Staudinger reaction using 2,6-dichlorophenyl azide derivatives for robust aza-ylide formation applicable to bioconjugation in living cells

Abstract

Efficient formation of water- and air-stable aza-ylides has been achieved using the Staudinger reaction between electron-deficient aromatic azides such as 2,6-dichlorophenyl azide and triarylphosphines. The reaction proceeds rapidly and has been successfully applied to chemical modification of proteins in living cells.

Multifluorinated Aryl Azides for the Development of Improved H2S Probes, and Fast Strain‐promoted Azide‐Alkyne Cycloaddition and Staudinger Reactions

“…Hosoya and co‐workers also reported a Staudinger reaction between electron‐deficient aryl azides and triarylphosphines . The kinetic studies indicated that the Staudinger reaction rate of 2,6‐dichlorophenyl azide toward phosphine in acetonitrile‐ d 3 was 0.63 M −1 s −1 .…”

“…Hosoya and co-workers also reported a Staudinger reaction between electron-deficient aryl azides and triarylphosphines. [24] The kinetic studies indicated that the Staudinger reaction rate of 2,6-dichlorophenyl azide toward phosphine in acetonitrile-d 3 was 0.63 M À 1 s À 1 . Additionally, the reaction was applied for cell surface-specific fluorescent labeling via the expression of transmembrane domain-fused HaloTag protein, which was further treated by 19 and 20 (Figure 10b).…”

“…[23] Clearly, the reduction of aryl azides via the Staudinger reaction using triphenylphosphine is difficult to process in organic synthesis. [24] From another point of view, such nonhydrolysis Staudinger reaction (NSR) may be considered as a new bioconjugation strategy.…”

“…Additionally, the Staudinger reaction of aryl azides and aryl phosphines is distant from that of aliphatic phosphines (Figure ), where the iminophosphorane is stable enough to resist hydrolysis and the product of classic Staudinger ligation is hard to detect . Clearly, the reduction of aryl azides via the Staudinger reaction using triphenylphosphine is difficult to process in organic synthesis . From another point of view, such nonhydrolysis Staudinger reaction ( NSR ) may be considered as a new bioconjugation strategy.…”

“…(b) Chemical modification of an azido-protein using the Staudinger reaction. Reprinted with permission from ref [24]…”