Solid-Phase Synthesis of a Cyclodepsipeptide: Cotransin
I. Coin; M. Beerbaum; P. Schmieder; M. Bienert; M. Beyermann
Org. Lett. Epub 2008 Jul 24
The first solid-phase synthesis of cotransina cyclic depsipeptide having high pharmacological potential was achieved, by a proper choice of coupling reagents and use of either TBAF or DBU for Fmoc removal to suppress the otherwise dominating, sequence-derived diketopiperazine formation. Starting the assembly from C-terminal lactic acid allowed fast and epimerization-free cyclization in solution. Novel conditions for orthogonal use of the Fmoc/Bsmoc-protection system were discovered, and an unexpected nucleophilic behavior of DBU was observed.