cas 16590-41-3, Naltrexone | Articles data

Articles about 16590-41-3Total 45 be found

Article title
Article abstract
Author
Journal number and time
Download

General method of synthesis for naloxone, naltrexone, nalbuphone, and nalbuphine by the reaction of grignard reagents with an oxazolidine derived from oxymorphone
The N-oxide of O-acyloxymorphone, when treated with the Burgess reagent, provides the corresponding oxazolidine in a one-pot sequence and in excellent yield. The oxazolidine derived from oxymorphone, temporarily protected at O-3 and C-6, reacts with Grignard reagents to provide directly N-allyl, N-cyclopropylmethyl, and N-cyclobutylmethyl derivatives that are further converted to the title compounds, namely naltrexone, naloxone, nalbuphone, and nalbuphine in excellent yields. Each of these medicinal agents is obtained from the oxazolidine in a one-pot sequence. Complete spectral and experimental data are provided for all compounds. Copyright
Endoma-Arias, Mary Ann A.,Cox, D. Phillip,Hudlicky, Tomas
p. 1869 - 1873
(2013)
Read Online

Synthesis, characterization and evaluation of computationally designed nanoparticles of molecular imprinted polymers as drug delivery systems
The aim of the present study was to prepare nanoparticles of molecular imprinted polymers (MIPs) with high loading capacity for naltrexone as template drug. To achieve this goal, a computational protocol was employed to select the most appropriate monomer for MIP preparation. Density functional theory (DFT) method at the B3LYP level of theory in conjugate with the 6-31+G(d) basis set was used to evaluate the extent of interaction between naltrexone and a small library of frequently used vinylic monomers. The results revealed that acrylic acid (AA) and methacrylic acid (MAA) can be considered as suitable monomers. To select the best monomer, two MIPs with AA and MAA monomer were synthesized and their loading capacity, selectivity and release profile were evaluated. The experimental results showed that the MIPs synthesized using AA (MIP-AA) exhibited a surprisingly high loading capacity to naltrexone (75 mg of drug/g of MIP) compared to MIP-MAA (34 mg of drug/g of MIP). In vitro release dynamics of the drug from MIPs was also investigated and modeled. It was found that non-Fickian-type diffusion mechanism was responsible for drug release. The results can lead to the conclusion that MIPs designed by computational approach can be considered as promising candidates for drug delivery systems.
Rostamizadeh,Vahedpour,Bozorgi
p. 67 - 75
(2012)
Read Online

Synthesis of noroxymorphone by n-demethylation/ intramolecular acylation of oxymorphone catalyzed by iron(II) chloride
Oxymorphone was converted to its 3,14-diacetate and subjected to Fe(II)/t-BuOOH-catalyzed N-demethylation that occurred with concomitant acyl migration from the C-14 hydroxyl to the N-17 nitrogen. The resulting diacetyl compound was hydrolyzed in dilute s
Endoma-Arias, Mary Ann A.,Machara, Ales,Cox, D. Phillip,Hudlicky, Tomas
p. 824 - 832
(2016)
Read Online

Investigation of structure, vibrational and NMR spectra of oxycodone and naltrexone: A combined experimental and theoretical study
In this work, two important opioid antagonists, naltrexone and oxycodone, were prepared from thebaine and were characterized by IR, 1H NMR and 13C NMR spectroscopy. Moreover, computational NMR and IR parameters were obtained using density functional theory (DFT) at B3LYP/6-311++G* * level of theory. Complete NMR and vibrational assignment were carried out using the observed and calculated spectra. The IR frequencies and NMR chemical shifts, determined experimentally, were compared with those obtained theoretically from DFT calculations, showed good agreements. The RMS errors observed between experimental and calculated data for the IR absorptions are 85 and 105 cm-1, for the 1H NMR peaks are 0.87 and 0.17 ppm and for those of 13C NMR are 5.6 and 5.3 ppm, respectively for naltrexone and oxycodone.
Tavakol, Hossein,Esfandyari, Maryam,Taheri, Salman,Heydari, Akbar
p. 574 - 582
(2011)
Read Online

