SYM-2081
Chemical compound
From Wikipedia, the free encyclopedia
SYM-2081 is a highly selective agonist for the kainate receptor. This potent agonist has nearly 3,000 fold- and 200-fold selectivity for kainate receptors over AMPA and NMDA receptors, respectively.[1] Given its potency and selectivity, it is a useful ligand for studying the role of kainate receptors in the central nervous system.[2]
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| Names | |
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| IUPAC name
(2S,4R)-2-Amino-4-methylpentanedioic acid | |
| Other names
(2S,4R)-4-Methylglutamic acid | |
| Identifiers | |
3D model (JSmol) |
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
PubChem CID |
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CompTox Dashboard (EPA) |
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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 their standard state (at 25 °C [77 °F], 100 kPa).
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Synthesis
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 of lithium bis(trimethylsilyl)amide in tetrahydrofuran (THF) at -78 °C.[3] The resulting product was mixed with excess iodomethane which yielded 4-methylated products and some unreacted starting material.[3] The trans product was purified through column chromatography.[3] Next, the product was crystallized by hexanes.[3] Tetrabutylammonium fluoride was used for its primary alcohol to selectively remove the tert-butyldiphenylsilyl (TBDPS) protecting group.[3] The Sharpless procedure was used to oxidize the alcohol.[3] This intermediate was hydrolyzed with lithium hydroxide in aqueous THF.[3] Finally, the compound was treated with trifluoroacetic acid (TFA) in dichloromethane to produce (2S,4R)-4-methylglutamic acid.[3]