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OH
OH
O
OH
O
O
O
O
O
3
, CH
2
Cl
2
-78°C, 2 min
O
O
O
step
s
then thiourea, rt
78%
H
H
H
(-)-Penifulvin A
432
429
430
431
SCHEME 9.76
Mulzer and Gaich's synthesis of penifulvin A (
432
).
9.8.2. Domino Reactions Initiated by Reduction
Similar to the oxidative domino reactions, a reduction can be used as the first step in
a domino sequence, as shown in the synthesis of (
) that involved a
Staudinger reduction and an intramolecular aza-Wittig reaction (Scheme 9.77) [15].
Hence, upon treatment of the advanced enantiopure azide
)-stemonine (
31
with ethyldiphenylpho-
sphane, phosphineimide was generated with concomitant nitrogen evolution. This
intermediate then underwent a cyclization in an intramolecular aza-Wittig process to
form the seven-membered imine that was reduced using NaBH
4
to afford azepane
434
433
. The latter was then further manipulated to give (
)-stemonine (
31
).
) and the potential
for an efficient domino approach attracted Shibasaki and coworkers. In their enantio-
selective synthesis, the construction of the B and D rings occurred in a one-pot
process [170]. Hence, amination of the enantiopure alcohol
The structural complexity of the alkaloid (
)-strychnine (
185
435
using 2,2-bis
(ethylthio)ethylamine
436
led to the presumed intermediate
437
, which was then
treated with zinc in methanol and aqueous ammonium chloride to furnish the
teracycle
in 77% yield (Scheme 9.78). The mechanism is suggested to go
through initial reduction of the nitro group, 1,4-addition of the secondary amine,
and irreversible indole formation with the aniline moiety. The authors indicated that
this process eliminates the need for eight synthetic steps, which is an excellent
438
TBSO
TBSO
N
3
H
H
1. EtPPh
2
, Benzene, rt, 18 h
O
O
O
TBSO
2. NaBH
4
, MeOH, THF
NH
MeO
H
H
OMe
70%
OTBS
433
434
steps
H
H
O
N
H
O
H
O
O
H
(-)-Stemonine
31
SCHEME 9.77
Synthesis of stemonine (
31
).
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