Synthesis of the very acid‐sensitive Fmoc‐Cys(Mmt)‐OH and its application in solid‐phase peptide synthesis

Abstract

S‐4‐methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc‐Cys(Mmt)‐OH by its reaction with Fmoc‐OSu. As compared to the corresponding Fmoc‐Cys(Trt)‐OH, the S‐Mmt‐function was found to be considerably more acid labile. Quantitative S‐Mmt‐removal occurs selectively in the presence of groups of the tert butyl type and S‐Trt by treatment with 0.5–1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr¹‐somatostatin on 2‐chlorotrityl resin. In this synthesis groups of the Trt‐type were exclusively used for amino acid side‐chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM–TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions. © Munksgaard 1996.