Synthesis and glutamate-agonistic activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-3-isoxazolyl)-propanoic acid derivatives.
(S)-2-Amino-3-(2,5-dihydro-5-oxo-3-isoxazolyl)propanoic acid, (3a) and its analogs (3b--h) were prepared and evaluated for glutamate receptor-agonistic and antifungal activities. Several (S)- and (R)-2-amino-3-isoxazolylpropanoic acid derivatives (3a--d) were synthesized starting with (S)- and (R)-N-tert-butoxycarbonyaspartic acid alpha-methyl esters (4, n = 1) by means of Masamune's chain extension reaction followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions. Furthermore, (S)- and (R)-N-tert-butoxycarbonylglutamic acid alpha-methyl esters (4, n = 2) were converted to (S)- and (R)-2-amino-4-isoxazolylbutyric acid derivatives (3e-h) via the same sequence of reactions.
Tamura
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N
Chemistry Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Iwama
T
T
Itoh
K
K
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000935:Antifungal Agents; D007555:Isoxazoles; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter