Synthesis and In Silico Profile Modeling of 6-O-Fluoroalkyl-6-O-desmethyl-diprenorphine Analogs
János Marton, Dávid Gombos, Paul Cumming, Tamás Fehér, Alexander Milentyev, Beate Bauer, Frode Willoch, Bent Wilhelm Schoultz, Sándor Benyhe, Ferenc Ötvös
TL;DR
Scientists synthesized new diprenorphine analogs for PET imaging and studied their structure and opioid receptor interactions.
Contribution
The first synthesis of 6-O-fluoroalkyl-6-O-desmethyl-diprenorphine analogs and their in silico docking profiles for opioid receptors.
Findings
Eleven-step synthesis of novel diprenorphine analogs from thebaine was successfully achieved.
Complete NMR assignments were reported for new 6-O-substituted derivatives.
In silico docking studies revealed potential opioid receptor ligand interactions for new fluoroalkyl and hydroxyalkyl derivatives.
Abstract
We present the first preparation of novel 6-O-(fluoroalkyl)-6-O-desmethyl-diprenorphine analogs and 6-O-(tosyloxyalkyl)-6-O-desmethyl-3-O-trityl-diprenorphine-type precursors for the radiosynthesis of 6-O-([18F]fluoroalkyl)-6-O-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 «Luthra precursor» (TDDPN). We report the complete 1H- and 13C-NMR assignment of the new 6-O-(substituted)-6-O-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-O-(fluoroalkyl)- and 6-O-(hydroxyalkyl)-6-O-desmethyl-diprenorphine derivatives.
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Taxonomy
TopicsFluorine in Organic Chemistry · Forensic Toxicology and Drug Analysis · Cancer Treatment and Pharmacology