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