NMR Analysis of a Series of 6, 14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances. Issue 24 (22nd June 2021)

• Record Type: Journal Article
• Authors: Marton, János; Sipos, Attila; Henriksen, Gjermund; Cumming, Paul; Berényi, Sándor; Schmitt, Bettina M.; Szabó, Zoltán
• Is Part Of: ChemistrySelect. Volume 6:Issue 24(2021)
• Page Start: 5994
• Page End: 6005
• Publication Date: 2021-06-22
• Subjects: dihydroetorphine -- 6, 14-ethenomorphinan -- Grignard reaction -- PET precursor -- NMR spectroscopy; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202101597
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: The new semisynthetic oripavine derivative 3‐ O ‐trityl‐6‐ O ‐desmethyl‐dihydroetorphine was synthesized from the poppy alkaloid thebaine in a six‐step procedure. This compound can be applied as precursor for the radiosynthesis of [6‐ O ‐methyl‐ 11 C]‐dihydroetorphine ([ 11 C]DHE). We present a detailed description of 1 H and 13 C NMR data of reference standards and precursors for [6‐ O ‐methyl‐ 11 C]‐ and [6‐ O ‐(2‐[ 18 F]fluoroethyl]orvinols. This includes the complete assignment for 19 oripavine derivatives examined in 1D and 2D NMR experiments. We also investigated the molecular basis for regioselectivity of fluoroalkylation of 3‐ O ‐trityl‐6‐ O ‐desmethyl‐phenethyl‐orvinol (TDPEO) using computational methods. Abstract : This paper presents the synthesis of a new precursor, 3‐ O ‐trityl‐6‐ O ‐desmethyl‐dihydroetorphine (TDDHE), for the radiosynthesis of [6‐ O ‐methyl‐ 11 C]‐dihydroetorphine ([ 11 C]DHE) starting from the poppy alkaloid thebaine. Detailed NMR analysis of nineteen oripavine derivatives relevant for the PET imaging of opioid receptors applying 1D ( 1 H‐, 13 C‐, 19 F) and 2D ( 1 H‐ 1 H‐COSY, 1 H‐ 13 C‐HMQC, 1 H‐ 13 C‐HMBC) techniques was presented. The background of the selective alkylation of 3‐ O ‐trityl‐6‐ O ‐desmethyl‐orvinol derivatives was studied using computational methods.