Synthesis and cytostatic activities of didemnin derivatives.
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.
Schmidt
U
U
Institute of Organic Chemistry, University of Stuttgart, Germany.
Griesser
H
H
Haas
G
G
Kroner
M
M
Riedl
B
B
Schumacher
A
A
Sutoris
F
F
Haupt
A
A
Emling
F
F
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
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins