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US 7,071,328 B2Granted
Method for the preparation of 21-hydroxy-6,19-oxidoprogesterone (21 oh-6op)
AssigneeApplied Research System ARS Holding N.V.
InventorsGerardo Burton, Carlos P. Lantos, Adriana Silvia Veleiro
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Abstract
The present invention relates to a novel method for preparing 21-hydroxy-6,19-oxidopro-gesterone (21OH-6OP) and/or its 21-acetate, 21-propionate, 21-hemisuccinate, 21-phosphate, 21-oleate derivatives. 21OH-6OP and its ester derivatives are antiglucocorticoids for the treatment or prophyl axis of diseases associated to an excess of glucocorticoids, in particular for treating Cushing's syndrome, iatrogenic hypercortisolism or depression.
Claims12
A method of preparing 21-hydroxy-6,19-oxidoprogesterone (1) or an acyl or phosphate derivative thereof.
- the method comprising
- a) protecting the C-3 hydroxy group of 21-acetoxypregnenolone through formation of a labile ester;
- b) obtaining the bromohydrin product thereof, by addition of a bromine and a hydroxy group onto the double bond of position of C5-C6 of the ester protected 21-acetoxy-pregnenolone;
- c) performing an intramolecular cyclization with the C19 atom with the “Suarez-reagent” (diacetoxyiodobenzene) and iodine under irradiation, thus obtaining the 6,19 oxido-bridge within the scaffold;
- d) performing a selective hydrolysis, followed by an oxidation, to obtain a bromo-ketone;
- e) performing a hydrolysis of the bromoketone resulting from step d) to obtain 21-hydroxy-6,19-oxidoprogesterone (1);
- and optionally
- f) reacting compound (1) with an acylating agent or phosphorylating agent.
5 more elements
A method for preparing (6)
- comprising the step of performing an intramolecular cyclisation between the 6-OH and the C19 of the molecule (5)
- comprising the step of performing an intramolecular cyclisation between the 6-OH and the C19 of the molecule (5) by photoreaction with diacetoxyiodobenzene and I2.
Dependencies are inferred from the claim text.