Expedient synthesis of a novel class of pseudoaromatic amino acids: Tetrahydroindazol-3-yl- and tetrahydrobenzisoxazol-3-ylalanine derivatives

Middleton, Richard J.; Mellor, Sarah L.; Chhabra, Siri Ram; Bycroft, Barrie W.; Chan, Weng C.

Abstract

A concise synthesis of novel homochiral aromatic amino acid surrogates comprising a tetrahydroindazole or a benzisoxazole system was developed via the acylation of a cyclic 1,3-diketone by the side-chain carboxyl functionality of either Boc-Asp-OtBu or Boc-Glu-OtBu followed by regioselective condensation with hydrazine, N-benzylhydrazine and hydroxylamine. The tetrahydroindazole nucleus was also constructed by the condensation of Boc-Asp-OtBu with the enamine, 1-pyrrolidino-1-cyclohexene followed by acid-hydrolytic treatment and reaction with hydrazines. Further functional group transformations gave N α-Fmoc-protected derivatives as useful building blocks for solid-phase peptide assembly. © 2003 Elsevier Ltd. All rights reserved.

Citation

Middleton, R. J., Mellor, S. L., Chhabra, S. R., Bycroft, B. W., & Chan, W. C. (2004). Expedient synthesis of a novel class of pseudoaromatic amino acids: Tetrahydroindazol-3-yl- and tetrahydrobenzisoxazol-3-ylalanine derivatives. Tetrahedron Letters, 45(6), 1237-1242. https://doi.org/10.1016/j.tetlet.2003.11.133

• Journal Article Type: Article
• Acceptance Date: Nov 27, 2003
• Online Publication Date: Dec 13, 2003
• Publication Date: Feb 2, 2004
• Deposit Date: May 12, 2023
• Journal: Tetrahedron Letters
• Print ISSN: 0040-4039
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 45
• Issue: 6
• Pages: 1237-1242
• DOI: https://doi.org/10.1016/j.tetlet.2003.11.133
• Public URL: https://nottingham-repository.worktribe.com/output/3137764
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0040403903028983?via%3Dihub