title: Solid-phase total synthesis of daptomycin and analogs.
abstract: An entirely solid-phase synthesis of daptomycin, a cyclic lipodepsipeptide antibiotic currently in clinical use, was achieved using a combination of α-azido and Fmoc amino acids. This methodology was applied to the synthesis of several daptomycin analogs, one of which did not contain kynurenine or the synthetically challenging amino acid (2S,3R)-methylglutamate yet exhibited an MIC approaching that of daptomycin.
authors: Department of Chemistry, University of Waterloo , 200 University Avenue West, Waterloo, Ontario, Canada , N2L 3G1.
authors: Chuda Raj
authors: CR
authors: Lohani
authors: Robert
authors: R
authors: Taylor
authors: Michael
authors: M
authors: Palmer
authors: Scott D
authors: SD
authors: Taylor
mesh_terms: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D017576:Daptomycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005449:Fluorenes; D005971:Glutamates / Q000737:chemistry; D007737:Kynurenine / Q000737:chemistry; D015394:Molecular Structure; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D005449:Fluorenes; D005971:Glutamates; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; C046105:4-methylglutamic acid; D007737:Kynurenine; D017576:Daptomycin