Importance of repulsion of lone electron pairs in the enhanced reactivity of 1,8-naphthyridine and the large α-effect of hydrazine in the aminolyses of <i>p</i>-toluenesulfonyl chloride

Ōae, Shigeru; Kadoma, Yoshihito

doi:10.1139/v86-196

Cited by 11 publications

(1 citation statement)

References 13 publications

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“…Molecular orbital calculations (AM1, Macspartan), comparing the electron distribution in the highest occupied molecular orbitals of the radicals from diethyl malonate and the 3-phenylisoxazolone were informative. In the former, as expected, [20] almost all the electron spin is localized on carbon, but for the isoxazolone radical more electron spin is localized on nitrogen than on carbon, in accord with our experimental observations.…”

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Some Synthetic Approaches to Glutamate AMPA Receptor Agonists Based on Isoxazolones

Cox¹,

Jahangiri²,

Perkins³

et al. 2004

Aust. J. Chem.

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Several approaches to the synthesis of derivatives of the antifungal antibiotic TAN-950A, which is also an agonist of glutamate at hippocampal neurons, are reported. Additions of isoxazolon-4-yl anions to methyleneoxazolidinones were not useful because addition occurred predominantly through N-2. Similarly addition of the isoxazolon-4-yl radicals to model Michael acceptors occurred predominantly through N-2. Racemic analogues of TAN-950A were prepared by reaction of isoxazolone Mannich bases with acetylaminomalonate or addition of β-ketoester anions to dehydroalanines. The best approach to enantiomerically pure analogues was by acylation of pyroglutamates, followed by reaction with hydroxylamine.(S)-Glutamic acid 1 (Scheme 1) is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). Excitatory amino acid receptors are believed to play a variety of physiological roles in mammals, ranging from the processing of sensory information, to coordinated movement patterns, cognitive processes, learning, and memory. [1] Changes in glutamate transmission have been associated with several neurological disorders including acute neurodegeneration, pain, epilepsy, and possibly chronic neurodegenerative diseases such as Alzeimer's, Parkinson's, and Huntington's diseases, depression, drug dependency, and schizophrenia. [1] Glutamate combines with two types of CNS receptors. These are ionotropic receptors (iGluRs), which open an associated ion channel, and metabotropic receptors (mGluRs), which have seven transmembrane spanning regions and modulate secondary messenger systems.We are interested in one of the three subtypes of ionotropic receptors of (S)-glutamic acid, the receptors activated by AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate) 2. [2] Although extensive research has been carried out on the other sub-receptor sites, [3,4] the AMPA receptor subtype has received much less attention.

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confidence: 92%