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could be labeled with alkynyl tags by treating them with
(1,3)FucT and GDP-6-
alkynylfucose (GDP-FucAl), and detected by BTTES-promoted CuAAC [67].
8.4 STAUDINGER LIGATION
The Bertozzi group disclosed the first example of the use of azide as a chemi-
cal reporter by exploiting a modified Staudinger reaction. The Staudinger reaction
between an azide and a phosphine proceeds smoothly in water to give a primary
amine and the corresponding phosphine oxide (Scheme 8.2a) [68]. To avoid hydrol-
ysis of the aza-ylide intermediate of the Staudinger reaction, a phosphine reagent
was designed that contains a strategically placed ester functionality, which serves
as an electrophilic trap to capture the nucleophilic aza-ylide intermediate by an
intramolecular cyclization, leading to the formation of a stable amide bond (Scheme
8.2b) [44]. The usefulness of this reagent for bioorthogonal chemistry was demon-
strated by metabolic labeling of Jurkat cells with Ac
4
ManNAz (20 mM) for 3 days
to install azido-containing cell surface glycoconjugates. The latter moieties could
be reacted with a biotinylated phosphine reagent and the resulting reaction products
could be visualized by staining with fluorescein isothiocyanate-labeled avidin (FITC-
avidin). The azido-labeled cells showed a marked increase in fluorescence intensity
when reacted with phosphine (1 mM) compared to cells that were not exposed to
R
(a)
N
N
N
H
2
O
NH
2
N
P
R
+
+
P
R
R
R
R
N
2
R
(Aza-ylide)
O
P
R
R
(b)
N
N
N
Ph
Ph
N
P
+
MeO
Ph
2
P
TAG
MeO
N
2
O
TAG
O
electrophilic trap
O
Ph
OMe
Ph
Ph
2
P
H
2
O
P
N
NH
-MeOH
TAG
TAG
O
O
SCHEME 8.2
(a) Staudinger reaction between azides and phosphines; (b) Staudinger liga-
tion of azides with triarylphosphines.
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