Synthesis and In Silico Profile Modelling of 6-O-Fluoroalkyl-6-O-desmethyl-diprenorphine Analogues

We present the first preparation of novel 6-O-(fluoroalkyl)-6-O-desmethyl-diprenorphine analogues and 6-O-(tosyloxyalkyl)-6-O-desmethyl-3-O-trityl-diprenorphine type precur-sors for the radiosynthesis of 6-O-([18F]fluoroalkyl)-6-O-desmethyl-diprenorphine radio-tracers for molecular imaging by positron emission tomography (PET). The synthesis se-quence 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 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 se-ries of 6-O-(fluoroalkyl)- and 6-O-(hydroxyalkyl)-6-O-desmethyl-diprenophine derivatives.