Open-Flask Protocol for the Removal of Alloc Carbamate and Allyl Ester Protecting Groups. Application to In-solution and On-resin Peptide Synthesis

J Org Chem. 2024 Dec 13. doi: 10.1021/acs.joc.4c02115. Online ahead of print.

Abstract

The standard protocol for Alloc group removal during peptide synthesis still presents limitations, including low reaction yields, N-allylated byproducts, and the use of air-sensitive Pd(PPh3)4. We addressed these challenges by developing a novel protocol using the air-stable Pd(PPh3)2Cl2 catalyst, Meldrum's acid (MA), and triethylsilane (TES-H). This combination ensured high yields, eliminated N-allylated byproducts, and is compatible with automated synthesis. This cost-effective and efficient method shows promise for widespread use in peptide chemistry applications and beyond.