Preservation of the protective group under alkaline conditions by using CaCl2. Applications in peptide synthesis

CaCl2 is shown to dramatically increase the lifetime of the Fmoc protective group in alkaline iPrOH-H2O but has little effect on hydrolytic processes. This enables efficient preparation of Fmoc-protected peptide segments by saponification of the corresponding C-terminal methyl or benzyl esters. Similarly, protected peptide segments prepared by Fmoc/tBu solid-phase synthesis can be selectively released from the support by CaCl2-catalyzed alkaline hydrolysis of an N-acylurea-based linker.