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NH
2
HO
HO
OH
O
OH
O
NH
2
O
NH
2
N
N
HO
O
O
N
N
O
OH
N
NH
2
N
O
O
OH
R
O
O
OH
NH
2
25
O
OH
O
H
2
N
OH
R = alkyl
26
O
O
O
O
N
N
N
N
OBn
N
R
HO
OBn
N
(CH
2
)
7
CH
3
R = n-octyl, pyridyl
2
2
FIGURE 12.11
Antifungal and Antibacterial triazolyl glycoconjugates.
for the synthesis of numerous glycosylated analogs with the anticipation of better
therapeutic index. Walsh and Lin derived Tyc analogs containing mono-, di-, and tri-
propargyl glycines using a chemoenzymatic peptide coupling approach. A subsequent
click reaction with a library of 21 azido sugars afforded 247 carbohydrate-modified
tyrocidine analogs. Screening of all the compounds for minimal inhibitory concen-
tration (MIC) and minimal hemolytic concentration (MHC) index demonstrated the
6-times better therapeutic index of triazole-grafted glycopeptides (
29, 30
) than natural
tyrocidine (Tyc) (Fig. 12.12) [55].
Vancomycin, a glycosylated natural product from
Amycolatopsis orientalis,
is a
last defense against infections caused by methicillin-resistant Gram-positive bacteria,
such as
Staphylococcus aureus
or
Enterococcus faecium
. It inhibits cell wall synthe-
sis in Gram-positive bacteria by binding to D-Ala-D-Ala. Thorson et al. applied
chemoenzymatic and click approach for the synthesis of a library of diverse mono-
glycosylated Vancomycin variants. All the derivatives were assessed, and deriva-
tive (
32
) registered twice enhanced antibacterial activity against both
S. aureus
and
E. faecium
while being only one-half as potent as vancomycin against
B. Subtilis
(Fig. 12.13) [56].
12.5.4 Antiviral Activities
Monovalent and multivalent sialic acid containing scaffolds modified at
C
-4 or
C
-
7 positions serve as highly potent biologically active molecules [57]. Jiang et al.
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