Reactions of morphine derivatives with phenyliodo(III)diacetate (PIDA): synthesis of new morphine analogues.
The reactions of morphine and its derivatives with phenyliodo(III)diacetate (PIDA) have been studied. This methodology has not been introduced to morphine alkaloids, despite the fact that such a strategy would ensure dearomatization of the electrophilic aromatic ring of morphine derivatives leading to nucleophilic ortho-quinoidal structures with potential pharmacological interest. The products, formed in regio- and diastereoselective or diastereospecific reactions, carry mixed-acetal or 1,3-dioxolane moieties. At low concentrations 6a has mu-opioid agonist character but in higher concentrations showed a non receptorial antagonist effect on isolated mouse vas deferens.
Department of Organic Chemistry, Lajos Kossuth University, P.O.Box 20, Debrecen, H-4010, Hungary.
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Garadnay
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Herczegh
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Makleit
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Friedmann
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Riba
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Fürst
D000085:Acetates / Q000737:chemistry*; D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D000085:Acetates; D000701:Analgesics, Opioid; D007462:Iodobenzenes; D009022:Morphine Derivatives; C008857:phenyliodosodiacetate