title: New nepenthone and thevinone derivatives.
abstract: The diastereoselective reaction of thevinone (2a) and nepenthone (2c) and their dihydro derivatives (2b and d) with Grignard reagents afforded new N-substituted (20S)- and (20R)-phenyl-6,14-ethenomorphinan derivatives (6a-y). The Grignard reaction of the N-substituted-N-demethyl derivatives 4a-f and 4m-r with methylmagnesium iodide resulted in the (20R)-phenyl tertiary alcohols 5a-f and 5m-r, respectively, but the conversion of 4g-1 and that of the N-substituted-dihydrothevinone derivatives with phenylmagnesium bromide afforded the (20S)-phenyl derivatives 5g-l and 5s-y, respectively. The N-cyclopropylmethyl-, N-beta-phenylethyl-, and N-propyl derivatives were prepared by the 3-O-demethylation of compounds 5. For the synthesis of the N-allyl-, N-dimethylallyl-, and N-propargyl compounds 2a-d were reacted with the corresponding Grignard reagent, and treatment of the products with cyanogen bromide gave the cyanamides 8a-d. These latter compounds were transformed into 10a, b,d, whose alkylation led to the target derivatives 6d-f, j-l, p-r, and w-y. The biochemical investigation of these substances showed that the affinities to the delta-opioid receptors were high, but the selectivity was low. In two cases (6c and 11d) a mu-opioid receptor specificity was observed.
authors.affiliation: Alkaloida Chemical Company Ltd., Tiszavasvári, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Marton
authors.forename: C
authors.initials: C
authors.lastname: Simon
authors.forename: S
authors.initials: S
authors.lastname: Hosztafi
authors.forename: Z
authors.initials: Z
authors.lastname: Szabó
authors.forename: A
authors.initials: A
authors.lastname: Márki
authors.forename: A
authors.initials: A
authors.lastname: Borsodi
authors.forename: S
authors.initials: S
authors.lastname: Makleit
mesh_terms: D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009019:Morphinans / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism
chemical_list: D009019:Morphinans; C105913:thevinone; C105912:nepenthone