title: Total synthesis of a depsidomycin analogue by convergent solid-phase peptide synthesis and macrolactonization strategy for antitubercular activity.
abstract: Depsidomycin is a cyclic heptadepsi-peptide isolated from the cultured broth of Streptomyces lavendofoliae MI951-62F2. It exhibits significant antimicrobial and immunosuppressive activity. The total synthesis of a depsidomycin analogue in which 1,2-piperazine-3-carboxylic acid was substituted with proline is described. After several trials using different strategies, the desired depsidomycin analogue was obtained via stepwise synthesis starting by the amino acid 'head' and macrolactonization under Yamaguchi conditions. The cyclic depsipeptide was evaluated to have an minimum inhibitory concentration (MIC) of 4 µg/ml against H37RV and 16 µg/ml against MDR clinical strains of MTB (MDR-MTB), while the linear precursor 8 also had MICs of 4 and 16 µg/ml for the susceptible and resistant strains, respectively.
authors.affiliation: School of Chemistry, University of KwaZulu-Natal, Durban 4041, South Africa.
authors.forename: Venugopala K
authors.initials: VK
authors.lastname: Narayanaswamy
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Yacoob Mohamed
authors.initials: YM
authors.lastname: Coovadia
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
authors.forename: Glenn E M
authors.initials: GE
authors.lastname: Maguire
authors.forename: Melendhran
authors.initials: M
authors.lastname: Pillay
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000138:chemical synthesis; D007783:Lactones; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis*; D060327:Solid-Phase Synthesis Techniques; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D002264:Carboxylic Acids; D007166:Immunosuppressive Agents; D007783:Lactones; D009842:Oligopeptides; C066137:depsidomycin