HF-Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization

What is it about?

Want to use Boc chemistry to make peptides but afraid of HF? This is an easy, cheap alternative. Boc SPPS can make some very high quality peptides because of the purity of the starting materials and the efficiency of acid deprotection cycles. By reverting to the original resin developed by Merrifield you can cleave the peptide under much milder conditions that are compatible with a wider range of PTMs than the use of anyhydrous HF. Its also a direct method for making peptide thioesters which can be directly used to make cyclic peptides.

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Why is it important?

Boc SPPS is a great way to make pure peptides but it has one major drawback in comparison to Fmoc SPPS; the use of anhydrous HF, an extremely hazardous reagent. The use of HF is also time consuming, requires dedicated fume hood, equipment and good training. HF is also increasingly difficult to source. This alternative can be carried out by the same practical procedure as used for Fmoc and lends itself to small scale and parrallel synthesis.