Peptide therapeutics have witnessed a renaissance over the past decades.[1] The immense growing need for large-scale production of peptides as drugs requires manufacturing peptides at reasonably low prices. In addition, the impurities caused by over activation of conventional coupling reagents have become a major concern for peptide drug manufacture.[1] However, current peptide synthesis methods and strategies are mainly relied on the reagents and technologies developed in 1950-1970s, and are reaching a high standard and their inherent limits. Highly efficient novel methodologies to solve these bottleneck problems are in great demand. In such context, the use of structure well defined active esters, which simplifies peptide bond formation mechanism and avoids undesired side reactions, represents an attractive alternative method.[2] Our group is interested in the development of easily prepared active esters for peptide synthesis.[3] Herein, we report a kind of novel vinyl esters, both their preparation and the subsequent aminolysis proceed spontaneously. Note that the aminolysis reaction completes in few minutes to furnish amide in quantitative yield.[4] Importantly, this chemistry can be used for peptide bond formation in a racemization-free manner. Our result demonstrated that such vinly esters not only are amenable to dipeptide synthesis and peptide segment condensation but also work well for solid phase peptide synthesis.
References:
[1] Zompra A. A., Galanis A. S., Werbitzky O., Albericio F., Future Med. Chem. 2009, 1, 361-377.
[2] Bodanszky M., Bednarek M. A., J. Protein Chem. 1989, 8, 461-469.
[3] a) Hu L., Xu S. L., Zhao Z. G., Zhao J. F., J. Am. Chem. Soc., 2016, 138, 13135–13138; b) Yang J. H., Wang C. L., Xu S. L., Zhao J. F., Angew. Chem. Int. Ed. 2019, 58, 1382-1386.
[4] Wang Z. N., Wang X. W., Zhao J. F., J. Am. Chem. Soc. 2021, 143, 10374-10381.