Direct synthesis of naltrexone by palladium-catalyzed N-demethylation/ acylation of oxymorphone: The benefit of C-H activation and the intramolecular acyl transfer from C-14 hydroxy
Oxymorphone was converted to naltrexone in three steps by palladium-catalyzed oxidative N-demethylation and intramolecular acyl transfer from C-14 hydroxy to N-17. VitrideTM reduction of N-acylamide to N-alkylamine proceeded with concomitant re
MacHara, Ales,Cox, D.Phillip,Hudlicky, Tomas
p. 2713 - 2718
(2012)
Read Online

Unexpected N-demethylation of oxymorphone and oxycodone N-oxides mediated by the burgess reagent: Direct synthesis of naltrexone, naloxone, and other antagonists from oxymorphone
N-Oxides derived from oxycodone and O-acyloxymorphone were treated with the Burgess reagent to provide the corresponding oxazolidines in excellent yields. Oxazolidines derived from Oacyloxymorphone were further hydrolyzed to noroxymorphone, whose alkylation furnished naltrexone, naloxone, and nalbuphone, which can be converted to nalbuphine, the mixed agonist-antagonist analgesic. The entire sequence from oxymorphone to the various antagonists was reduced to three one-pot operations, proceeding in excellent overall yields. In addition, quaternary salts of the oxazolidines with allyl or cyclopropylmethyl groups in fixed equatorial configurations were synthesized. Complete spectral and experimental data are provided for all compounds.
Werner, Lukas,Wernerova, Martina,MacHara, Ales,Endoma-Arias, Mary Ann,Duchek, Jan,Adams, David R.,Cox, D. Phillip,Hudlicky, Tomas
p. 2706 - 2712
(2012)
Read Online

Asymmetric synthesis of (-)-naltrexone
(-)-Naltrexone, an opioid antagonist used extensively for the management of drug abuse, is derived from naturally occurring opioids. Herein, we report the first asymmetric synthesis of (-)-naltrexone that does not proceed through thebaine. The synthesis starts with simple, achiral precursors with catalytic enantioselective Sharpless dihydroxylation employed to introduce the stereogenic centers. A Rh(i)-catalyzed C-H alkenylation and torquoselective electrocyclization cascade provides the hexahydro isoquinoline bicyclic framework that serves as the precursor to the morphinan core. The acidic conditions used for Grewe cyclization not only provide the morphinan framework, but also cause a hydride shift resulting in the introduction of the C-6 oxo functionality present in (-)-naltrexone. The C-14 hydroxyl group is installed by an efficient two-step sequence of Pd-mediated ketone to enone dehydrogenation followed by C-H allylic oxidation using Cu(ii) and O2, a method that has not previously been reported either for the synthesis or semi-synthesis of opioids. The longest linear sequence is 17 steps, and because the stereogenic centers in the product rely on Sharpless asymmetric dihydroxylation, the route could be used to access either enantiomer of the natural product, which have disparate biological activities. The route also may be applicable to the preparation of opioid derivatives that could not be easily prepared from the more fully elaborated and densely functionalized opioid natural products that have traditionally served as the starting inputs.
Dongbang, Sun,Pedersen, Blaine,Ellman, Jonathan A.
p. 535 - 541
(2019/01/10)

PROCESS FOR THE PREPARATION OF MORPHINANE COMPOUNDS
The invention describes the process of catalytic O-demethylation of 3-methoxy-morphinane compounds using boron tribromide. Addition of catalysts reduces the reaction time, improves reacting the substrate to give the product in very good purity and yield. The said approach can be used, for example, for the preparation of oxymorphone, naltrexone, naloxone and nalbuphine from their respective O-methyl derivatives.
-
Page/Page column 9

(2019/01/21)

Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects
Structure-activity relationship studies of several morphinan derivatives were conducted to obtain dual antagonists for μ- and δ-opioid receptors. We discovered peripherally restricted dual antagonists for μ/δ-opioid receptors as a new chemotype with a morphinan scaffold, which are orally available and do not easily pass the blood–brain barrier. As we expected, some of these compounds inhibit opioid-induced constipation and emesis/vomiting with limited potential to interfere the analgesic effects of morphine. Among them, naldemedine was selected as a potential drug candidate.
Inagaki, Masanao,Kume, Masaharu,Tamura, Yoshinori,Hara, Shinichiro,Goto, Yoshihisa,Haga, Nobuhiro,Hasegawa, Tsuyoshi,Nakamura, Takashi,Koike, Katsumi,Oonishi, Shuuichi,Kanemasa, Toshiyuki,Kai, Hiroyuki
p. 73 - 77
(2018/11/23)

