2026-02-19 カリフォルニア大学サンタバーバラ校(UCSB)
<関連情報>
- https://news.ucsb.edu/2026/022393/scientists-unlock-massive-new-color-palette-biomedical-research-synthesizing-non
- https://pubs.acs.org/doi/10.1021/jacs.5c20374
- https://medibio.tiisys.com/162071/
直接ペプチド合成のためのN保護/ C活性化非天然アミノ酸の簡便合成 Expedient Synthesis of N-Protected/C-Activated Unnatural Amino Acids for Direct Peptide Synthesis
Philip Kohnke,and Liming Zhang
Journal of the American Chemical Society Published: January 30, 2026
DOI:https://doi.org/10.1021/jacs.5c20374
Abstract
Unnatural amino acids play a pivotal role in protein engineering and drug discovery. However, their efficient and enantioselective synthesis remains a central challenge in organic chemistry. Here, we describe a concise and practical two-step approach for the synthesis of diverse unnatural amino acid building blocks from readily available terminal alkynes. This method utilizes mild gold(I) catalysis in combination with inexpensive chiral tert-butylsulfinamide to deliver these valuable structures with excellent enantiomeric excesses─often upgraded to enantiopurity by simple recrystallization─and broad substrate scope. These unnatural amino acid derivatives are bench-stable and preequipped with a novel t-butylsulfenyl as the N-protecting group and a mildly activated carboxylic acid, making them immediately applicable to peptide synthesis under both solution- and solid-phase conditions. Furthermore, we demonstrate their successful incorporation into multiple peptide sequences using a coupling protocol that proceeds with negligible to no epimerization, even in challenging cases.
