Solid-phase synthesis of a cyclodepsipeptide: cotransin.
The first solid-phase synthesis of cotransin--a 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.
Coin
Irene
I
Leibniz-Institute of Molecular Pharmacology (FMP), Robert-Rössle-Str.10, D-12135 Berlin, Germany. coin@fmp-berlin.de
Beerbaum
Monika
M
Schmieder
Peter
P
Bienert
Michael
M
Beyermann
Michael
M
D000596:Amino Acids / Q000737:chemistry; D003500:Cyclization; D005449:Fluorenes / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011137:Polystyrenes / Q000737:chemistry
D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010456:Peptides, Cyclic; D011137:Polystyrenes; C502316:cotransin; D019344:Lactic Acid