Evaluation of Protecting Groups for 3‐Hydroxyisoxazoles − Short Access to 3‐Alkoxyisoxazole‐5‐carbaldehydes and 3‐Hydroxyisoxazole‐5‐carbaldehyde, the Putative Toxic Metabolite of Muscimol

doi:10.1002/(SICI)1099-0690(199803)1998:3<473::AID-EJOC473>3.0.CO;2-V

Paper

Evaluation of Protecting Groups for 3‐Hydroxyisoxazoles − Short Access to 3‐Alkoxyisoxazole‐5‐carbaldehydes and 3‐Hydroxyisoxazole‐5‐carbaldehyde, the Putative Toxic Metabolite of Muscimol

Published Mar 1, 1998 · R. Riess, M. Schön, S. Laschat

European Journal of Organic Chemistry

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Abstract

The regioselectivity of the 3-hydroxyisoxazole-5-ester 1 is studied with respect to O- versus N-alkylation. 3-O-Alkyl products 2 are highly favoured with benzyl, benzhydryl, and allyl bromide (≥ 91:9), in contrast to known uses of 5-alkyl-3-hydroxyisoxazoles or when methylation with diazomethane (or methyl iodide) is effected. Methoxymethylation leads to the N-substituted isoxazolinone 3e only. On reduction with DIBAH, the esters 2 afford 3-O-protected 3-hydroxyisoxazole-5-carbaldehydes 4 (75−98%). For removal of the benzyl protecting groups, three variations (HBr/HOAc, H2-Pd/BaSO4, NBS/AIBN) were found useful with 5-ester, 5-formyl, and 5-hydroxymethyl derivatives. The free 3-hydroxy-5-carbaldehyde 9, the putative toxic metabolite of the GABA agonist muscimol, is prepared accordingly. The O-protected 3-hydroxyisoxazole-5-carbaldehydes 4 constitute versatile intermediates in various routes to analogues of CNS-active amino acids and can now be obtained in a highly efficient manner.

Study Snapshot

This study demonstrates a highly efficient method for preparing 3-O-protected 3-hydroxyisoxazole-5-carbaldehydes, which can be used as versatile intermediates in various CNS-active amino acid pathways.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Evaluation of Protecting Groups for 3‐Hydroxyisoxazoles − Short Access to 3‐Alkoxyisoxazole‐5‐carbaldehydes and 3‐Hydroxyisoxazole‐5‐carbaldehyde, the Putative Toxic Metabolite of Muscimol

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Citations

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4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel.

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