Biomedical Engineering Reference
In-Depth Information
O
1. Pyrrolidine
benzoic acid
CH
2
Cl
2
, rt
O
CHO
H
H
+
2. MnO
2
, CH
2
Cl
2
NH
2
N
75%
OAc
OAc
102
103
104
PhCOOH
PhCOO
O
N
OH
N
O
H
N
H
H
H
OAc
OAc
OAc
105
106
107
O
N
N
O
101
OH
O
SCHEME 9.19
Synthesis of camptothecin
101
by Yao and coworkers.
occurring tetrocarcins [47]. These compounds, which contain a spirotetronic acid
moiety, have a wide range of biological activities that include antibiotic properties
against some Gram-positive microorganisms, anticancer activity against sarcoma
180, leukemia, and melanoma, and a selective inhibition of mitochondrial func-
tions [48]. One of the key steps in their synthesis of (
þ
)-tetronolide (
112
) involved the
addition of alcohol
113
to an
-keto ketene formed intermediately from dioxinone
a
114
. The resulting product acted as a potent dienophile in an intramolecular Diels-
Alder reaction. Thus, reaction of
in a sealed tube at 140
C led to the
113
and
114
desired
-ketoester
115
in 69-97% yield as a single diastereomer (Scheme 9.21).
b
odeker in
1881 [49]. It shows several beneficial medicinal properties and has been the target
of has been the target of several syntheses, however, so far all these approaches led to
the racemic compound. The group of Carter [50] published the first enantioselective
synthesis of
Lycopodine (
122
) is a natural alkaloid that was isolated by B
€
using a domino process that follows a strategy inspired by
Heathcock et al. [51] The first step is the formation of an iminium ion in substrate
122
Imidazole
Dioxane/H
2
O
sonication, 7 day
s
61%
OMe
O
OH
O
OH
OH
OMe O
O
H
+
4a
O
O
OH
H
OH
OH
OH
110
108
109
111
SCHEME 9.20
Racemic synthesis of diversonol
108
by Brase and coworkers.
Search WWH ::
Custom Search