METHOD FOR ISOLATION AND PURIFICATION OF NALTREXONE
The invention describes a method for purification of naltrexone base from reaction mixtures concentrated by evaporation and/ or from mixtures containing naltrexone in the presence of other organic or inorganic substances by trituration and/or extraction and crystallization from cyclopentyl methyl ether (CPME), optionally from a mixture of cyclopentyl methyl ether and another organic solvent. Naltrexone of high purity is obtained by this method and can be used in a parenteral dosage form.
-
Page/Page column 7

(2018/04/27)

PROCESS FOR OBTAINING 3,14-DIACETYLOXYMORPHONE FROM ORIPAVINE
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.
-
Page/Page column 48; 49

(2018/01/17)

REDUCTION OF ALPHA, BETA-UNSATURATED KETONE LEVELS IN MORPHINAN DERIVATIVE COMPOSITIONS
The disclosure relates to processes for reducing the amount of a compound of formula (I) or a salt or a solvate thereof present in a composition comprising compounds of formulae (I) and (II) or a salt or a solvate thereof.
-
Page/Page column 00583; 00584; 00585

(2016/04/26)

PROCESS FOR THE PREPARATION OF OPIOID COMPOUNDS
The present invention is directed to a process for the preparation of opioid compounds such as buprenorphine, naltrexone, naloxone, nalbuphone, nalbuphine, and the like.
-
Paragraph 0186; 0187

(2015/11/27)

PROCESS FOR THE PREPARATION OF OPIOID COMPOUNDS
The present invention is directed to a process for the preparation of opioid compounds such as buprenorphine, naltrexone, naloxone, nalbuphone, nalbuphine, and the like.
-
Page/Page column 45-47

(2015/11/27)

Synthesis of Naltrexone and (R)-Methylnaltrexone from Oripavine via Direct Oxidation of Its Quaternary Salts
(R)-Methylnaltrexone and naltrexone were each prepared in four steps from oripavine in practical yields. The procedure involved quaternization of oripavine with cyclopropylmethyl halides, singlet oxygen oxidation of the quaternary salts, and the reduction of endo peraoxides to 14-hydroxyketone functionalities. (R)-Methylnaltrexone was prepared from the corresponding R-diastereomer of the oripavine salt. All diastereomeric mixtures of the quaternary salts were subjected to N-demethylation with sodium thiolate to yield cyclopropyl methylnororipavine, which was converted into naltrexone by peracid oxidation and hydrogenation according to established procedures.
Machara, Ales,Werner, Lukas,Leisch, Hannes,Carroll, Robert J.,Adams, David R.,Haque, D. Mohammad,Cox, D. Phillip,Hudlicky, Tomas
p. 2101 - 2108
(2015/09/15)

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CHRONIC PAIN
The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II, and methods for treating chronic pain in a disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of acute pain (such as post-operative pain), palliative care to alleviate the severe, chronic, disabling pain of terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis, non-malignant chronic pain, chemotherapy induced pain, musculoskeletal pain, sciatica, radiculopathy pain, migraine, neuropathic pain, post herpetic neuralgia, neuralgia pain, multiple sclerosis, multiple sclerosis, restless legs syndrome (RLS), cluster headache, depression, fibromyalgia and amyotrophic lateral sclerosis (ALS).
-
Paragraph 0145

(2015/05/26)

CONVENIENT PREPARATION OF N-SUBSTITUTED MORPHINAN-6-OLS FROM MORPHINAN-6-ONES
Described herein are methods of preparing 6-hydroxy N-alkyl morphinan-6-ols from morphinan-6-ones, as illustrated below: wherein the variables R1, R2, R3, R10, R11, R14, and are as defined herein and wherein the reactions occur in a one-pot procedure using a boron based reducing agent.
-
Paragraph 0098

(2015/05/13)

METHOD FOR THE MANUFACTURING OF NALTREXONE
The present invention relates to a new process for producing naltrexone [17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-morphinan-6-one] from noroxymorphone [4,5-α-epoxy-3,14-dihydroxy-morphinan-6-one] by alkylation with a cyclopropylmethyl halide.
-
Paragraph 0082-0088

(2014/06/23)

