112
4 Applications of Nitrile Imine Derivatives
NH 2
O
O
OH
NH 2
O
OH
NH 2
H
N
O
OH
O
NH 2
H
N
O
OH
O
O
NH 2
H
N
O
OH
O
NH 2
H
N
O
OH
O
O
N
O
NH 2
H
N
O
OH
O
O
No activation
Electronic activation
Activation by strain
O
O
NH 2
H
N
O
OH
H
H
O
O
NH 2
H
N
O
OH
H
H
Scheme 4.10 A selection of different dipolarophiles ligated using NI cycloaddition following
genetic incorporation into a protein
N
H
O
Me
N
H
O
Me
N
H
O
Me
N
H
O
Me
N
N
Ph
MeO
N
O
N N
N
N
Ph
OMe
N
N
N
N
N
O
i.
ii.
BSA protein
BSA protein
R
R
Scheme 4.11 The differing reactivities of different cyclopropenyl isomers has enabled selective
orthogonal modification of different sites in proteins
transformation are discussed above (Sect. 2.4.2) and summarised in Table 2.2. In the
context of bioorthogonal photoclick chemistry, multiple reports have documented
the generation of NIs using longer wavelengths that present no harm to biomolecules
such as DNA [47–49].
Following the re-emergence of research into the reactivity of NIs towards nucleophilic additions (Sect. 4.2.2), more recent studies from Lin have investigated the