The Staudinger ligation is a method that has found increasing use in the growing field of chemical biology for labeling biomolecules, such as proteins, with fluorescent probes. Proteins possessing an azide functional group can be ligated onto a phosphine bearing the probe.

(a) Using your knowledge of the Staudinger reaction (Sec. 23.11A), propose a mechanism that accounts for the formation of a key intermediate in the Staudinger ligation, shown below.

(b) Instead of reacting with water to release the free amine, as in the Staudinger reaction, the probe-labeled protein product is formed. Draw a curved-arrow mechanism for the conversion of the intermediate in part (a) to the probe-labeled protein product in Fig. P23.81.

(c) In the absence of the methyl ester functional group, what would be the product of the reaction in the presence of water?

Transcribed Image Text:

probe O || C-OCH3 + P-N-protein Ph Ph