- Equilibrium control in bromomethylation: An expedient route to 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)
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The excitatory amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) has been prepared in gram quantities in 42% total yield by a three-step procedure from 3-hydroxy-5-methylisoxazole. It is shown how bromomethylation may be optimized through control of the involved equilibria and how N-protecting methoxymethyl groups can be removed.
- Begtrup,Slok
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- Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation
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We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.
- Asad, Naeem,Deodato, Davide,Dore, Timothy M.
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supporting information
p. 5589 - 5594
(2021/07/02)
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- An efficient and general enantioselective synthesis of some isoxazole- containing analogues of the neuroexcitant glutamic acid
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Isoxazole amino acids are an important class of neuroexcitant which are difficult to prepare in enantiopure form. Diastereoselective alkylation of the enantiomerically pure glycine derivative, tert-butoxycarbonyl-2-(tert- butyl)-3-methyl-4-oxo-1-imidazolidinecarboxylate (Boc-BMI) with 4- bromomethyl-2-methoxymethyl-5-methylisoxazolin-5-one 5 or 5-bromomethyl-4- bromo-3-methoxyisoxazole, gives intermediates which under mild hydrolysis conditions produce the amino acids (S)- and (R)-bromohomoibotenic acid and (S)- and (R)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid with e.e. >99%.
- Pajouhesh, Hassan,Curry, Kenneth
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p. 2757 - 2760
(2007/10/03)
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