ISSN:
1434-193X
Keywords:
3-Hydroxyisoxazoles
;
Alkylation
;
Protecting groups
;
Muscimol
;
GABA analogues
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
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