کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1363152 981504 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aerobic oxidation of indolomorphinan without the 4,5-epoxy bridge and subsequent rearrangement of the oxidation product to spiroindolinonyl-C-normorphinan derivative
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Aerobic oxidation of indolomorphinan without the 4,5-epoxy bridge and subsequent rearrangement of the oxidation product to spiroindolinonyl-C-normorphinan derivative
چکیده انگلیسی

Aerobic oxidation of indolomorphinan 1 without a 4,5-epoxy bridge proceeded in the presence of platinum catalyst to give indoleninomorphinan 2 or quinolono-C-normorphinan 5. The 4-hydroxy group would play an important role in deciding the course of the reaction. Treatment of 2a with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave spiroindolinonyl-C-normorphinan 3a whose structure resembles that of δ opioid receptor agonist spiroindanyloxymorphone (SIOM). Boron trichloride was effective for the reverse reaction from 3a to 2a without side reaction. This practical interconversion method between hydroxyindolenine and spiroindolinone would be useful for the design and construction of drug-like compound libraries. Although the compound 3b was expected to show the selectivity for δ opioid receptor because of the structural resemblance to SIOM, it was rather selective for μ opioid receptor (μ: Ki = 0.75 nM; δ: Ki = 2.90 nM; κ: Ki = 13.4 nM). The result suggests that the slight difference of the spatial location of the benzene rings in these compounds may definitively affect the binding affinity for δ opioid receptor.

Indolomorphinan without 4,5-epoxy bridge 1a was easily oxidized to give indoleninomorphinan 2a. Practical interconversion between indoleninomorphinan 2a and spiroindolinonyl-C-normorphinan 3a became possible.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 16, 15 August 2009, Pages 5983–5988
نویسندگان
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