title: Total synthesis of daptomycin by cyclization via a chemoselective serine ligation.
abstract: A total synthesis of daptomycin, the first natural product antibiotic launched in a generation, was achieved. This convergent synthesis relies on an efficient macrocyclization via a serine ligation to assemble the 31-membered cyclic depsipeptide. The difficult esterification by the nonproteinogenic amino acid kynurenine was accomplished via the esterification of a threonine residue by a suitably protected Trp ester, followed by ozonolysis. This synthesis provides a foundation and framework to prepare varied analogues of daptomycin to establish its structure-activity profile.
authors.affiliation: Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, People's Republic of China.
authors.forename: Hiu Yung
authors.initials: HY
authors.lastname: Lam
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.forename: Jianchao
authors.initials: J
authors.lastname: Xu
authors.forename: Clarence T T
authors.initials: CT
authors.lastname: Wong
authors.forename: Ci
authors.initials: C
authors.lastname: Xu
authors.forename: Xuechen
authors.initials: X
authors.lastname: Li
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D003500:Cyclization; D017576:Daptomycin / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007737:Kynurenine / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry; D008024:Ligands; D010126:Ozone / Q000737:chemistry; D012694:Serine / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D007769:Lactams; D008024:Ligands; D013912:Threonine; D007737:Kynurenine; D012694:Serine; D010126:Ozone; D017576:Daptomycin