Chemistry Reference
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TABLE 10-2. In Vitro Cytotoxicities Against Cancer Cells by Asiminocin
and Other bis-THF Acetogenins
H-116 (Marshall
HT-29 (MacLaughlin
et al.'s results)
et al.'s results)
Compound
IC
50
(mg/mL)
IC
90
(mg/mL)
IC
90
/IC
50
IC
50
(mg/mL)
5
10
3
<
10
12
Asiminocin
a
1.5
300
Asimicin
a
5
10
4
2
10
3
<
10
12
4
Dihydroasimicin
a
2
10
4
1
10
1
500
Asimin
a
3
10
4
3
10
3
<
10
12
10
Bullanin
a
3
10
3
1
10
1
5
10
12
33
5-Fluorouracil
b
1.5
10
1
1.5
10
a
1 g/mL
1.5 M.
b
1 g/mL
7.0 M.
activities were more potent than that of 5-fluorouracil, a drug currently used for
cancer chemotherapy. However, the Marshall et al. data are 10
8
-10
9
less potent
than those reported previously by McLaughlin et al. by the same compounds. Addi-
tionally, the dihydroasimicin exhibited similar activities as asimicin, although its
double bond of terminal lactone was saturated.
Elegant combinations of Sharpless dihydroxylations/epoixdation and Mitsunobu
reaction on the unsaturated fatty acids were developed by Keinan et al., in con-
structing various THF rings in the syntheses of uvaricin,
55
squamotacin,
56
and tri-
lobin.
57
Scheme 10-21 shows the syntheses of squamotacin and trilobin. During the
course of converting g-unsaturated lactone 104 into epoxide 108, Sharpless dihy-
droxylations (AD-mix-a, AD-mix-b) were used twice and Sharpless epoxidation
was used once. Epoxide opening of 108 with alkyne generated the phosphorium salt
109, which was used for the following Wittig reaction to establish the whole
skeleton. After two steps of routine transformations, squamotacin was finally
synthezied. The synthesis of trilobin with threo-trans-erythro-trans-threo bis-THF
configuration also used these two reactions as key steps. However, establishment of
its skeleton used the epoxide opening reaction by a terminal alkyne. While synthe-
sizing bullatacin and asimicin,
58
Re
2
O
7
-mediated oxidation of homoallylic alcohols
was used as the key reaction.
Re
2
O
7
-mediated tandem oxidative polycyclization of polyenic bis-homoallylic
alcohols was also developed by Keinan et al. in their synthesis of bis-THF aceto-
genins. Several important conclusions were drawn on Re
2
O
7
-mediated oxidations
of ployalkene: (1) The first THF ring formed is always in trans-configuration. (2)
If two oxygenated functional groups existing in the above THF containing inter-
mediate are in threo-configuration, the next forming THF ring will be a cis one;
otherwise, a trans-THF will form. These rules are well used in their synthesis of
rollidecin C and rollidecin D
59
(Scheme 10-22). Epoxide 115 preapred by Sharpless
AE was selectively reduced by Red-Al to give 1,3-diol, and then this diol was con-
verted into the phophorium salt 116. Wittig reaction of aldehyde 117 or 118 with
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