Discovery and application of 6π-azaelectrocyclization to natural product synthesis and synthetic biology

While elucidating the inhibitory mechanism of a hydrolytic enzyme by aldehyde-containing natural product, we discovered a reaction involving a rapid 6??-azaelectrocyclization of azatrienes generated from aldehyde with lysine residues. The electrocyclic reaction of the 1-azatriene system, a cyclization precursor, exhibited a significant substituent effect. Asymmetric chiral piperidine synthesis and a one-pot library synthesis of pyridines on solid-supports were applied to synthesize pyridine/indole alkaloid-type natural product. Additionally, we developed lysine-based labeling and engineering of biomolecules and living cells based on the rapid 6??-azaelectrocyclization. Both labels and oligosaccharide structures were introduced efficiently and selectively into surface lysines under the mild conditions; notable effects of N-glycans on proteins and living cells were visualized for the first time by PET and noninvasive fluorescence imaging.