Biomedical Engineering Reference
In-Depth Information
O
O
O
O
OTBS
OTBS
K
2
CO
3
, Dioxane
HO
O
125°C, 12 h
H
H
95
96
O
O
OH
H
OTBS
O
OTBS
O
H
H
98
97
OH
O
OH
O
OH
Me
HO
N
H
O
H
H
Me
2
N
H
O
(+)-Cortistatin A
99
Prednisone
100
SCHEME 9.18
Synthesis of cortistatin A
99
by Nicolaou and coworkers.
Several excellent approaches to camptothecin
have been published [41], a quite
new access developed by Yao and coworkers [42] used a domino Michael/aldol
reaction, a sequence that belongs to the most versatile domino processes. Thus,
reaction of
ortho
-aminobenzaldehyde
(101)
in
the presence of pyrrolidine and benzoic acid followed by oxidation with MnO
2
gave
quinoline
102
with the
,
-unsaturated aldehyde
103
a
b
can be
assumed. Further transformations including a hetero-Diels-Alder reaction of an
1,3-oxabutadiene and a Sharpless bis-hydroxylation to introduce the stereogenic
center with the hydroxy group led to
104
in 75% yield. In this process, the intermediates
105
-
107
101
(Scheme 9.19).
was isolated from
Penicillium diversum
and structurally
identified by Turner in 1978 [43a]; its absolute configuration has recently been
determined by Krohn [43b]. The compound belongs to the group of mycotoxins
as secondary metabolites from fungi and show diversified biological activities
[44]. Brase and coworkers developed the first total synthesis of racemic diversonol
using a domino oxa-Michael/aldol reaction [45a,b], and the first enantioselective
total synthesis of
Diversonol
(108)
108
has recently been accomplished by Tietze and coworkers
using a domino Wacker/carbonylation process [45d].
For the synthesis of
rac
-
,Brase and coworkers constructed the xanthenone
skeleton of
108
by treating a mixture of aldehyde
109
and cyclohexenone
110
with
imidazole as base to give
108
in 61% yield (Scheme 9.20). Further transformations
allowed the introduction of the methyl group at C4a in
111
111
to end the process.
Boeckman et al.
[46] described an enantioselective total synthesis of
(
þ
)-tetronolide (
112
), which is a member of a group of aglycones of the naturally
Search WWH ::
Custom Search