Synthesen in der Phenanthren‐Reihe, VI. Mitteil.: Synthese des Morphinans

Grewe, Rudolf; Mondon, Albert

doi:10.1002/cber.19480810402

Cited by 104 publications

(24 citation statements)

References 18 publications

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“…The little known pharmacological profiles of the (+)-enantiomers of 6-keto-morphinans suggested that a total synthesis of 12a be conceived, which would allow at the same time the preparation of its optical isomer 12b. The Grewe cyclization of appropriately substituted octahydroisoquinolines, chosen as the key reaction in the synthesis of 12a, b, is greatly facilitated by the presence of an electron withdrawing group on the amine nitrogen (4), and a hydroxy group para-positioned at the point of ring closure (5). It seemed therefore advisable to first attempt the synthesis of 2-hydroxy substituted 6-ketomorphinans, also needed for our SAR studies, and to eliminate the phenolic 2-hydroxy group afterwards.…”

mentioning

confidence: 99%

Synthesis of (−)- and (+)-2-hydroxy-6-keto-N-methylmorphinans, their O-methyl ethers, and 2-deoxy congeners

Schmidhammer¹,

Brossi²

1982

Can. J. Chem.

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HELMUT SCHMIDHAMMER and ARNOLD BROSSI. Can. J. Chem. 60, 3055 (1982).Bischler-Napieralski cyclization of the known phenylacetamide 1, followed by selective ether cleavage of the 3,4-dihydroisoquinoline 2 and sodium borohydride reduction, afforded the tetrahydroisoquinoline 4. Optical resolution of 4 with tartaricacid gave the optical isomers 4a, b , which were converted into the 6-ketomorphinans 9 0 , b and their 0-methyl ethers 100, b by the following reaction sequence: Birch reduction, N-formylation of the dihydro bases, Grewe cyclization, removal of the N-formyl protecting groups, reductive N-methylation, and 0-methylation. The 2-deoxy congeners 1241, b were obtained from 9 a , b by phenyltetrazolylation, and catalytic removal of the heterocyclic ether function. The (-)-enantiomer 1% obtained by this synthesis was identical with material prepared from natural morphine, and exhibited the high antinociceptive potency already reported.HELMUT SCHMIDHAMMER et ARNOLD BROSSI. Can. J. Chem. 60,3055 (1982). La reaction de cyclisation de Bischler-Napieralski de la phenylacetamide 1 suivie du clivage selectif de 1'Cther de la dihydro-3,4 isoquinolCine 2 et de la reduction par le borohydrure de sodium, conduit la tCtrahydroisoquinoleine 4. La rCsolution optique du compose 4 avec I'acide tartrique permet d'obtenir les isomeres optiques 4a ,b que I'on transforme en cCto-6 morphinans 9a,b et en leurs ethers 0-methyliques 10a,b selon les reactions suivantes: la rCduction de Birch, la N-formylation des bases dihydro, la cyclisation de Grewe, le clivage des groupes protecteurs N-formyle, la N-mithylation reductive et 1'0-methylation. On obtient les

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mentioning

confidence: 99%

Synthesis of (−)- and (+)-2-hydroxy-6-keto-N-methylmorphinans, their O-methyl ethers, and 2-deoxy congeners

Schmidhammer¹,

Brossi²

1982

Can. J. Chem.

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“…It is known that metal halides are not active in so-called Lewis acid catalyzed reactions of olefins in the To demonstrate the viability of the N-formyloctahydroabsence of a co-catalyst [25] . Therefore, an explanation for isoquinolines as starting compounds for the synthesis of Nthe activation of the enamide double bond in the presence formylmorphinans we applied the acid-catalyzed cyclization of a Lewis acid might be protonation by a superacid which of the octahydroisoquinolines to the morphinan skeleton, is formed when trace amounts of water or triflic acid are known as the Grewe cyclization [27] . We found that for these present in the reaction mixture.…”

Section: Synthesis Of Morphinansmentioning

confidence: 99%

A Novel Synthesis of Substituted 1-Benzyloctahydroisoquinolines by Acid-Catalyzed Cyclization ofN-[2-(Cyclohex-1-enyl)ethyl]-N-styrylformamides

et al. 1998

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“…N-Methylmorphinan (40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method.…”

Section: Nonnarcotic Antitussivesmentioning

confidence: 99%

Expectorants, Antitussives, and Related Agents

Paul

Dobberstein

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Expectorants enhance the projection of respiratory tract fluid and thus facilitate the mobilization and discharge of bronchial secretions. Stimulant expectorants increase respiratory tract secretion by a direct effect on the bronchial secretory cells, and sedative expectorants act by gastric reflex stimulation. Classes of expectorants discussed include quaiacols, volatile oils, iodides and other inorganic compounds, and miscellaneous natural products. Mucolytics reduce the viscosity of tenacious and purulent mucus, thus facilitating removal. Some agents discussed that chemically depolymerize certain components of mucus include trypsin, other proteolytic enzymes, and cis ‐4‐hydroxymethyl‐2‐iodomethyl‐1,3‐dioxolane. Antitussives control excessive coughing. A brief description of the cough reflex is presented. Centrally active antitussives, both narcotic and nonnarcotic, as well as peripherally active antitussives are presented and discussed.

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Synthesen in der Phenanthren‐Reihe, VI. Mitteil.: Synthese des Morphinans

Cited by 104 publications

References 18 publications

Synthesis of (−)- and (+)-2-hydroxy-6-keto-N-methylmorphinans, their O-methyl ethers, and 2-deoxy congeners

Synthesis of (−)- and (+)-2-hydroxy-6-keto-N-methylmorphinans, their O-methyl ethers, and 2-deoxy congeners

A Novel Synthesis of Substituted 1-Benzyloctahydroisoquinolines by Acid-Catalyzed Cyclization ofN-[2-(Cyclohex-1-enyl)ethyl]-N-styrylformamides

Expectorants, Antitussives, and Related Agents

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