A solid-phase synthetic route to N-acylated α-alkyl-d,l-homoserine lactones

[Display omitted] •Novel, acylated homoserine lactones with quaternized alpha position are now accessible.•Unnatural Peptide Synthesis (UPS) utilized to generate quaternary alpha carbon.•Ten quaternized derivatives are candidates for evaluation as quorum-sensing modulators. A synthetic route to N-acylated α-alkyl-d,l-homoserine lactones was established using solid-phase unnatural peptide synthesis (UPS) and combinatorial chemistry. The application of UPS methodology allowed access to racemic N-acylated homoserine lactones (d,l-AHLs) and their α-alkyl structural analogs (α-R1-d,l-AHLs). The synthesis and characterization of a library of five d,l-AHLs and ten α-R1-d,l-AHLs prepared from resin-bound amino acids is reported.