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OH
a,b
O
N
H2N N
Boc
N 3
H
N R
N
N
H2N N N
N
H
a) i : (COCl) 2,CH 2Cl 2, DMF (cat.), ii : CH 2N 2,Et 2O/CH 2Cl 2, iii : HBr (82%) ; b) Boc-guanidine, DMF, RT
(59%) ; c) azide, CuSO 4, Na ascorbate, EtOH, CH 2Cl 2,H 2O; d) TFA, CH 2Cl 2 (58-94 % over two steps)
Scheme-1.11.1 Melander’s 2-AI-T conjugate synthesis.
It was explained by earlier work that once target 2-AI alkyne had been synthesized,
assembled a diverse array of azido amides to employ in the click reaction to create
pilot collection of 2-AIT conjugates. Briefly, 2-bromo-ethylamine was treated with
sodium azide to deliver 2-azido-ethylamine, which following acylation (via the
respective acid chloride) generated the azido amides for elaboration into the 2-AIT
collection. Each azido amide was then subjected to the click reaction with target 2-AI
alkyne. Boc-deprotection (TFA/CH2Cl2) followed by counterion exchange
(trifluoroacetate for chloride) delivered the target 2-AIT compounds for antibiofilm
screening.
1.12 Introduction to Biofilm
Biofilms play a significant role in infection disease and account for up
to 80% of microbial infections in the body.
Bacterial biofilms are defined as a surface-attached community of bacteria
that are surrounded by a protective extracellular matrix.
On a global scale, biofilm related costs incur 6-10 billions of Euros to the
agricultural, engineering, and medical sectors of economy.
Despite the focus of modern microbiology research on pure culture,
planktonic bacteria, it is now recognized that most bacteria found in
natural, clinical, and industrial settings persist in biofilms.
Within a biofilm, bacteria are upward of 1000-times more resistant to
conventional antibiotic treatment
Biofilms grow virtually everywhere, in almost any environment where
there is a combination of moisture, nutrients, and a surface.
c,d
H N
R