Chemistry Reference
In-Depth Information
HO
NH
2
(a)
Me
O
Me
OH
OH
Halogen-Exchange/
Dehalogenation
O
AA2 and AA6
CH
2
OH
O
O
AA2 and AA6
Cl
Mutasynthesis
O
O
Cl
HO
OH
O
O
H
N
H
N
H
N
N
H
NH
O
AA7
H
H
H
H
O
O
NHMe
Edman
degradation/
Acylation
O
O
H
H
AA1
NH
2
R
HO
2
C
OH
OH
HO
Hydrolysis/
Amidation
AA3
AA7
Mannich reaction
Deglycosylation/
Glycosylation
Carbohydrates
Alkylation
Acylation
HO
(b)
NH
2
Me
O
Me
OH
O
O
n
OH
Cl
O
O
O
Cl
HO
CH
2
OH
OH
O
O
Cl
O
O
Cl
C
-Terminus
Amidation
Esterification
HO
OH
O
O
H
N
H
N
H
N
N
H
NH
O
H
H
H
H
N
-Terminus
Alkylation
Acylation
O
NHMe
H
O
O
O
H
NH
2
HO
2
C
OH
OH
HO
Scheme 2-9. Semisynthetic modifications of vancomycin-type glycopeptide antibiotics. (a)
Alterations and modifications of amino acids. (b) Attachment of molecules to the amino
groups,
to
the
carboxy
groups,
and
to
phenolic
carbohydrate
functionalities.
Similar
modifications have been performed for antibiotics of the teicoplanin-type.
easily modifyable functional groups, for example, amino and carboxy groups.
However, over the past few years, chemists have introduced more sophisticated mod-
ifications that are closer to the D-Ala-D-Ala binding pocket. As a consequence of the
understanding of glycopeptide biosynthesis over the recent years, biotechnological
approaches have been performed. One example is mutasynthesis,
98,99
which is the
feeding of modified amino acid building blocks to glycopeptide producer mutants,
which results in a restored production of altered glycopeptide antibiotics. In the
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