Biomedical Engineering Reference
In-Depth Information
N
N
H
H
Kopsifolines (
106
)
CH
2
CHO
OSiR
3
N
N
OH
CO
2
Me
CO
2
Me
R
R
110
109
O
O
N
N
CH
2
CO
2
Me
O
N
2
CH
2
CO
2
Me
O
O
O
N
N
H
CO
2
Me
CO
2
Me
R
R
107
108
SCHEME 13.25
The total synthesis of several members of the
vinca
and
tacaman
class of
indole alkaloids has recently been accomplished using push-pull dipoles in the
critical cycloaddition step [51]. The central step in the synthesis consists of an
intramolecular [3
-diazo indoloamide (i.e.,
111
)
that delivers the pentacyclic skeleton of the natural product in excellent yield
(Scheme 13.26). The acid lability of the oxabicyclic structure was exploited to
establish the
trans-
D/E ring fusion of (
þ
2]-cycloaddition reaction of an
a
)-3
H
-epivincamine
114
. Finally, a base-
induced keto-amide ring contraction was utilized to generate the E-ring of the
natural product. Avariation of the cascade sequence of reactions used to synthesize
(
)-3
H
-epivincamine
114
was also employed for the synthesis of the
tacaman
alkaloid (
)-tacamonine
115
.
In recent years, Boger and coworkers have developed a new synthetic approach
to the vinca alkaloids based on an intramolecular [4
2]-cycloaddition reaction
of 1,3,4-oxadiazoles that proceeds through a push-pull dipole [52]. This unique
domino cascade assembles the fully functionalized pentacyclic ring system of vindo-
line
120
in a single step that forms four C-Cbonds and three rings while introducing all
the requisite functionality and setting all six stereocenters within the central ring,
including three contiguous and four total quaternary centers. The reaction leading to
þ
2]/[3
þ
H
N
N
steps
HO
O
R
1
= H
R
2
= Et
MeO
2
C
Et
R
1
N
N
O
Rh(II)
(±)-3
H
-Epivincamine
114
N
N
R
2
O
O
O
O
R
1
N
2
steps
CH
2
R
2
CO
2
Et
EtO
2
C
H
R
1
= Et
R
2
= H
112
(R
1
= Et or H)
113
(R
2
= Et or H)
111
N
N
Et
O
H
H
(±)-Tacamonine
115
SCHEME 13.26
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