).
1 more element
A method of producing a product comprising ingenol-3-angelate (I),
- comprising the steps of:
- converting angelic acid to angelic anhydride;
- esterifying ingenol protected with a dihydroxyl protecting group at the 5 and 20 positions, with angelic anhydride in the presence of a base to produce 5, 20 hydroxyl-protected ingenol-3-angelate (VI), wherein D represents a dihydroxyl protecting group;
- and
- removing the dihydroxyl protecting group at the 5 and 20 positions to produce the product comprising ingenol-3-angelate (I).
2 more elements
A method of producing a product comprising ingenol-3-angelate (I),
- comprising the steps of:
- esterifying ingenol protected with a dihydroxyl protecting group at the 5 and 20 positions, with angelic anhydride or angelic chloride in the presence of a base to produce 5, 20 hydroxyl-protected ingenol-3-angelate (VI), wherein D represents a dihydroxyl protecting group;
- and
- removing the dihydroxyl protecting group at the 5 and 20 positions to produce the product comprising ingenol-3-angelate (I);
- wherein the product comprises ingenol-3-tiglate and the ingenol-3-angelate (I) at a molar ratio of at most 5:95.
2 more elements
Dependencies are inferred from the claim text.