Stereochemical Studies on Medicinal Agents. VII. Absolute Stereochemistry of Methadol Isomers and the Role of the 6-Methyl Group in Analgetic Activity

Philip S Portoghese, D. A. Williams

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Abstract

The stereochemistry of optically active α- and β-methadol has been deduced by the asymmetric synthetic procedure of Prelog. The apparent dissociation constants of the title compounds, when compared with those of methadone and 3-deoxymethadone, suggest the absence of substantial intramolecular H bonding in aqueous medium. Nmr and ir studies point to the presence of strong intramolecular H bonds in nonpolar media, with the β isomer being more strongly internally associated. Possible preferred conformations which are consistent with the spectral data are depicted. The (6R), (6S), and (6R) receptor stereoselectivities for methadone, α-methadol, and acetyl-α-methadol, respectively, have been rationalized in terms of differing modes of interaction.

Original languageEnglish (US)
Pages (from-to)839-844
Number of pages6
JournalJournal of Medicinal Chemistry
Volume12
Issue number5
DOIs
StatePublished - Sep 1 1969

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Methadyl Acetate
Methadone

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abstract = "The stereochemistry of optically active α- and β-methadol has been deduced by the asymmetric synthetic procedure of Prelog. The apparent dissociation constants of the title compounds, when compared with those of methadone and 3-deoxymethadone, suggest the absence of substantial intramolecular H bonding in aqueous medium. Nmr and ir studies point to the presence of strong intramolecular H bonds in nonpolar media, with the β isomer being more strongly internally associated. Possible preferred conformations which are consistent with the spectral data are depicted. The (6R), (6S), and (6R) receptor stereoselectivities for methadone, α-methadol, and acetyl-α-methadol, respectively, have been rationalized in terms of differing modes of interaction.",
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T1 - Stereochemical Studies on Medicinal Agents. VII. Absolute Stereochemistry of Methadol Isomers and the Role of the 6-Methyl Group in Analgetic Activity

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AU - Williams, D. A.

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N2 - The stereochemistry of optically active α- and β-methadol has been deduced by the asymmetric synthetic procedure of Prelog. The apparent dissociation constants of the title compounds, when compared with those of methadone and 3-deoxymethadone, suggest the absence of substantial intramolecular H bonding in aqueous medium. Nmr and ir studies point to the presence of strong intramolecular H bonds in nonpolar media, with the β isomer being more strongly internally associated. Possible preferred conformations which are consistent with the spectral data are depicted. The (6R), (6S), and (6R) receptor stereoselectivities for methadone, α-methadol, and acetyl-α-methadol, respectively, have been rationalized in terms of differing modes of interaction.

AB - The stereochemistry of optically active α- and β-methadol has been deduced by the asymmetric synthetic procedure of Prelog. The apparent dissociation constants of the title compounds, when compared with those of methadone and 3-deoxymethadone, suggest the absence of substantial intramolecular H bonding in aqueous medium. Nmr and ir studies point to the presence of strong intramolecular H bonds in nonpolar media, with the β isomer being more strongly internally associated. Possible preferred conformations which are consistent with the spectral data are depicted. The (6R), (6S), and (6R) receptor stereoselectivities for methadone, α-methadol, and acetyl-α-methadol, respectively, have been rationalized in terms of differing modes of interaction.

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