Application of Fmoc-His(Boc)-OH in Fmoc-based SPPS

Summary

This application note demonstrates that His(Boc) is a powerful His derivative that can be effectively coupled at 90 °C, providing favorable crude purity while both decreasing coupling time and dramatically reducing epimerization. Fmoc-His(Boc)-OH is widely available as compared to other epimerization suppressing Nπ protected derivatives while maintaining comparable synthetic performance. In summary, the key benefits of Fmoc-His(Boc)-OH are:

• Commercial bulk availability and competitive price relative to Fmoc-His(Trt)-OH.
• Low epimerization levels at elevated temperatures; coupling temperatures of 50 °C and below make Fmoc-His(Boc)-OH applicable for use in the synthesis of active pharmaceutical ingredients and avoiding complex coupling reagents and conditions.
• Excellent solution stability; comparable to Fmoc-His(π-Mbom)-OH and greater than Fmoc-His(Trt)-OH.