The synthesis and reactivity of acylboron compounds have been actively studied. In particular, KAT (potassium acyltrifluoroborate) ligation, which is an amide bond forming reaction between KATs and hydroxyl amines, is one of the most unique reaction. This reaction proceeds rapidly without any condensation reagents under dilute conditions at room temperature. Although KAT ligation has suitable features for peptide-peptide conjugation, it has been difficult to synthesize α-amino acylborons and to introduce them to peptide C-terminal. Recently, we developed the novel synthetic method for α-amino acylborons via ozonolysis of alkenyl MIDA (N-methyliminodiacetic acid) boronates. Using this method, we investigated the synthesis of α-amino acylborons bearing hydroxyl amine moiety (HA-KAT) as an adaptor unit to introduce acylboron moiety to peptides. HA-KAT will be attached to peptide by KAHA (α-ketoacid-hydroxylamine) ligation between the hydroxyl amine at N-terminal of HA-KAT and the α-ketoacid at C-terminal of peptides. Although α-amino acid type HA-KAT could not be isolated due to its instability to moisture, dipeptide type HA-KAT was synthesized in high yield by ozonolysis of the corresponding alkenyl MIDA boronate. Then, we investigated the protection of the acylboron moiety prior to the deprotection of the hydroxyl amine moiety, and found that dithiol react with acylborons smoothly. In this study, we will report the synthesis of HA-KAT and its application to amide bond forming reaction.

Synthesis of α-amino acylboron bearing hydroxylamine moiety for preparation of peptides bearing acylboron moiety

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.