Stable cyclopropene-containing analogs of the amino acid neurotransmitter glutamate

• Published in: Tetrahedron letters Vol. 60; no. 22; pp. 1476 - 1480
• Main Authors: Kumar, Pratik, Huang, Wei, Shukhman, David, Camarda, Frank M., Laughlin, Scott T.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 30.05.2019; Elsevier
• Subjects: Bioorthogonal chemistry; chemical reactions; chemical structure; Chemistry; Chemistry, Organic; Cyclopropene; Glutamate; glutamic acid; glutathione; Lewis bases; Neurotransmitter; neurotransmitters; organic compounds; Physical Sciences; Science & Technology; storage time; Cyclopropene; Neurotransmitter; Glutamate; Bioorthogonal chemistry; PHARMACOLOGY; EFFICIENT; TAGS
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2019.04.046

[Display omitted] •Applying bioorthogonal chemistry to neuroscience with cyclopropene bearing neurotransmitter analogs.•Shorter and half-gram scale synthesis of cyclopropene-analogs of glutamate.•Generation of novel forms of structurally constrained glutamate analogs. As a neurotransmitter, the amino acid glutamate has been the subject of efforts to generate structural analogs with unique properties. Here we report a practical, half-gram synthesis of two cyclopropene-containing glutamate analogs. These analogs are stable in solution, in the presence of the biological nucleophile glutathione, upon concentration, and during long-term storage, while maintaining their amenability to photo- or enzyme-caging and reactivity with bioorthogonal reaction partners like s-tetrazine or light-activated tetrazoles.