Halogenation of phenols and phenyl ethers with potassium halides in the presence of 18-crown-6 on oxidation with m-chloroperbenzoic acid

Srebnik, M.; Mechoulam, Raphael; Yona, Irene

doi:10.1039/p19870001423

Cited by 40 publications

(19 citation statements)

References 3 publications

(7 reference statements)

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“…48 Dimethoxy resorcinol 28 was mono-brominated to provide 2-bromo-5-(1-adamantyl)-1,3-dimethoxybenzene 29 in quantitative yields using bromine and 18-crown-6. 49 Biphenyl 31 was prepared by coupling 2-diisopropyl carbamoyl-5-methoxyphenyl boronic acid 30 with 29 under our microwave accelerated Suzuki reaction conditions. 48 Selective demethylation of biphenyl 31 with 9-I-9-BBN, followed by acetic acid catalyzed intramolecular cyclization gave cannabilactone 32 in a combined 69% isolated yield.…”

Section: Chemistrymentioning

confidence: 99%

Novel Adamantyl Cannabinoids as CB1 Receptor Probes

et al. 2013

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In previous studies compound 1 (AM411), a 3-(1-adamantyl) analog of the phytocannabinoid (−)-Δ8-tetrahydrocannabinol (Δ8-THC) was shown to have improved affinity and selectivity for the CB1 receptor. In this work, we further explored the role of the 1-adamantyl group at the C-3 position in a series of tricyclic cannabinoid analogs modified at the 9-northern aliphatic hydroxyl (NAH) position. Of these, 9-hydroxymethyl hexahydrocannabinol 11 (AM4054) exhibited high CB1 affinity and full agonist profile. In the cAMP assay, the 11-hydroxymethyl cannabinol analog 24 (AM4089) had a partial agonist profile, with high affinity and moderate selectivity for rCB1 over hCB2. In vivo results in rat models of hypothermia and analgesia were congruent with in vitro data. Our in vivo data indicates that 3-(1-adamantyl) substitution, within NAH cannabinergics, imparts improved pharmacological profiles when compared to the corresponding, traditionally used, 3-dimethylheptyl analogs and identifies 11 and 24 as a potential useful in vivo CB1 cannabinergic probes.

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Section: Chemistrymentioning

confidence: 99%

Novel Adamantyl Cannabinoids as CB1 Receptor Probes

et al. 2013

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“…[8] The fact that this reaction requires a comparatively low pH in order to proceed with a satisfactory rate has precluded its application in the synthesis of acid-labile fine chemicals for a long time. [9] This situation changed considerably in the last decades because vanadium()-dependent haloperoxidases have been isolated from various algae [10] and fungi. [11] These enzymes are able to catalyze the oxidation of, for example, Br Ϫ with H 2 O 2 under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide − A New Method for the in situ Generation of Bromine and Its Application in the Synthesis of Functionalized Cyclic Ethers

et al. 2004

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(Schiff base)vanadium(V) complexes 5 with tridentate imine auxiliaries served as catalysts for the oxidation of Br − with tert-butyl hydroperoxide (TBHP) in nonaqueous solvents. This reaction has been applied for the conversion of substituted 4-penten-1-ols into 5-exo-bromo-cyclized products, including a diastereomerically pure heterocyclic precursor used in a synthesis of the all-trans-configured 2,3,4,5-substituted tetrahydrofuran 2-epi-magnosalicin. Treatment of ω-substituted bis(homoallylic) alcohols with the reagent combination of pyHBr, TBHP, and a vanadium(V) catalyst 5 afforded 6-endo-cyclized products, i.e. brominated tetrahydropyrans, as major compounds. The results from 51 V NMR, ESI-MS, and supporting reactivity-selectivity studies indic-

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“…A method previously described 25 for obtaining halogenated resorcinols was followed for the synthesis of (-)-2-iodo-∆ 8 -tetrahydrocannabinol 34. This method involves treatment of (-)-∆ 8 -tetrahydrocannabinol 33 with sodium iodide and mchloroperbenzoic acid in the presence of 18-crown-6 at room temperature for 30 minutes (Scheme 6).…”

Section: Synthesismentioning

confidence: 99%

The role of halogen substitution in classical cannabinoids: A CB1 pharmacophore model

Nikas

Grzybowska

Papahatjis

et al. 2004

AAPS J

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The presence of halogens within the classical cannabinoid structure leads to large variations in the compounds' potencies and affinities for the CB1 receptors. To explore the structure activity relationships within this class of analogs we have used a series of halogen-substituted (-)-∆ 8 -tetrahydrocannabinol analogs and compared their affinities for the CB1 cannabinoid receptor. Our results indicate that halogen substitution at the end-carbon of the side chain leads to an enhancement in affinity with the bulkier halogens (Br, I) producing the largest effects. Conversely, 2-iodo substitution on the phenolic ring leads to a 2-fold reduction in affinity while iodo-substitution in the C1'-position of the side chain lowers the compound's affinity for CB1 by more than 8-fold. The pharmacophoric requirements resulting from halogen-substitution are explored using computer modeling methods.

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Halogenation of phenols and phenyl ethers with potassium halides in the presence of 18-crown-6 on oxidation with m-chloroperbenzoic acid

Cited by 40 publications

References 3 publications

Novel Adamantyl Cannabinoids as CB1 Receptor Probes

Novel Adamantyl Cannabinoids as CB1 Receptor Probes

The (Schiff base)vanadium(V) Complex Catalyzed Oxidation of Bromide − A New Method for the in situ Generation of Bromine and Its Application in the Synthesis of Functionalized Cyclic Ethers

The role of halogen substitution in classical cannabinoids: A CB1 pharmacophore model

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