9-Fluorenylmethoxycarbonyl-Based Solid-Phase Synthesis of Peptide α-Thioesters

Peptide thioesters play a key role in convergent protein synthesis strategies such as native chemical ligation, traceless Staudinger ligation, and Ag+-mediated thioester ligation. The Boc-based solid-phase synthesis provides a very reliable access to peptide thioesters. However, the acid lability of many peptide modifications and the requirements of most parallel peptide synthesizers call for the milder Fmoc-based solid-phase synthesis. The Fmoc-based synthesis of peptide thioesters is more cumbersome and typically proceeds with lower yields than the synthesis of peptide acids and peptide amides. The success of native chemical ligation and related technologies has sparked intensive research effort devoted to the development of new methods. The recent progress in this rapidly expanding field is reviewed. Fast ways to Rome: Peptide thioesters are key intermediates in convergent protein synthesis. Fmoc-based solid-phase synthesis usually provides rapid and reliable access to peptide derivatives; however, the base-lability of the thioester bond presents a formidable challenge. Intensive research efforts have led to the development of new methods which overcome limitations in yield and practicability. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.