Biomedical Engineering Reference
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O
O
NaO
NaO
O
O
P
P
O
HO
O
OH
O
HO
O
OH
(+)-Cytostatine
76a
76b
O
O
NaO
NaO
O
O
P
P
HO
O
O
H
O
HO
O
H
76c
76d
FIGURE 10.2
(
รพ
)-Cytostatin
76a
and three stereoisomers
76b-76d
.
configurations were encoded by C
6
F
13
and C
8
F
17
tags, respectively (Scheme 10.18).
Compounds M-
83
contained two chiral centers and the configurations were encoded
by a regular alkyl (zero fluorine) and C
4
F
9
tag, respectively (Scheme 10.19).
The Horner-Wadsworth-Emmons reaction is a key step to couple M-
80
and
M-
83
to form M-
84.
Sequential 1,4-reduction using the Stryker reagent and ketone
reduction using LiAl(
t-
BuO)
3
H generated the sixth chiral center and gave M-
85
as a mixture of two pairs of quasi-racemic compounds, which were then converted to
M-
86
after several steps of reactions (Scheme 10.20). Since four compounds from two
O H
O
O I
F2
TIPS
F2
OTf
2,6-lutidin
e
72%
O
R
S
N
S
OPMB
N
OPMB
O
O
Bn
(
R,R,S,S
)-
77a
R
Bn
OTIPS
F2,F3
78a
LiBH
4
mix
HO
OPMB
77%
M-
79
O H
O
TIPS
F3
OTf
2,6-lutidine
92%
F3
O
I
O
R
S
N
OPMB
R
N
OPMB
O
O
steps
S
Bn
Bn
78b
OTIPS
F2,F3
(S
,S,R,R
)-
77b
CHO
TrO
TIPS
F2
= Si(
i
Pr)
2
CH
2
CH
2
C
6
F
13
TIPS
F3
= Si(
i
Pr)
2
CH
2
CH
2
C
8
F
17
M-
80
SCHEME 10.18
Synthesis of quasiracemic M-
80
.
OH
TIPS
F2
OTf
2,6-lutidin
e
80%
OTIPS
F0
R
R
TMS
TMS
OTIPS
F0,F1
O
O
(
R,R
)-
81a
82a
steps
MeO
P
mix
MeO
OH
OTIPS
F1
TIPS
F3
OTf
2,6-lutidin
e
91%
TMS
S
M-
83
S
TMS
TMS
(
S,S
)-
81b
82b
TIPS
F0
= Si(
i
Pr)
3
TIPS
F1
= Si(
i
Pr)
2
CH
2
CH
2
C
4
F
9
SCHEME 10.19
Synthesis of quasiracemic M-
83
.
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