Quisqualic acid

Aziridine 269 (Scheme 3.98), on treatment with pyrazole (270) and subsequent TFA deprotection, gave P-pyrazolylalanine 271, first isolated from Citrullus vulgaris (a water melon) and isosteric with histidine [148]. Treatment of 269 with 1,2,4-ox-adiazolidine-3,5-dione 272 gave (S)-quisqualic acid (273), an active ingredient of the ancient Chinese drug Shihchuntze, an anthelmintic made from the seeds of Quisqualis indica [148]. 

Quisqualic acid - has neuroexcitatory activity (stimulant of glutamic acid receptor)... 

The 1,2,4-oxadiazolidinedione ring is part of the natural amino acid L-quisqualic acid. The ring can be constructed by cyclization of ethyl 4-hydroxyallophanate (Scheme 100) <84CC1156,85CC256, 93TA2041). 

X = O, R, R = H) with tetra-(9-acetyl-)S-D-ribofuranose affords 2-(2,3,5-tri-0-acetyl-j6-D-ribofuranosyl)-l,2,4-oxadiazolidine-3,5-dione <81JMC1172). Quisqualic acid is biomimetically synthesized (8-10%) by alkylation of (226) (X = O, R , R = H) with 0-acetylserine in the presence of pyridoxal-5 -phosphate and metal ions <74CPB473,86CPB1473). A synthesis of the neurodepressant quisqualamine has been described (Scheme 102) <828781). 

A number of glutamate agonists including NMDA, kainate acid, quisqualic acid, and ibotenic acid, when applied locally, are able to destroy the cholinergic system. 

Quisqualis grandiflora Miq. Q. indica L. Q. longifolia Presl. Q. loureiri G. Don. Q. pubescens Bunn. Q. sinensis Lindl. Shi Jiun Zi (Rangoon creeper) (fruit) Quisqualic acid, trigonelline 33,235 Treat internal parasites. 

Quinene Quinic acid Quinochalone Quinonic substance Quinonoid Quinoric acid Quinquenosides Quisqualic acid r-cadinene... 

Quisqualic acid glutamate receptor agonist acting at AM PA receptors and group I mGluRs... 

Sun, X.F. and Larson, A.A. Behavioral sensitization to kainic acid and quisqualic acid in mice comparison to NMDA and substance P responses, J. Neurosci. 1991, 11, 3111-3123. 

Quisqualic acid (= (S)-ol-Amino-3,5-dioxo-l, 2,4-oxadiazolidine-2-propionic acid) (oxadiazolidine amino acid)... 

Non-NMDA-Glu-R agonist (cf. Kainic Quisqualic acids) (NMDA-Glu-R) [excitatory, excitotoxin, causal agent of human neurolathyrism]... 

Quisqualic acid (= Spa.- Quisqualis chinensis, (X indica iGlu-R agonist (pulmonate... 

Quisqualic acid (= (S)-a- Quisqualis chinensis, (A indica mClu-R (Class 1) agonist - Class... 

Biscoe, T.J., Evans, R.H., Headley, P.M., Martin, M., and Watkins, J.C. 1975. Domoic and quisqualic acids as potent amino acid excitants of frog and rat spinal neurones. Nature 255, 166-167. 

AMPA receptors bind glutamate, /VMPA, and quisqualic acid. 

Dioxo-1,2,4-Oxadiazolidines have been found as a moiety of the natural excitatory amino acid Quisqualic acid and their synthesis by numerous methods has been extensively studied by Zinner and co-workers (Ref. 256). Reaction of methyl-N-chlorocarbonyl-N-methyl carbamate, (VIII), (preparation given in section 3-3-4, this volume) with hydroxylamine affords 3,5-dioxo-4-methyl-1,2,4-oxadia-zolidine (Acronym MODD) in good yield as shown in scheme 204 (Ref. 257). 

The procedure given here describes the preparation and use of N-(benzyloxycarbonyl)-L-serine p-lactone for the synthesis of a protected -substituted alanine, N - benzyloxycarbonyl)-P—(pyrazol-l-yl)-L-alanine. This compound occurs in watermelon seeds,9 and has been used as a histidine analog.Its synthesis illustrates how serine p-lactones can provide convenient access to other p-substituted alanines such as mimosine, willardiine, quisqualic acid, and stizolobic add which occur in higher plants.5a,io Many previous chemical syntheses of racemic pyrazolylalanine have been published the best of these routes appear to be from acetamidoacryiic acid (94-96% yield) and from 0-acetylserine (40-45%).The... 

---