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PreprintCC BYChemRxiv

Aminomutase-Inspired Methylene Insertion for α-to-β Homologative Transposition of Amino Acids

  • Ayah W. Fidama1,2
  • Vincent Huang1,2
  • Yetong Lin1,2
  • Jaclyn N. Mauro1,2
  • Ethan T. A. Raffman1,2
  • Jialin Li1,2
  • Jeffrey M. Lipshultz1,2,3
  1. 1Department of Chemistry
  2. 2Stony Brook University
  3. 3Institute of Chemical Biology and Drug Discovery
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Abstract

A versatile method for the preparation of synthetically valuable β2-homologated amino acid esters from simple α-amino acid esters is described. Inspired by pyridoxal 5′-phosphate-dependent aminomutase enzymes, the described strategy exploits a straightforward protocol for substrate activation, alkylation, and migration leveraging a bio-inspired 3-exo-trig radical cascade. This approach enables a novel homologative strategy towards β-amino acids via methylene insertion into the Cα–N bond of α-amino acids. A broad substrate scope is demonstrated, and key activator electronic factors are elucidated through experimental and computational mechanistic studies. By engaging α-amino acids directly, the method provides unique access to β2-homologated amino acids.

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Cite

BibTeXRIS
BibTeX
@misc{fidama2026aminomutaseinspired,
  title = {{Aminomutase-Inspired Methylene Insertion for α-to-β Homologative Transposition of Amino Acids}},
  author = {Ayah W. Fidama and Vincent Huang and Yetong Lin and Jaclyn N. Mauro and Ethan T. A. Raffman and Jialin Li and Jeffrey M. Lipshultz},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15009423/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009423/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Aminomutase-Inspired Methylene Insertion for α-to-β Homologative Transposition of Amino Acids
AU  - Ayah W. Fidama
AU  - Vincent Huang
AU  - Yetong Lin
AU  - Jaclyn N. Mauro
AU  - Ethan T. A. Raffman
AU  - Jialin Li
AU  - Jeffrey M. Lipshultz
PY  - 2026
DA  - 2026/09/24
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15009423/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009423/v1
AB  - A versatile method for the preparation of synthetically valuable β2-homologated amino acid esters from simple α-amino acid esters is described. Inspired by pyridoxal 5′-phosphate-dependent aminomutase enzymes, the described strategy exploits a straightforward protocol for substrate activation, alkylation, and migration leveraging a bio-inspired 3-exo-trig radical cascade. This approach enables a novel homologative strategy towards β-amino acids via methylene insertion into the Cα–N bond of α-amino acids. A broad substrate scope is demonstrated, and key activator electronic factors are elucidated through experimental and computational mechanistic studies. By engaging α-amino acids directly, the method provides unique access to β2-homologated amino acids.
ER  -