Synthesis of enantiomerically enriched β- <i>N</i> -amino ( <i>S</i> )-α-alanine analogs <i>via</i> sequential reactions on a chiral Ni( <scp>ii</scp> ) complex

A concise synthetic route to enantiomerically enriched β-<i>N</i>-substituted (<i>S</i>)-α-diaminopropanoic acids is reported. An acetylene group was introduced into the alanine side chain by nucleophilic Michael addition of substituted propargylamines to the dehydroalanine moiety in a chiral Ni(II) complex, which afforded β-<i>N</i>-propargylamino derivatives in high ee (≈90%). Subsequent Glaser, Sonogashira, and [3 + 2]-cycloaddition reactions delivered structurally diverse products with ee up to 99%. The isolated auxiliary (<i>S</i>)-BPB can be recovered and reused without any loss of enantiointegrity. Biological screening of the products identified (<i>S</i>)-3-(<i>N</i>-(1-phenylethyl)-<i>N</i>-(prop-2-ynyl)amino)-2-aminopropanoic acid as a moderate bacterial collagenase inhibitor (IC₅₀ = 0.69 mM), demonstrating the potential of this platform for enzyme inhibitor development.