Nickel-Catalyzed Deallylation for Sustainable Solution and Solid-Phase Peptide Synthesis

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Traditional allyl/alloc deprotection often relies on expensive palladium catalysts.
• Existing base-metal alternatives show limited compatibility with on-resin solid-phase peptide synthesis (SPPS).

Purpose of the Study:

• To develop a cost-effective, one-step nickel-catalyzed method for allyl/alloc deprotection.
• To establish a protocol compatible with solid-phase peptide synthesis (SPPS), including on-resin applications.

Main Methods:

• A two-component system utilizing an air-stable Ni(PPh₃)₂Br₂ precatalyst and NH₃BH₃ reductant was employed.
• The reaction was performed rapidly in SPPS-compatible solvents under inert conditions.

Main Results:

• The nickel-catalyzed protocol achieved efficient and chemoselective deprotection of allyl- and alloc-protected amino acids, small molecules, and peptides in solution.
• The method was successfully extended to on-resin deprotection, demonstrating its utility in SPPS.

Conclusions:

• This one-step nickel-catalyzed deprotection method provides a viable, cost-effective alternative to palladium-based systems for SPPS.
• The demonstrated on-resin compatibility offers significant promise for advancing peptide synthesis strategies.