Biomedical Engineering Reference
In-Depth Information
OTBS
CHO
Me(CH
2
)
6
1. ZnCl
2
, CH
2
Cl
2
, rt
2. aq. HF, MeCN
O
133
OH
O
+
+
Diastereomer
53%
OTBS
Me(CH
2
)
6
(CH
2
)
9
Me
Me(CH
2
)
9
135
(dr = 9.3:1)
SPy
134
136
, PPh
3
, DIAD
THF, 0°C to rt
88%
N
CO
2
H
OHC
136
O
H
N
O
OHC
O
O
Me(CH
2
)
6
(CH
2
)
9
Me
(-)-Panclicin D
137
O
H
O
OBn
O
138
ZnCl
2
, CH
2
Cl
2
, rt
+
OTBS
73%
OBn
140
(dr >19:1)
SPy
139
steps
O
O
O
8
HO
(8
S
/
R
)-Okinonellin B
141
SCHEME 9.25
Synthesis of panclicin D
137
and okinonellin B
141
by Romo and coworkers.
aldehyde in the presence of ZnCl
2
and HF to provide the enantiopure 2,3-
trans
-
b
-lactones
135
and
140
. In this case, the two domino reactions generating com-
pounds
result in a diastereomeric ratio of 9.3:1 and 19:1 in favor of the
trans
compounds, while the yields are 53% and 73%, respectively. For panclicin D
137
, cyclobutanone is required, and conversely in the synthesis of okinonellin B
141
135
and
140
-lactone moiety is used to produce enantiopure butyrolactone moiety
(Scheme 9.25).
One of the most recognized and commonly used analgesics, morphine, has been
a challenge for many synthetic chemists over decades. The benzyltetrahydroisoquino-
line alkaloid morphine (
,
b
) and the need for large quantities of this drug lend itself to
the efficiency of a domino-based synthetic approach. To this end, the Ogasawara
group has successfully completed a formal synthesis of (
150
)-morphine through a retro-
aldol/electrophilic aromatic substitution process (Scheme 9.26) [58]. The precursor
for this process is ketal
143
, which can be prepared from the chiral bicyclo[3.2.1]
octenone
142
. Treating the ketal
143
with ethylene glycol and
p
-TsOH in benzene
Search WWH ::
Custom Search