Model Studies toward the Total Synthesis of Thebaine by an Intramolecular Cycloaddition Strategy

Abstract

Three model compounds required for an approach to thebaine by intramolecular [4+2] cycloaddition were prepared. In the first two cases the anticipated cycloaddition products were obtained under thermal conditions. Thermolysis of the third, more advanced model compound, afforded products resulting from rearrangements and/or elimination. A study of analogous intra‐ and intermolecular reactions using benzofuran as dienophile and various electron‐poor and electron‐rich dienes (pyridazines, pyranones, Danishefsky diene) was undertaken.

Modular Synthesis of Halogenated Xanthones by a Divergent Coupling Strategy

“…The mixture was extracted with ethyl acetate (3 × 25 mL), the combined organic layers were dried over MgSO 4 , and the solvent was removed under reduced pressure to yield 10 (1.61 g, 8.84 mmol, 99%) as a brown solid. R f : 0.43 (cy/EA 2:1); 1 39,40 Aryl Ether 12. To a solution of ester 10 (1.50 g, 8.23 mmol, 1.00 equiv) in DCM (6 mL) was added Cs 2 CO 3 (8.05 g, 24.7 mmol, 3.00 equiv).…”

Interpol review of controlled substances 2016–2019

“…Opiates: 2016 syntheses of new N-demethyl-N-substituted analogues (propyl, allyl) of 1-fluorocodeine and their 7,8-dihydro derivatives [ 1047 ]; Collison nebulizer as an ionization source for the MS analysis of opiates [ 1048 ]; comparison opiate recovery from acid hydrolysis and enzymatic hydrolysis followed by LC-MS/MS (toxicology focus) [ 1049 ]; synthesis of noroxymorphone from thebaine [ 1050 ]; synthesis of nororipavine and noroxymorphone via N- and O-demethylation of iron tricarbonyl complex of thebaine [ 1051 ]; 2017 investigation of the acid/base behavior of the opium alkaloid thebaine in LC-ESI-MS mobile phase by NMR spectroscopy [ 1052 ]; review of Piritramide [ 1053 ]; model studies toward the total synthesis of Thebaine by an intramolecular [4+2] cycloaddition [ 1054 ]; physico-chemical profiling of semisynthetic opioids characterized by combining pH-potentiometry and deductive methods [ 1055 ]; integrated continuous-flow synthesis of a key oxazolidine intermediate to noroxymorphone from naturally occurring Opioids (oripavine and thebaine) [ 1056 ]; a colorimetric sensor array based on unmodified gold nanoparticles (AuNPs) was developed for the detection and identification of multiple structurally similar opioids including morphine, codeine, oxycodone, noroxycodone, thebaine, tramadol and methadone in aqueous media [ 1057 ]; 2018 Opioids in expensive formulations are being favored over IR morphine both at the dispensing level and in their inclusion in national list of essential medications [ 1058 ]; isolation and determination of Opium Alkaloids by dispersive liquid-liquid microextraction based on solidification of floating organic drop and HPLC-UV detection [ 1059 ]; novel retro-ene reaction via a [4.4.3]propellane intermediate containing a quaternary ammonium linkage [ 1060 ]; review of drug interactions with new synthetic opioids [ 1061 ]; crystal structures of Thebaine 6-O-demethylase in complexes with 2-oxoglutarate and succinate [ 1062 ]; abuse-deterrent Opioids [ 1063 ]; effects of ketamine and norketamine on the attenuation of morphine and oxycodone tolerance [ 1064 ]; review of abuse-deterrent Opioid formulations [ 1065 ]; identification of novel Opioid interferences using High-Resolution Mass Spectrometry [ 1066 ]; changes in consumption of opioid analgesics in Israel 2009 to 2016 focusing on oxycodone and fentanyl formulations [ 1067 ]; trends and characteristics of oxycodone exposures reported to the US Poison Centers, 2011–2017 [ 1068 ]; spatial pattern analysis of 3,396 locations of oxycodone positivity in drivers involved in fatal traffic crashes from the Fatality Analysis Reporting System (FARS) [ 1069 ]; impact of the introduction of tamper-resistant controlled-release (CR) oxycodone in April 2014 in Austra...…”

Altered gene expression and root thebaine production in polyploidized and methyl jasmonate-elicited Papaver bracteatum Lindl

“…Other pharmaceutically important alkaloids produced through this pathway, are morphine, codeine, narcotine, oripavine, papaverine, sanguinarine noscapine, etc. (Koukal et al, 2017). In contrast to opium poppy (Papaver somniferum) where morphine is accumulated as the main alkaloid in the capsules, in P. bracteatum thebaine as the dominant alkaloid is synthetized or accumulated in different amounts in all plant organs, but with the highest concentration in roots and capsules (Sharghi and Lalezari, 1967;Nyman and Bruhn, 1979).…”

“…In contrast to opium poppy (Papaver somniferum) where morphine is accumulated as the main alkaloid in the capsules, in P. bracteatum thebaine as the dominant alkaloid is synthetized or accumulated in different amounts in all plant organs, but with the highest concentration in roots and capsules (Sharghi and Lalezari, 1967;Nyman and Bruhn, 1979). Thebaine serves as a starting material for industrial production of many pharmaceutical drugs, particularly morphine, codeine, semi-synthetic analgesics (oxycodone, oxymorphone, nalbuphine or etorphine) and opioid overdose medications (Koukal et al, 2017). Because of its non-narcotic and non-addictive nature as well as ease of synthetically conversion to other highly-demanded drugs, an increasing international demand exists for thebaine and high-thebaine plant varieties (Shukla et al, 2015).…”