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inspired library was constructed utilizing click chemistry to generate a diverse library
of 2-aminoimidazole/triazole conjugates (2-AIT).These compounds displayed the
widest spectrum of anti-biofilm activity observed within the 2-aminoimidazole class
(Fig. 1.11.7). 120-121
H 2N
H 2N
N
N
H
N
Bromoageliferin
H 2N
N
N
H
NH
HN
Br
N
H
N
H
O
O
NH
O
Oroidin
H
N
H
N
Br
Br
Br
Br
H 2N
N
N
H
H 2N
HN
N
N
H
O
H
N
H
N O
Br
NH
Br Br
Br
H 2N
H 2N
N
N N
R
2-AIT Library
N
N
H
N
N
H
TAGE
CAGE
Fig. 1.11.7 Representative 2-aminoimidazoles derived from the marine natural
products bromoageliferin and oroidin.
The synthetic approach to this 2-AIT derivatization is outlined in (Scheme 1.11.1). In
their previous synthesis of 2-AIT conjugates, they employed the alkyne-derived 2-AI
as a precursor for the CuI-mediated[3+2] alkyne/azide cycloaddition (click reaction).
Although this reaction worked well, purification of the resulting product was
cumbersome, due to the need for copious amounts of ammonia saturated methanol for
column chromatography. Therefore, they decided to revise the route by employing a
Boc-protected 2-AI alkyne that would allow more traditional means of purification
(i.e. methanol/dichloromethane columns). The Boc-protected scaffold was
synthesized from oct-7-ynoic acid by treatment with oxayl chloride followed by
diazomethane and quenching of the resulting α-diazo ketone with HBr to generate the
intermediate a-bromo ketone. Cyclization with Boc-guanidine then delivered the
target 2-AI alkyne..
NH 2
NH 2
NH 2
NH 2