METHOD FOR THE MANUFACTURING OF NALTREXONE
The present invention relates to a new process for producing naltrexone [17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-morphinan-6-one] from noroxymorphone [4,5- α-epoxy-3,14-dihydroxy-morphinan-6-one] by alkylation with a cyclopropylmethyl halide.
-
Page/Page column 11

(2013/11/19)

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CHRONIC PAIN
The invention relates to the compounds of formula (I) and formula (II) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula 1 or formula II, and methods for treating chronic pain in a disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of acute pain (such as post-operative pain), palliative care to alleviate the severe., chronic, disabling pain of terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis, non-malignant chronic pain, chemotherapy induced pain, musculoskeletal pain, sciatica, radiculopathy pain, migraine, neuropathic pain, post herpetic neuralgia, neuralgia pain, multiple sclerosis, multiple sclerosis, restless legs syndrome (R.l,S), cluster headache, depression, fibromyalgia and amyotrophic lateral sclerosis (A.LS).
-
Paragraph 0097; 00104; 00105

(2013/12/03)

PROCESS FOR THE PREPARATION OF MORPHINE ANALOGS VIA THE REACTION OF ORGANOMETALLIC REAGENTS WITH AN OXAZOLIDINE DERIVED FROM MORPHINANS
The oxazolidine derived from the reaction of oxymorphone with the Burgess reagent, temporariiy protected at 0-3 and C-6, reacts with Grignard or other suitable metallic or organometallic reagents to directly provide, for example, A/-allyl, A/-methylcyclopropyl and /V-methylcyclobutyl derivatives that are further converted into naltrexone, naloxone, nalbuphone and nalbuphine in excellent yields. These morphine analogs can be prepared from the oxazolidine in a one- pot synthesis.
-
Paragraph 0088

(2013/08/15)

METHOD FOR THE MANUFACTURING OF NALTREXONE
The present invention relates to an improved process for producing naltrexone[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-morphinan-6-one] from noroxymorphone[4,5-α-epoxy-3,14-dihydroxy-morphinan-6-one] by alkylation with a cyclopropylmethyl halide.
-
Page/Page column 6

(2012/05/20)

Processes and Intermediates in the Preparation of Morphine Analogs via N-Demethylation of N-Oxides Using Cyclodehydration Reagents
A high-yielding method for the N-demethylation of oxycodone- and oxymorphone-N-oxides by the reaction of these compounds with cyclodehydration reagents has been performed. This method has been utilized to improve the synthesis of various morphine analogs, such as naltrexone, nalbuphone and naloxone.
-
Page/Page column 17

(2012/11/13)

PROCESS FOR THE PREPARATION OF MORPHINE ANALOGS VIA METAL CATALYZED N-DEMETHYLATION/FUNCTIONALIZATION AND INTRAMOLECULAR GROUP TRANSFER
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.
-
Page/Page column 13

(2012/11/13)

N-Alkylation of Opiates
The present invention provides an efficient process for preparing N-alkylated opiates. In particular, processes are provided for using a chloride-containing alkylating agent and a bromide or iodide salt to alkylate the corresponding nor-opiate.
-
Page/Page column 9

(2011/11/12)

PERIPHERAL OPIOID AGONISTS AND PERIPHERAL OPIOID ANTAGONISTS
The present disclosure provides compositions, and their methods of use, where the compositions comprise a ketone-modified opioid drug, wherein the drug comprises a ketone-modified opioid and a substituent on the opioid that mediates retention of the drug in the peripheral nervous system as opposed to the central nervous system following ingestion by a subject.
-
Page/Page column 71

(2011/11/06)

Processes for the synthesis of tertiary amines
The invention provides processes for the preparation of morphinans having a tertiary amine. In particular, the present invention provides processes for the formation of tertiary amine alkaloids by direct N-alkylation of secondary amine alkaloids, the processes co-mediated by an alkylating agent and a protic solvent or a mixture of a protic solvent and an aprotic solvent.
-
Page/Page column 11

(2010/04/25)

METHOD FOR PRODUCING N-METHYLNALTREXONE BROMIDE
Process for the preparation of N-methylnaltrexone bromide, wherein a compound of the general formula (I): wherein X? represents an anion other than the bromide anion, and R represents hydrogen or a leaving group, is dissolved or dispersed in a suitable polar solvent, the solution or dispersion is mixed with a compound containing bromide anions, and the resulting reaction mixture is stirred until N-methylnaltrexone bromide has formed and crystallised, wherein, in the case where R represents a leaving group, that group is removed during or after the reaction.
-
Page/Page column 4

