Chemistry Reference
In-Depth Information
SCHEME 11.21.
thermochemical reaction of AFQ with several heterocyclic amines (Scheme 11.21)
for the preparation of novel 7-hydrazino-1-ethyl-6,8-difluoroquinolone-3-carbox-
ylate derivatives.
62
We extended our experimental studies to investigate the
photochemistry of AFQ.
63
In diethylamine, we obtained a hydrazine derivative
in good yield.
64
The mechanism for both reactions (thermolysis and photolysis) is quite similar
involving a highly reactive singlet nitrene. In the photolytic reaction mixture, a small
amount of 7-amino-1-ethyl-3-carboxylate-6,8-difluoroquinolone was also obtained.
This latter compound is most likely due to triplet nitrene reaction with C
H bond in
the solvent. A triplet nitrene could be generated by means of an ISC mechanism
induced by the presence of the ketone group in the azide.
63
11.7 PHOTOAFFINITY LABELING AND BIFUNCTIONAL
PHOTOCHEMICAL PROBES
Understanding the mechanisms involved in the photochemically induced insertion
reactions of aryl nitrenes on hydrocarbon and amine solvents
12
have led to a renewed
interest in the development of new synthetic photoprobes for PAL.
6,8,10,65-68
Modifications of bioactive molecules by photochemical methods find applications
in bifunctional cross-linking of biomolecules,
69-72
topological mapping of receptors
binding sites,
73
electron microscopy,
74
modification of surfaces,
75-77
and labeling of
macromolecules.
5,78
In a classical PAL experiment, a natural ligand is derivatized to incorporate a light
sensitive moiety that serves as a precursor for a highly reactive intermediate that may
form a new covalent bond with a biomolecule.
78-81
In this experiment, low
efficiencies in photocovalent attachment are sufficient to identify some binding
sites of receptors.
The success of PAL depends on the formation of a strong covalent bond in the near
vicinity of binding site of the receptor and this bond must be stable to survive
analytical procedures (proteolysis) to obtain chemical information about functional
groups and stereochemistry in receptor site.
10,65
