title: Synthesis and cytostatic activities of didemnin derivatives.
abstract: The highly cytostatic didemnins contain a 23-membered cyclopeptolide with a side chain attached to the backbone through the amine group of threonine. Thirty-six derivatives varying the side chain were prepared, but only compounds with D-MeLeu attached to threonine show remarkable biological activities. To protect the macrocycle from degradation by lipases the two ester bonds were replaced successively by amide bonds. Although these variations have a major effect on the conformation and rigidity of the ring, the compound which contains exclusively amide bonds is highly active, equivalent to acetyl-didemnin A.
authors.affiliation: Institute of Organic Chemistry, University of Stuttgart, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schmidt
authors.forename: H
authors.initials: H
authors.lastname: Griesser
authors.forename: G
authors.initials: G
authors.lastname: Haas
authors.forename: M
authors.initials: M
authors.lastname: Kroner
authors.forename: B
authors.initials: B
authors.lastname: Riedl
authors.forename: A
authors.initials: A
authors.lastname: Schumacher
authors.forename: F
authors.initials: F
authors.lastname: Sutoris
authors.forename: A
authors.initials: A
authors.lastname: Haupt
authors.forename: F
authors.initials: F
authors.lastname: Emling
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins