 | |
| Names | |
|---|---|
| IUPAC name (2S,4R)-2-Amino-4-methylpentanedioic acid | |
| Other names (2S,4R)-4-Methylglutamic acid | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
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| Properties | |
| C6H11NO4 | |
| Molar mass | 161.157 g·mol−1 |
| Appearance | White solid |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
SYM-2081 is a highly selectiveagonist for thekainate receptor. This potent agonist has nearly 3,000 fold- and 200-fold selectivity forkainate receptors overAMPA andNMDA receptors, respectively.[1] Given its potency and selectivity, it is a useful ligand for studying the role ofkainate receptors in thecentral nervous system.[2]
SYM-2081 can be prepared through diastereomeric mixture via enzymatic synthesis, but the yield of this reaction is small.[3] SYM-2081 can be produced at a multi-gram scale by starting with (S)-1-t-butoxycarbonyl-5-t-butyldiphenylsilyoxymethylpyrrolidine-2-one and treating it with one equivalent oflithium bis(trimethylsilyl)amide intetrahydrofuran (THF) at -78 °C.[3] The resulting product was mixed with excessiodomethane which yielded 4-methylated products and some unreacted starting material.[3] The trans product was purified throughcolumn chromatography.[3] Next, the product was crystallized by hexanes.[3]Tetrabutylammonium fluoride was used for its primary alcohol to selectively remove thetert-butyldiphenylsilyl (TBDPS) protecting group.[3] The Sharpless procedure was used tooxidize the alcohol.[3] This intermediate was hydrolyzed withlithium hydroxide inaqueous THF.[3] Finally, the compound was treated withtrifluoroacetic acid (TFA) indichloromethane to produce (2S,4R)-4-methylglutamic acid.[3]
Some research has indicated that having the methyl group in SYM-2081 is essential for its potency.[2] SYM-2081 was 20 times more potent than its (2R,4R) isomer and 1000 times more potent than its (2S,4S) isomer.[2]
