Chemistry:SYM-2081
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| Names | |
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| IUPAC name
(2S,4R)-2-Amino-4-methylpentanedioic acid
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| Other names
(2S,4R)-4-Methylglutamic acid
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| Identifiers | |
3D model (JSmol)
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PubChem CID
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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). | |
| Infobox references | |
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]
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]
Research
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]
References
- ↑ "SYM 2081". https://www.rndsystems.com/products/sym-2081_0903.
- ↑ 2.0 2.1 2.2 Donevan, S. D.; Beg, A.; Gunther, J. M.; Twyman, R. E. (May 1998). "The methylglutamate, SYM 2081, is a potent and highly selective agonist at kainate receptors". The Journal of Pharmacology and Experimental Therapeutics 285 (2): 539–545. ISSN 0022-3565. PMID 9580595. https://pubmed.ncbi.nlm.nih.gov/9580595.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Zi-Qiang Gu; Xiao-Fa Lin; Hesson, David P. (1995). "Diastereoselective synthesis of (2S,4R)-4-Methylglutamic acid (sym 2081): A high affinity and selective ligand at the kainate subtype of glutamate receptors". Bioorganic & Medicinal Chemistry Letters 5 (17): 1973–1976. doi:10.1016/0960-894x(95)00335-q. https://doi.org/10.1016/0960-894X(95)00335-Q. Retrieved 2021-12-10.
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