(2010/07/08)

PROCESSES FOR THE PREPARATION OF MORPHINANE AND MORPHINONE COMPOUNDS
The present application describes processes for the synthesis of morphinane and morphinone compounds, useful as pharmaceutical agents. Also included are novel intermediates useful in the preparation of these compounds. The process comprises quaternization of oripavine to provide a mixture of the R- and S-isomeric (at the nitrogen) quaternary salts. The R-isomer is readily isolated and converted to various N-(R)-morphinane and N-(S)-morphinone compounds. The R-isomer, S-isomer or a mixture of R- and S-isomers may be demethylated and converted to various morphinane and morphinone compounds.
-
Page/Page column 66

(2010/11/05)

Novel 3-O-pegylated carboxylate and 3-O-pegylated carbamate prodrugs of naltrexone for microneedle-enhanced transdermal delivery
A small library of novel 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were synthesized. The goal behind the design of these prodrugs was to investigate their potential for microneedle-enhanced transdermal delivery. All the synthesized 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were found to have adequate stability in a transdermal formulation and improved apparent solubility compared to naltrexone. Viscosity effects were postulated to be responsible for the observed non-linearity in the flux-concentration profile of these prodrugs.
Yerramreddy, Thirupathi Reddy,Milewski, Mikolaj,Penthala, Narsimha Reddy,Stinchcomb, Audra L.,Crooks, Peter A.
scheme or table
p. 3280 - 3283
(2010/08/19)

PERIPHERAL OPIOID RECEPTOR ANTAGONISTS AND USES THEREOF
The present invention provides a compound of formula I: wherein X-, R1, and R2 are as defined herein, and compositions thereof. The compounds are peripheral opioid receptors.
-
Page/Page column 41-43

(2010/04/27)

Processes for the selective amination of ketomorphinans
The present invention is generally directed to a process for the preparation of a ketomorphinan comprising maintaining a ketone group as unprotected and performing reductive amination using a hydrogen source and a catalyst.
-
Page/Page column 12

(2010/04/25)

Process for the Reductive Alkylation of Normorphinans
The invention provides a process for the N-alkylation of normorphinan compounds to produce N-alkylated morphinan compounds. In particular, the process relates to the alkylation of a normorphinan compound by a carboxaldehyde in the presence of a reducing agent to form an N-alkylated morphinan.
-
Page/Page column 7

(2010/08/22)

AN IMPROVED PROCESS FOR THE PREPARATION OF MORPHINANE ANALOGUES
The present invention relates to an improved process for preparing morphinane analogues of formula (1) wherein the substituents R1, R2, R2a, R3, R4, R5 and Y have the meanings as defined in the specifications.
-
(2009/10/30)

PREPARATION OF N-ALKYLATED OPIATES BY REDUCTIVE AMINATION
The present invention is directed to the reduction of an N-imine moiety or a hemiaminal moiety of a morphinan in the presence of a ruthenium, rhodium, or iridium asymmetric catalyst and a hydrogen source.
-
Page/Page column 17

(2009/03/07)

(S)-N-Stereoisomers of 7,8-Saturated-4,5-Epoxy-Morphinanium Analogs
Novel (S)-N-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the (S)-N-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs and methods for their pharmaceutical uses are also disclosed. Such analogs are disclosed as being useful in treating, among varying conditions, hypermotility of the gastrointestinal tract.
-
Page/Page column 31-32

(2008/12/08)

PROCESS FOR PREPARING N-ALKYLNALTREXONE HALIDES
The invention relates to a novel process for preparing N-methylnaltrexone bromide, comprising at least the steps consisting in: (i) reacting N-methylnaltrexone methyl sulfate in aqueous solution with an alkaline agent chosen from the group constituted by sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, cesium carbonate, strontium carbonate and mixtures thereof, for a pH of the aqueous reaction medium of between 7 and 10, and then in(ii) reacting the product thus obtained with hydrobromic acid, which is added for a pH of the aqueous reaction medium of between 0.5 and 5, in order thus to obtain the N-methylnaltrexone bromide.
-
Page/Page column 1; 4

