A Modular and Scalable Route to Protected Cyclopropane Amino Acid Building Blocks

Swan, Charlie T.; Edmonds, Alex G.; Argent, Stephen P.; Mitchell, Nicholas J.

Abstract

An improved method for the synthesis of noncanonical cyclopropane amino acids from common laboratory reagents is described, avoiding the use of neurotoxic oxidants or precious metal catalysts. Intramolecular isocyanate trapping via a Hofmann rearrangement permits the synthesis of bicyclic carbamates in an enantioenriched and diastereopure manner. Subsequent ring-opening of these species allows access to cyclopropane amino acids which can be further functionalized via oxidation and SN2 pathways and incorporated into peptides via solid-phase peptide synthesis.

Citation

Swan, C. T., Edmonds, A. G., Argent, S. P., & Mitchell, N. J. (2025). A Modular and Scalable Route to Protected Cyclopropane Amino Acid Building Blocks. Organic Letters, 27(18), 4800-4805. https://doi.org/10.1021/acs.orglett.5c01341

• Journal Article Type: Article
• Acceptance Date: Apr 16, 2025
• Online Publication Date: Apr 24, 2025
• Publication Date: May 9, 2025
• Deposit Date: Apr 27, 2025
• Publicly Available Date: Apr 29, 2025
• Journal: Organic Letters
• Print ISSN: 1523-7060
• Electronic ISSN: 1523-7052
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 18
• Pages: 4800-4805
• DOI: https://doi.org/10.1021/acs.orglett.5c01341
• Public URL: https://nottingham-repository.worktribe.com/output/48209153
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.orglett.5c01341