- The Synthesis and Evaluation of Fluoro-, Trifluoromethyl-, and Iodomuscimols as GABA Agonists
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Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C-4 fluorine-containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor.
- Abdul Manan, Mohd Abdul Fatah,Cordes, David B.,Slawin, Alexandra M. Z.,Bühl, Michael,Liao, Vivian W. Y.,Chua, Han. C.,Chebib, Mary,O'Hagan, David
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- A CONVENIENT SYNTHESIS OF MUSCIMOL BY A 1,3-DIPOLAR CYCLOADDITION REACTION
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A simple and large scale approach to the synthesis of muscimol 7 has been developed starting from the easily available dibromoformaldoxime 1.
- Chiarino, D.,Napoletano, M.,Sala, A.
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- An improved synthesis of muscimol
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A regiospecific 1,3-dipolar cycloaddition/elimination is the key-step of a convenient, gram-scale synthesis of the GABA-agonist muscimol (1).
- Pevarello,Varasi
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p. 1939 - 1948
(2007/10/02)
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- Structure elucidation of pantherine, a flycidal alkaloid from Amanita pantherina (DC.) FR.
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Pantherine is identified as 5-aminomethyl-3-hydroxyisoxazole by means of spectroscopic experiments and chemical correlation with synthetic compounds.
- Konda,Takahashi,Onda
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p. 1083 - 1087
(2007/10/02)
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- Generation and Reactions of the Dianion of 3-Hydroxy-5-methylisoxazole, a Covenient β-Keto Amide Sython. Total Synthesis of Muscimol
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The title compound (4) has been prepared by treatment of diketene with N,O-bis(trimethylsilyl)hydroxylamine (2) to give N-(trimethylsilyloxy)-N-(trimethylsilyl)acetoacetamide (3) as a stable liquid.Treatment of 3 with methanolic HCl removed the Me3Si protective groups and cyclized the resulting hydroxamic acid to isoxazole 4 in good yield.The dianion of 4 was generated with lithium diisopropylamide and was found to react exclusively at the 5-methyl group when treated with electrophiles.The reactions of the dianion which were accomplished included carboxylation with CO2, alkylation with benzyl chloride, condensation with benzophenone, and acylations with dimethyl carbonate, methyl acetate, N,N-dimethylacetamide, N-methoxy-N-methylacetamide, ethyl benzoate, and ethyl benzoylacetate.Hydrogenation of condensation products (10, 11, 13, 14, and 15) using optimum conditions of the catalyst and solvent gave the corresponding β-keto amides (16, 17, 18, 19, and 20, respectively) in excellent yields.Treatment of the dianion with isoamyl nitrite gave 3-hydroxy-5-isoxazolecarboxaldehyde oxime (21) in good yield.Acetylation of 21 to the diacetate 22 followed by reduction with BH3-THF gave muscimol (1), a constituent of the mushroom Amanita muscaria.
- Oster, Timothy A.,Harris, Thomas M.
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p. 4307 - 4311
(2007/10/02)
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- DIRECT PHENYLATION OF ISOXAZOLES USING PALLADIUM CATALYSTS. SYNTHESIS OF 4-PHENYLMUSCIMOL
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Several 4-phenylisoxazoles were synthesized by the palladium-catalyzed coupling of the isoxazole ring with benzene or iodobenzene.Compound 4, thus obtained, was converted to 4-phenylmuscimol (2), according to the newly developed route to muscimol (1) from 3.
- Nakamura, Norio,Tajima, Yawara,Sakai, Kiyoshi
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p. 235 - 245
(2007/10/02)
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