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(b)
(a)
2,3
β
3
β
R
O
R
O
Fmoc
R
O
Fmoc
H
OH
H
OH
H 2 N
OH
Arndt-Eistert
homologation
Kolbe
reaction
Davies
Method
R
O
O
O
R
R
Li
PG
PG
LiO
O
X
OMs
R
OR
R
OR
H
H
R
OR
O
+
+
MeX
+ CH 2 N 2
+ KCN
L N
Ph
Ph
activated α -amino acid
from reduction of
α
-amino acid
(c)
2
β
R
H 2 N
OH
O
Curtius
degradation
Evans
methodology
O
O
R
BnO 2 C-CH 2 I
R
HOOC
N
COOR
O
Ph
+ (PhO) 2 PO-N 3
Ph
+ PG-NH-CH 2 X
Figure 2.4 three generally applicable methods for the preparation of various types of
b-amino acids with 21-proteinogenic side chains (R-).
additions [23]. The synthetic methods are so many that it is impossible to provide an
exhaustive number of examples to show the state of the art (some examples are shown in
Figure 2.5). Many other examples are reported in a review recently published by Feringa
et al. [24].
Cyclic b-amino acids have a broad range of use as building blocks for the preparation
of modified analogues of biologically active peptides. In cyclic b-amino acids, the amino
and carboxyl functions are situated on neighboring atoms, thus these compounds can exist
as R or S isomers, with a total of four possible enantiomers. The availability of a vast
number of stereo- and regio-isomers, together with the possibility of ring size expansion
and further substitutions on the ring, significantly extends the structural diversity of
b-amino acids, thereby providing enormous scope for molecular design. Several methods
have been developed for the synthesis of enantiomerically pure cyclic b-amino acids [30].
Figure 2.6 shows some examples that can help us to demonstrate how many methods may
be used to prepare these compounds.
b-Peptides fold to helices or hairpin-type structures, and they can be constructed such
that they do not fold but are linear or assemble to pleated sheets. In contrast to their natu-
ral a-peptidic counterparts, b-peptides form such secondary structures in protic solutions
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