Towards the use of the base-induced Staudinger Ligation in the synthesis of cyclic peptides

ORGN 938

Christian P R Hackenberger, hackenbe@chemie.fu-berlin.de, Institute of Chemistry and Biochemistry, FU Berlin, Takustr. 3, Berlin, 14059, Germany
In order to develop a general route towards head-to-tail cyclic peptides and proteins we propose the use of the Base-induced Staudinger Ligation as a chemoselective amide bond forming reaction. Our investigations reveal that the Staudinger Ligation of borane-protected phosphinothiols can be induced at mild conditions (40 °C, 24h), which can be utilized in peptide synthesis. Different synthetic strategies for peptide thioesters with protected phosphinothiols are presented and compared. Finally, the influence of different solvents on the cyclization yield is discussed. These findings are then applied towards the synthesis of small naturally occurring cyclic peptides.