64643-76-1Relevant academic research and scientific papers
PROCESS FOR OBTAINING 3,14-DIACETYLOXYMORPHONE FROM ORIPAVINE
-
Page/Page column 29, (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.
PROCESS FOR THE PREPARATION OF MORPHINE ANALOGS VIA METAL CATALYZED N-DEMETHYLATION/FUNCTIONALIZATION AND INTRAMOLECULAR GROUP TRANSFER
-
Page/Page column 11, (2012/11/13)
The present application is directed to an efficient conversion of C-14 hydroxylated morphine alkaloids to various morphine analogs, such as naltrexone, naloxone and nalbuphone. One feature of this process is an intramolecular functional group transfer from the C-14 hydroxyl to the N-17 nitrogen atom following a palladium-catalyzed N-demethylation.
METHOD FOR PURIFYING NOROXYMORPHONE COMPOUNDS
-
Page/Page column 15-16, (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.
METHOD FOR PURIFYING NOROXYMORPHONE COMPOUNDS
-
Page/Page column 12, (2008/06/13)
The invention relates to a method for purifying oxymorphone compounds of formula (II) or a mixture of compounds of formula (II), and said compounds of formula (II) or the mixture of compounds of formula (II) which contain at least one corresponding a,?-unsaturated compound as an impurity, wherein R1, R2 and R3 independently represent hydrogen, optionally substituted (C1-C8) -alkyl, (C2-C4) -alkenyl or a leaving group which can be separated thereon. The invention is characterised in that the oxymorphone compounds of formula (II) or a mixture of compounds of formula (II), which contain at least one corresponding a,?-unsaturated compound is subjected to a hydrogen reaction. The purified noroxymorphone are processed in such a manner that naltrexone or naloxone or a salt of said compounds or a quaternary derivative of said compounds are formed. The invention also relates to pharmaceutical formulations which contain said 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.
N-dealkylation of N-alkyl-14-hydroxymorphinans and derivatives thereof
-
, (2008/06/13)
There is provided a novel, high yield, method of dealkylating N-alkylated 14-hydroxymorphinans and derivatives thereof including, inter alia, oxymorphone and oycodone. There are thus provided, inter alia, more efficient routes for the formation of naloxone, naltrexone, and nalbuphine. In the principal step of the process, the dealkylation using certain oxycarbonyl halides (or haloformates) is carried out on the N-alkyl-14-acyloxy-morphinan which it is desired to dealkylate.
