Synthesis and In Silico Profile Modeling of 6-O-Fluoroalkyl-6-O-desmethyl-diprenorphine Analogs
We present the first preparation of novel 6-<i>O</i>-(fluoroalkyl)-6-<i>O</i>-desmethyl-diprenorphine analogs and 6-<i>O</i>-(tosyloxyalkyl)-6-<i>O</i>-desmethyl-3-<i>O</i>-trityl-diprenorphine-type precursors for the radiosynthesis of 6-<i>O</i>-([<sup>18</sup>F]fluoroalkyl)-6-<i>O</i>-desmethyl-diprenorphine radiotracers for molecular imaging by positron emission tomography (PET). The synthesis sequence to the new opioid receptor ligands consists of eleven steps starting from the poppy alkaloid thebaine. The precursor molecules were prepared in a three-step synthesis process from the «<i>Luthra precursor</i>» (TDDPN). We report the complete <sup>1</sup>H- and <sup>13</sup>C-NMR assignment of the new 6-<i>O</i>-(substituted)-6-<i>O</i>-desmethyl-diprenorphine derivatives, as well as the results of docking studies in silico for diverse novel opioid receptor ligands, including a new series of 6-<i>O</i>-(fluoroalkyl)- and 6-<i>O</i>-(hydroxyalkyl)-6-<i>O</i>-desmethyl-diprenorphine derivatives.
Authors
- Frode Willoch (ORCID: https://orcid.org/0000-0002-3328-106X)
- Dávid Gombos (ORCID: https://orcid.org/0009-0001-9435-6002)
- János Marton (ORCID: https://orcid.org/0000-0001-9411-7899)
- Sándor Benyhe (ORCID: https://orcid.org/0000-0002-2235-5334)
- Beate Bauer
- Ferenc Ötvös (ORCID: https://orcid.org/0000-0001-7630-5466)
- Paul Cumming (ORCID: https://orcid.org/0000-0002-0257-9621)
- Bent W. Schoultz
- Alexander Milentyev (ORCID: https://orcid.org/0000-0003-1896-3799)
- Tamás Fehér
Institutions
- Queensland University of Technology (AU)
- University of Oslo (NO)
- University of Szeged (HU)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- University Hospital of Bern (CH)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-09-26
- DOI
- https://doi.org/10.3390/ijms26199427
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00