Biomedical Engineering Reference
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Ph
Ph
O
O
5
(2 mol%)
Ph
2
C
N
O
t
-Bu
Ph
2
C
N
O
t
-Bu
+
PhCH
2
Br
H
H
50% KOH aq
Toluene, 0°C
O
O
Ph
32
DL
-
33
TBAB
(
S
,
S
)-
5c
(
R
,
R
)-
5c
(
S
,
S
)-
5e
(
S
,
S
)-
5f
(
S
,
S
)-
5g
; 85% (de = 8%)
; 88% (de = 55%)
; 83% (de = 20%)
; 43% (de = 81%)
; 93% (de = 86%)
; 97% (de = 97%)
Ar
-
Br
+
N
Ar
(
S
,
S
)-
5c
(
S
,
S
)-
5e
(
S
,
S
)-
5f
(
S
,
S
)-
5g
(Ar = -Naphth)
(Ar = 3,4,5-F
3
-C
6
H
2
)
(Ar = 3,5-(
t
-Bu)
2
-C
6
H
3
)
(Ar = 3,5-(3,5-(
t
-Bu)
2
-C
6
H
3
)
2
-C
6
H
3
)
SCHEME 7.15
Ph
Ph
Ph
Ph
PhCH
2
Br
(
S
,
S
)-
5g
(2 mol%)
50% KOH aq
Toluene
0°C, 2 h
90%
SCHEME 7.16
O
O
O
O
N
N
Ph
2
C
N
O
t
-Bu
Ph
2
C
N
O
t
-Bu
H
H
H
H
O
CH
3
O
O
CH
3
O
Ph
DDL
-
34
DDDL
-
35
(de = 94%)
the corresponding protected tetrapeptide
DDDL
-
35
was obtained in 90% yield with
excellent stereochemical control (94% de) (Scheme 7.16) [42].
Ooi and coworkers developed a novel method for the synthesis of peptides
containing quaternary stereogenic carbon centers.
C
-Terminal azlactone
36
derived
fromdipeptide underwent stereoselective alkylation with high efficiency by the use of
a chiral tetraaminophosphonium salt
27
as a phase-transfer catalyst, and the alkylated
azlactone product
37
could be employed directly for peptide ligation to give growing
peptides such as
38
(Scheme 7.17) [43].
7.3. MICHAEL ADDITION
The asymmetric Michael addition of active methylene or methine compounds to
electron-deficient olefins, particularly
-unsaturated carbonyl compounds, repre-
sents a fundamental yet useful approach to construct functionalized carbon frame-
works. Enantioselective Michael addition of glycine derivatives by means of chiral
phase-transfer catalysis has been developed to synthesize various functionalized
a
,
a
b
-amino acids. These results are summarized in Table 7.3.
The Michael addition of glycine derivatives was applied to the efficient
asymmetric synthesis of pyrrolidine, hexahydropyrrolizine, and octahydropyrrolizine
core structures [48]. Treatment of
2c
with an
a
,
b
-enone
42
under phase-transfer
conditions in the presence of (
S
)-
41a
gave the corresponding Michael adduct
43
.
Intramolecular
-alkyl
a
reductive amination of
43
and subsequent acetal hydrolysis
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