2019 年 77 巻 9 号 p. 904-911
In drug discovery, various biologically active peptides have been discovered, characterized and modified for medicinal chemistry. However, the utilization of peptides as therapeutics has some limitation owing to several factors, including low metabolic stability towards proteolysis and undesired interactions with multiple receptors. Hence, the development of “peptidomimetc”, in which a part or whole of a molecule is modified, is an important strategy with which to enhance the stability or bioactivity of peptide-based drugs. In this situation, we have designed and developed a synthetic method for chloroalkene dipeptide isosteres (CADIs), which involves replacement of an amide bond in peptides with a chloroalkene structure, toward the peptidomimetc. By a developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained utilizing diastereoselective allylic alkylation with organocopper reagents as a key reaction. This CADI was also transformed into an N-Fmoc protected CADI in a few steps. In addition, The CADI could be used in Fmoc-based solid-phase peptide synthesis and applied to introduce for a bioactive peptide.