A combined solid- and solution-phase approach provides convenient access to analogues of the calcium-dependent lipopeptide antibioticsElectronic supplementary information (ESI) available: Preparation of Fmoc-(Dmb)Gly-OH and analytical RP-HPLC traces, CD spectra, and 2D-NMR spectra for peptides 2, 3, ent-2 and ent-3. See DOI: 10.1039/c3ob42238k

• Main Authors: Hart, Peter 't, Kleijn, Laurens H. J, de Bruin, Gerjan, Oppedijk, Sabine F, Kemmink, Johan, Martin, Nathaniel I
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob42238k

The calcium-dependent lipopeptide antibiotics represent a promising new class of antimicrobials for use in combating drug-resistant bacteria. At present, daptomycin is the only such lipopeptide used clinically and displays potent antimicrobial activity against a number of pathogenic Gram-positive bacteria. Given the increasing need for new antibiotics, practical synthetic access to unnatural analogues of daptomycin and related antimicrobial lipopeptides is of value. We here report an efficient synthetic route combining solid- and solution-phase techniques that allows for the rapid preparation of daptomycin analogues. Using this approach, four such analogues, including two enantiomeric variants, were synthesized and their antimicrobial activities and hydrolytic stabilities evaluated. A synthetic route combining solid- and solution-phase techniques allows for the rapid preparation of daptomycin analogues.