64643-76-1Relevant articles and documents
PROCESS FOR OBTAINING 3,14-DIACETYLOXYMORPHONE FROM ORIPAVINE
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Page/Page column 22, (2018/01/17)
The present invention relates to a new process for obtaining 3,14-diacetyloxymorphone from oripavine, a process to transform the obtained 3,14-diacetyloxymorphone into a noroxymorphone and a process to transform said noroxymorphone into naloxone, naltrexone, nalbuphine, nalfurafine or nalmefene.
METHOD FOR PURIFYING NOROXYMORPHONE COMPOUNDS
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Page/Page column 16-17, (2008/06/13)
The invention relates to a method for purifying plant extracts that are substantially composed of noroxymorphone compounds and that contain in the a,? position unsaturated noroxymorphones as contaminants. The method comprises the following steps: (a) reacting the plant extract or the product of a subsequent step in synthesis of a selected noroxymorphone compound in a reaction by which the hydroxyl groups present in the mixture are converted to leaving groups of the formula -OR2, wherein R2 represents the inserted group of the leaving group; (b) optionally removing the leaving groups; (c) subjecting the mixture thereby obtained to a selective hydration so that a saturated bond is formed in the α,? position of the unsaturated noroxymorphone compound and the remaining present leaving groups are each converted to a hydroxyl group; and then optionally (d) isolating the pure noroxymorphone compound. The invention also relates to the manufacture of the noroxymorphone so purified to naltrexone or naloxone or to a salt of these compounds or to a quaternary derivative of these compounds. The invention finally relates to the pharmaceutical compositions comprising the inventive compound.
Diastereomeric 6-desoxy-6-spiro-α-methylene-γ-butyrolactone derivatives of naltrexone and oxymorphone. Selective irreversible inhibition of naltrexone binding in an opioid receptor preparation by a conformationally restricted Michael acceptor ligand
Koolpe,Nelson,Gioannini l.,Angel,Simon
, p. 1718 - 1723 (2007/10/02)
The diastereomeric 6-desoxy-6-spiro-α-methylene-γ-butyrolactone derivatives of naltrexone (4a and 5a) and of oxymorphone (4b and 5b) were prepared from their parent ketones. Diastereomers 4a and 4b were obtained from the 3,14-diacetate derivatives of naltrexone and oxymorphone by reaction with the Reformatsky reagent prepared from methyl α-(bromomethyl)acrylate. Deacetylation with methanol completed the synthesis. Diastereomers 5a and 5b were obtained from two oxiranes, respectively. The oxiranes were allowed to react with the sodium salt of ethyl acetoacetate, followed by methenation of and deprotection to complete the synthesis of 5a and 5b, respectively. Compound 5a was the most potent agent tested in competition against [3H]naltrexone in the opioid radioreceptor assay. At a concentration of 5 nM this compound produced a 50% inhibition of binding. The majority of this inhibition (30%) was irreversible, i.e., it remained even after extensive washing of the membrane preparation in the presence and absence of Na+. Naloxone protected against this irreversible effect. The data suggest a receptor nucleophile, perhaps a sulfhydryl group, is located where it can add to the α,β-unsaturated carbonyl system of 5a.
