NMR Spectra and Stereochemistry of some 7‐Substituted 6,14‐Bridged Thebaine Derivatives

Uff, B. C.; Mallard, Angela S.; Davis, John A.; Henson, Ray

doi:10.1002/mrc.1260230610

Cited by 24 publications

(5 citation statements)

References 15 publications

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“…1D ( 1 H‐, 13 C‐, 19 F), and 2D NMR techniques were used for the identification and characterization of the prepared compounds. 1 H‐ and 13 C‐NMR assignments were obtained from 1 H‐ 1 H correlations spectroscopy (COSY), 2D heteronuclear 1 H‐ 13 C multiple quantum correlations experiments (HMQC) and heteronuclear multiple bond correlations (HMBC), which was facilitated by previously published NMR studies on various Bentley‐type compounds [48–55] . Stereochemical nomenclature and numbering of the orvinols are depicted in Figure 6.…”

Section: Resultsmentioning

confidence: 99%

“…1 H-and 13 C-NMR assignments were obtained from 1 H-1 H correlations spectroscopy (COSY), 2D heteronuclear 1 H- 13 C multiple quantum correlations experiments (HMQC) and heteronuclear multiple bond correlations (HMBC), which was facilitated by previously published NMR studies on various Bentleytype compounds. [48][49][50][51][52][53][54][55] Stereochemical nomenclature and numbering of the orvinols are depicted in Figure 6. Complete assignments of 1 H-and 13 C-NMR spectra of the synthesized derivatives are given in Supporting Information (Table S2-S5, page [13][14][15][16].…”

Section: Nmr Analysismentioning

confidence: 99%

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NMR Analysis of a Series of 6,14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances**

et al. 2021

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The new semisynthetic oripavine derivative 3-O-trityl-6-Odesmethyl-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.

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Section: Resultsmentioning

confidence: 99%

Section: Nmr Analysismentioning

confidence: 99%

NMR Analysis of a Series of 6,14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances**

et al. 2021

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“…1D ( 1 H-, 13 C-, 19 F), 2D NMR techniques and ESI-MS were used for the identification of the prepared compounds. 1 H and 13 C-NMR assignments were obtained from 1 H- 1 H correlation spectroscopy (COSY), 2D heteronuclear 1 H- 13 C multiple quantum correlations experiments (HMQC) and heteronuclear multiple bond correlations (HMBC) and facilitated by previously published NMR studies on various 6,14-ethenomorphinan derivatives [ 13 , 19 , 20 , 21 , 22 ]. NMR spectral assignments are presented in the Experimental Section.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of an 18F-Labeled Version of Phenylethyl Orvinol ([18F]FE-PEO) for PET-Imaging of Opioid Receptors

Marton

Henriksen

2012

Molecules

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The semisynthetic oripavine derivative phenethyl orvinol (PEO), a full agonist at opioid receptors (OR), is an attractive structural motif for developing 18F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference compound 6-O-(2-fluoroethyl)-6-O-desmethylphenylethyl orvinol (FE-PEO) was obtained via two separate reaction routes. A three-step synthesis was developed for the preparation of a tosyloxyethyl precursor (TE-TDPEO), the key precursor for a direct, nucleophilic radiofluorination to yield [18F]FE-PEO. The developed radiosynthesis provides the target compound in relevantly high yield and purity, and is adaptable to routine production.

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“…Analogously, the formed 20-methylthevinone (194, Figure 52) was converted to 20,20-dimethyl-thevinone (195, 76%) and the latter to 20,20,20-trimethylthevinone (196, 59%). The latter compound was identical to the tert-butyl vinyl ketone adduct (196) of thebaine [160]. N 17 -Cycopropylmethyl-northevinone (310) was also converted in the same manner to its 20-methyl-(194, R = CPM, 98%), 20,20-dimethyl-(195, R = CPM, 91%), and 20,20,20-trimethyl-analogues (196, R = CPM, 42%), and the method was also successfully extended to numerous 7,8-constrained-and 7,7-spiro-thevinone derivatives.…”

Section: Synthesis Of Thevinone Analogues By Methylation Of Its Enolatementioning

confidence: 91%

Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations

et al. 2022

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6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged structural motif originates from a [4 + 2] cycloaddition of morphinan-6,8-dienes with dienophiles. Certain 6,14-ethenomorphinans having extremely high affinity for opioid receptors are often non-selective for opioid receptor subtypes, but this view is now undergoing some revision. The agonist 20R-etorphine and 20R-dihydroetorphine are several thousand times more potent analgesics than morphine, whereas diprenorphine is a high-affinity non-selective antagonist. The partial agonist buprenorphine is used as an analgesic in the management of post-operative pain or in substitution therapy for opiate addiction, sometimes in combination with the non-selective antagonist naloxone. In the context of the current opioid crisis, we communicated a summary of several decades of work toward generating opioid analgesics with lesser side effects or abuse potential. Our summary placed a focus on Diels–Alder reactions of morphinan-6,8-dienes and subsequent transformations of the cycloadducts. We also summarized the pharmacological aspects of radiolabeled 6,14-ethenomorphinans used in molecular imaging of opioid receptors.

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NMR Spectra and Stereochemistry of some 7‐Substituted 6,14‐Bridged Thebaine Derivatives

Cited by 24 publications

References 15 publications

NMR Analysis of a Series of 6,14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances**

NMR Analysis of a Series of 6,14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances**

Design and Synthesis of an 18F-Labeled Version of Phenylethyl Orvinol ([18F]FE-PEO) for PET-Imaging of Opioid Receptors

Diels–Alder Adducts of Morphinan-6,8-Dienes and Their Transformations

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