Stereochemical Studies on Medicinal Agents. 15. Absolute Configurations and Analgetic Potencies of Enantiomeric Diastereomers of 3-Allyl-1-methyl-4-phenyl-4-propionoxypipendine

Kevin H. Bell, Philip S Portoghese

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22 Citations (Scopus)

Abstract

Enantiomeric diastereomers of the title compound la, b were prepared and their absolute configurations determined by chemically relating them to (3R,4S)- and (3S,4R)-1,3-dimethyl-4-phenylpiperidin-4-ol. The analgetic potency of (3R,4S)-la (8a) is 40 times that of morphine and 260 times that of its enanti-omer 10a. Enantiomers of lb (8b and 10b) exhibited no stereoselectivity and possessed a relatively low order of potency (~ 1/12 that of morphine). The fact that this is in marked contrast to the reported high antipodal stereoselectivity for β-prodine suggests that the mode of interaction of lb with analgetic receptors differs from that of β-prodine. Possible reasons for the change of stereoselectivity are discussed.

Original languageEnglish (US)
Pages (from-to)589-591
Number of pages3
JournalJournal of Medicinal Chemistry
Volume16
Issue number6
DOIs
StatePublished - Jun 1 1973

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title = "Stereochemical Studies on Medicinal Agents. 15. Absolute Configurations and Analgetic Potencies of Enantiomeric Diastereomers of 3-Allyl-1-methyl-4-phenyl-4-propionoxypipendine",
abstract = "Enantiomeric diastereomers of the title compound la, b were prepared and their absolute configurations determined by chemically relating them to (3R,4S)- and (3S,4R)-1,3-dimethyl-4-phenylpiperidin-4-ol. The analgetic potency of (3R,4S)-la (8a) is 40 times that of morphine and 260 times that of its enanti-omer 10a. Enantiomers of lb (8b and 10b) exhibited no stereoselectivity and possessed a relatively low order of potency (~ 1/12 that of morphine). The fact that this is in marked contrast to the reported high antipodal stereoselectivity for β-prodine suggests that the mode of interaction of lb with analgetic receptors differs from that of β-prodine. Possible reasons for the change of stereoselectivity are discussed.",
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T1 - Stereochemical Studies on Medicinal Agents. 15. Absolute Configurations and Analgetic Potencies of Enantiomeric Diastereomers of 3-Allyl-1-methyl-4-phenyl-4-propionoxypipendine

AU - Bell, Kevin H.

AU - Portoghese, Philip S

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N2 - Enantiomeric diastereomers of the title compound la, b were prepared and their absolute configurations determined by chemically relating them to (3R,4S)- and (3S,4R)-1,3-dimethyl-4-phenylpiperidin-4-ol. The analgetic potency of (3R,4S)-la (8a) is 40 times that of morphine and 260 times that of its enanti-omer 10a. Enantiomers of lb (8b and 10b) exhibited no stereoselectivity and possessed a relatively low order of potency (~ 1/12 that of morphine). The fact that this is in marked contrast to the reported high antipodal stereoselectivity for β-prodine suggests that the mode of interaction of lb with analgetic receptors differs from that of β-prodine. Possible reasons for the change of stereoselectivity are discussed.

AB - Enantiomeric diastereomers of the title compound la, b were prepared and their absolute configurations determined by chemically relating them to (3R,4S)- and (3S,4R)-1,3-dimethyl-4-phenylpiperidin-4-ol. The analgetic potency of (3R,4S)-la (8a) is 40 times that of morphine and 260 times that of its enanti-omer 10a. Enantiomers of lb (8b and 10b) exhibited no stereoselectivity and possessed a relatively low order of potency (~ 1/12 that of morphine). The fact that this is in marked contrast to the reported high antipodal stereoselectivity for β-prodine suggests that the mode of interaction of lb with analgetic receptors differs from that of β-prodine. Possible reasons for the change of stereoselectivity are discussed.

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