title: Solid phase synthesis of globomycin and SF-1902 A5.
abstract: The syntheses of the natural lipocyclodepsipeptide-type antibiotics globomycin and SF-1902 A(5) are reported, utilizing solid phase technology for the construction of the peptidic fragment and a new asymmetric methodology of epoxidation for the preparation of the lipidic chain. The linkage between both fragments was successfully achieved in solid phase to complete the syntheses via a macrolactonization reaction executed prior to the cleavage of the acyclic precursors from the solid support. These syntheses provide access to the rapid generation of a library of analogues via modification of the amino acid residues as well as the lipidic chain, thus facilitating the identification of new antibiotics with interesting mechanisms of action based upon the inhibition of the enzyme signal peptidase II.
authors.affiliation: Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s/n 29071, Malaga, Spain. frsarabia@uma.es
authors.forename: Francisco
authors.initials: F
authors.lastname: Sarabia
authors.forename: Samy
authors.initials: S
authors.lastname: Chammaa
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Ruiz
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; D010456:Peptides, Cyclic; C017339:globomycin; D016282:Aspartic Acid Endopeptidases; C095652:signal peptidase II