Application of Intramolecular Migration Reaction in Peptide Chemistry to Chemical Biology, Chemical Pharmaceutics and Medicinal Chemistry

摘要

Nucleophilic reactions such as N-O/O-N intramolecular acyl migration in Ser- or Thr-containing peptides and succinimide formation in Asp derivatives by cleavage of ester or amide bonds are commonly used in Peptide Chemistry. These reactions are of great interest in Peptide Chemistry, Chemical Pharmaceutics and Medicinal Chemistry. In regard to O-N intramolecular acyl migration, new synthetic methods, designated as "O-acyl isopeptide methods" have been developed for making difficult sequence containing peptides, as well as for application as water-soluble prodrugs of HIV-1 protease inhibitors and anti-cancer drugs such as paclitaxel and other taxoid analogs possessing α-hydroxy-β-amino acid moieties. ! Moreover, new peptidic self-cleavable spacers that release a parent drug via succinimide formation in both water-soluble prodrugs and the oligoarginine-based cargo-transporter (OACT) system were developed as means to potentially enhance intestinal absorption of the parent drug.