(2008/12/08)

Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6β-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents
A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was to design and synthesize codrugs for simultaneous treatment of alcohol abuse and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was determined. These codrugs were generally less crystalline when compared to NTX, or NTXOL, as indicated by their lower melting points, and were expected to be more lipid-soluble. Also, the calculated c logP values were found to be higher for the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of the codrugs provided good evidence that they could be efficiently converted to the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to be cleaved enzymatically in vivo to generate the parent drugs, and are considered to be potential candidates for simultaneous treatment of alcohol abuse and tobacco dependence.
Hamad, Mohamed O.,Kiptoo, Paul K.,Stinchcomb, Audra L.,Crooks, Peter A.
p. 7051 - 7061
(2007/10/03)

PREPARATION OF OPIATE ANALGESICS BY REDUCTIVE ALKYLATION
A process for preparing a compound of formula (A), (B) or (C): wherein P is H, CH3 or a hydroxyl protecting group; X is O, a protected ketone, OH, a protected hydroxyl group or H; Y is OH, a protected hydroxyl group or H; W is C(CH3)2OH, C(CH3)(C(CH3)3)OH or COCH3; Z is C2-C10 alkyl or C2-C10 arylalkyl; and ′ is a. single bond or a double bond, is disclosed. The process is a reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.
-
Page/Page column 6-7

(2008/06/13)

Preparation of 14-hydroxynormorphinones from normorphinone dienol acylates
The invention provides processes for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. The invention also provides certain novel intermediates.
-
(2008/06/13)

L-Selectride as a general reagent for the O-demethylation and N- decarbomethoxylation of opium alkaloids and derivatives
L-Selectride was shown to be an efficient and general O-demethylating agent for the opium alkaloids and their derivatives and also an efficient reagent for the cleavage of methyl carbamates, thus offering a convenient method for the N-demethylation of opioids. Further, it was shown that by choice of reaction conditions it is possible to achieve both N- decarbomethoxylation and O-demethylation in one pot, or only render N- decarbomethoxylation in high yield without accompanying O-demethylation.
Coop,Janetka,Lewis,Rice
p. 4392 - 4396
(2007/10/03)

KAPPA OPIOID RECEPTOR ANTAGONISTS
Compounds of the formula: STR1 are provided, which are selective kappa opioid receptor antagonists, wherein R 1 is (C 1-C 5) alkyl, C 3-C 6 (cycloalkyl)alkyl, C 5-C 7 (cycloalkenyl) alkyl, (C 6-C 12)aryl, (C 6-C 12)aralkyl, trans (C 4-C. sub.5) alkenyl, allyl or furan-2-ylalkyl; R 2 is H, OH or O 2 C(C 1-C 5)alkyl; R 3 is H, (C 6-C 10)aralkyl, (C. sub.1-C 5)alkyl or (C 1-C 5)alkylCO; X is O, S or NY, wherein Y is H or (C 1-C 5)alkyl; R 4 is CH 2 (methylene) or C=O (carbonyl), R 5 is CH 2, C=O or C=NH (imino) and R 6 is (C 1-C 4)alkyl or NH(C 1-C. sub.4)alkyl, optionally substituted by a non-terminal (C 1-C 2) alkyl group or by N(R 7) (R 8) wherein R 7 and R 8 are individually H or (C 1-C 3) alkyl, with the proviso that one of R 4 or R 5 is CH 2, and the pharmaceutically acceptable salts thereof.
-
(2008/06/13)

O-Demethylation of opioid derivatives with methane sulfonic acid/methionine: Application to the synthesis of naloxone and analogues
Naloxone 2 was obtained by demethylation of N-allylnoroxycodone 1 with methane sulfonic acid/methionine. This reagent is an excellent substitute for boron tribromide. It was used for the synthesis of analogous derivatives with variable results.
Andre,Dormoy,Heymes
p. 2313 - 2327
(2007/10/02)

SYNTHESIS OF DIHYDROMORPHINONES FROM DIHYDROCODEINONES
-
Kalinin, V. N.,Kobel'kova, N. I.,Bodrov, D. E.
p. 407 - 408
(2007/10/02)

N-dealkylation of N-alkyl-14-hydroxymorphinans and derivatives thereof
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.
-
(2008/06/13)