New nepenthone and thevinone derivatives

János Marton, Csaba Simon, Sándor Hosztafi, Zoltán Szabó, A. Márki, A. Borsodi, Sándor Makleit

Research output: Article

15 Citations (Scopus)

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)-phenyI-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-l 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-β-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 δ-opioid receptors were high, but the selectivity was low. Tn two cases (6c and 11d) a μ-opioid receptor specificity was observed.

Original languageEnglish
Pages (from-to)369-382
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume5
Issue number2
DOIs
Publication statusPublished - febr. 1997

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Opioid Receptors
Cyanamide
Derivatives
Cyanogen Bromide
Alkylation
Iodides
Bromides
Alcohols
thevinone
nepenthone
N-propargyl

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

New nepenthone and thevinone derivatives. / Marton, János; Simon, Csaba; Hosztafi, Sándor; Szabó, Zoltán; Márki, A.; Borsodi, A.; Makleit, Sándor.

In: Bioorganic and Medicinal Chemistry, Vol. 5, No. 2, 02.1997, p. 369-382.

Research output: Article

Marton, J, Simon, C, Hosztafi, S, Szabó, Z, Márki, A, Borsodi, A & Makleit, S 1997, 'New nepenthone and thevinone derivatives', Bioorganic and Medicinal Chemistry, vol. 5, no. 2, pp. 369-382. https://doi.org/10.1016/S0968-0896(96)00257-X
Marton, János ; Simon, Csaba ; Hosztafi, Sándor ; Szabó, Zoltán ; Márki, A. ; Borsodi, A. ; Makleit, Sándor. / New nepenthone and thevinone derivatives. In: Bioorganic and Medicinal Chemistry. 1997 ; Vol. 5, No. 2. pp. 369-382.
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