Nitrile oxides in medicinal chemistry-2. synthesis of the two enantiomers of dihydromuscimol

✍ Scribed by Marco De Amici; Carlo De Micheli; Valeria Misani

• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 821 KB
• Volume: 46
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)89765-9

✦ Synopsis

The cycloaddition of bromonitrile oxide to monosubstituted ole,Gs has a high regioselectivity yielding 3-bromo-S-substhuted isoxazolines contaminated by minor amounts (4-9%) of the I-substituted isomer. The adducts of bromonitrile oxide to ally1 a3lcohol and N-protected allylamine were employed as hey intermediates in the preparation of race&c dihydromuscimol (DHM). The synthesis of (R)-(-)-and (S)-(+)-DHM was accomplished by using the two diastereomers obtained by the cycloaadition of bromonitrile oxide to (S)-(+)-isopropylidene-3-buten-I&diol. The enantiomeric excesses of (R)-(-)-and (S)-(+)-DHiU, determined by capillary GLC on the appropriate precursors, were 98.8 and >99.0 %. A spectroscopic survey of the tautomerism of 3-hydroxyisoxazolines indicates the predomiMnt or exclusive occurrence of the NHform.