Electrochemical Oligopeptide Synthesis Assisted By a Soluble Tag Method

Abstract

Recently, peptides have attracted much attention as the medicinal candidates with higher specificity and lower side effects than small molecular medicines. Peptides have been synthesized using stoichiometric amount of coupling reagents. While these reagents enable quantitative reaction, stoichiometric byproducts from coupling reagents cause poor atom economy. In this context, “General methods for catalytic/ sustainable (direct) amide or peptide formation” is selected as one of the top research area in green chemistry. [1] To solve the problem, we are aiming to establish a method of electrochemical oligopeptide synthesis and recycle coupling reagents. Inspired by the report of Uribe’s group, [2] we selected triphenylphosphine (TPP) as the coupling reagent in electrochemical peptide bond formation. Although triphenylphosphine oxide (TPPO) is generated as the stoichiometric byproduct, reduction of TPPO to TPP are achieved in various ways. [3] Therefore, TPP can be a recyclable coupling reagent in peptide synthesis and this lead to reduce the amount of waste. In addition, we employed soluble tags as protecting group of carboxylic acids, which are consisted of benzyl group with long alkyl chain and precipitate in polar solvents, to make purification easier. [4] Until now, we have succeeded quantitative electrochemical peptide bond formation. Notably, we found that soluble tag serves to prevent undesired oxidation of amino acids maybe because long alkyl chain of soluble tag keep amino acids away from electrode. Work to synthesis bioactive oligopeptides is in progress.Reference[1] M. C. Bryan, P. J. Dunn, D. Entwistle, F. Gallou, S. G. Koenig, J. D. Hayler, M. R. Hickey, S. Hughes, M. E. Kopach, G. Moine, P. Richardson, F. Roschangar, A. Steven and F. J. Weiberth, Green Chem., 2018, 20, 5082-5103.[2] A. Palma, J. Cardenas and B. A. Frontana-Uribe, Green Chem., 2009, 11, 283–293.[3] Y. Okada, H. Suzuki, T. Nakae, S. Fujita, H. Abe, K. Nagano, T. Yamada, N. Ebata, S. Kim, and K. Chiba, J. Org. Chem., 2013, 78, 320−327.[4] D. Hérault, D. H. Nguyen, D. Nuel and G. Buono, Chem. Soc. Rev., 2015, 44 , 2508-2528. Figure 1