The Development of Novel Antibiotics Using ... - Jacobs University

Introduction
Figure 1.11 Synthetic route and dynamic reversibility of pyrazolotriazinones 48.
1.3.7 Michael addition
The 1,4-conjugate addition of a nucleophile to an α,β-unsaturated carbonyl compound is known
as Michael addition. The reaction is reversible at a pH of 7-8 and takes place at room
temperature in water making it suitable for different DCC applications. Addition of proteins or
biological targets is possible under such mild conditions. 50,51 Glutathione GSH-49 is a thiol
containing tripeptide existing in eukaryotic cells. It is an important antioxidant, which prevents
damage of cellular components caused by peroxides and other toxic electrophiles. It acts by
scavenging toxic electrophiles, enhancing their water solubility and thus eliminating them out
from the cell. Ethacrynic acid (EA) contains an α,β-unsaturated carbonyl functionality making it
suitable for the Michael addition reaction. Campopiano and co-workers reported on generation of
a DCL from GSH analogues 49-52 and EA 53 via Michael addition reaction (Figure 1.12).
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