Chemistry Reference
In-Depth Information
CO
2
Et
O
O
O
O
TMG (
3
)
OH
OAc
NO
2
THF
15
O
2
N
AcHN
+
80-87%
CHO
HO
AcO
17
18
OHC
16
2. DCC, DMAP
3. AcCl, DMAP
70%
(3 steps)
1. 1.2 N HCl
OAc
pig liver
esterase, pH 7
14 d
OAc
O
H
O
H
87%
(93% ee)
O
H
O
HO
AcO
20
Kishi lactam (
21
)
19
ref. 36
Me
OH
Me
H
perhydrohistrionicotoxin (
22
)
Scheme 7.2
Synthesis of a key intermediate 21 of perhydrohistrionicotoxin (22)
The double Henry reaction was examined by Luzzio and Fitch for the synthesis of a key
intermediate 21 of perhydrohistrionicotoxin (22) [3]. Reaction of nitroalkane 15 and
glutaraldehyde 16 using TMG (3) in dry tetrahydrofuran (THF) proceeded via a double
nitroaldol reaction to give meso-17 in 80-87% yield. After conversion of the diol to meso
lactamdiacetate 19, esterase mediated hydrolysis gave optically active 20 in 87%yield with
93%ee (Scheme 7.2). This hydroxyacetatewas successfully led to the Kishi lactam (21) [4],
a key intermediate for 22.
Madin et al. reported a synthesis of gelsemine (28) [5] in which a DBU promoted
skeletal rearrangement reaction was applied. Treatment of 23 with DBU in refluxing
toluene proceeded through a retro aldol-aldol reaction process with epimerization at C3,
and the resulting axial alcohol 25 cyclized at the nitrile group to generate lactone 27 after
hydrolysis of the imidate 26. The lactone 27 was successfully converted to gelsemine (28)
(Scheme 7.3).
