Biomedical Engineering Reference
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SEt
Tf
2
O,
i-
Pr
2
NEt, then
EtS
SEt
OH
NH
NH
2
EtS
436
O
2
N
O
2
N
CH
2
Cl
2
, -78°C
O
O
H
H
OPMB
OPMB
OSEM
OSEM
435
437
Zn, MeOH
aq NH
4
Cl
77%
(2 steps)
EtS
N
EtS
H
N
steps
D
H
E
N
B
H
OPMB
H
O
H
H
O
OSEM
(-)-Strychnine
185
438
SCHEME 9.78
Synthesis of (
)-strychnine
185
by Shibasaki and coworkers.
illustration of the power of domino transformations. The synthesis of (
)-strychnine
185
(
) was eventually completed after an additional 11 synthetic steps.
Reissig and coworkers also reported a very elegant synthesis of strychnine using
a SmI
2
-mediated reduction/cyclization domino reaction [171].
The natural product (
) isolated from
Calystegia sepium
has been reported to possess glycosidase enzyme inhibition properties. Hence, it
selectively inhibits the rat liver
þ
)-calystegine B
2
(
441
-
D
-glucosidase and the human lysosomal galacto-
sidase Awith an IC
50
value of around 30mM. For the synthesis of (
b
þ
)-calystegine B
2
(
), Hanna and Boyer [172] employed a triple domino procedure first discovered by
Madsen and Hyldtoft [173] in their synthesis of aminocyclohexenes. In the total
synthesis of the polyhydroxylated nortropane alkaloid
441
441
, the 6-iodoglucopyranose
439
-
D
-glucopyranoside, was treated
with zinc dust and benzylamine followed by the addition of allyl bromide to afford the
amino diene
, easily accessible from inexpensive methyl-
a
in 73% yield and in a 85:15 diastereoisomeric ratio (Scheme 9.79).
In this reaction sequence, the aldehyde intermediate, supposedly formed after zinc
reduction, reacted with benzyl amine followed by allyl bromide to generate the diene
440
440
, which then was treated with Grubbs catalyst to afford the corresponding
N
OH
Zn, ))), THF, BnNH
2
then allyl bromide
O
OMe
OH
BnO
steps
I
H
73%
BnO
OBn
OH
OH
BnO
NHBn
OBn
OBn
439
440
(dr = 85:15)
(+)-Calystegine B
2
441
SCHEME 9.79
Hanna and Boyer's synthesis of calystegine B
2
(
441
).
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