KAT ligation is a rapid and highly chemoselective amide-bond forming reaction between acylborons and hydroxylamines. Although this reaction has attractive features for bioconjugation, it has not been applied to protein-protein conjugation due to the lack of synthetic methods for α-amino acylborons. Conventional preparation of acylboron possesses low functional group tolerance or requires many steps from readily available starting materials. Herein, we report the concise acylboron synthesis by the ozonolysis of alkenyl boronates. Ozonolysis of alkenyl MIDA (N-methyliminodiacetic acid) boronate 1a in the presence of pyridine in acetone at –78 oC afforded the desired acylboron 2a in 94% yield (Scheme 1). This method could be applied for the synthesis of various acylborons 2b–2f bearing various functional groups, such as chloride, ketone, benzyl ether and ester. We also achieved the first synthesis of α-amino acylboron including L-alanine type acylboron 2h in high enantiopurity. Furthermore, oligopeptide synthesis using α-amino acylborons revealed that amide-forming reaction proceed even in highly diluted aqueous media without epimerization at α-position under ligation conditions (Scheme 2).

Concise synthesis of acylboronates by ozonolysis and their application to oligopeptide synthesis

256th National Meeting (2018)

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