Organic Letters
Letter
REFERENCES
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=
1.24 ± 0.19 μM, Figure S1) to that previously reported for
(
1) Carroll, A. R.; Nash, B. D.; Duffy, S.; Avery, V. M.
Albopunctatone, an Antiplasmodial Anthrone-Anthraquinone from
the Australian Ascidian Didemnum albopunctatum. J. Nat. Prod. 2012,
1
the ascidian-derived material.
Given the common ancestry of plants and Plasmodium
3
7
species, and the demonstrated herbicidal activity of some
7
5, 1206−1209.
3
8
antimalarials, the effect of albopunctatone on Arabidopsis
observed up to 100 μM (Figure S2). This result could reflect a
biological target only expressed in the parasite, and thus likely
outside the apicoplast, or simply poor uptake in the plant.
Thus, the intriguing biological target of albopunctatone
remains unknown. Given the potent and highly selective
antimalarial activity of the AAQs, further studies to elucidate
this target are warranted. The syntheses presented herein
provide the means to obtain the necessary materials to
interrogate the mode of action of the AAQs.
(2) Previously isolated AAQs sharing the same backbone (Figure 1,
highlighted blue) as albopunctatone have been numbered incon-
sistently. In some cases AAQs are numbered such that the
4
,5,9
anthraquinone and anthrone units are C7−C10′ linked,
and in
3
,6−8
others they are considered to be C10−C7′ linked.
The system
10
employed by Hou et al. to number scutianthraquinones A−D was
applied to albopunctatone.
(
3) Yagi, A.; Makino, K.; Nishioka, I. Studies on the Constituents of
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ASSOCIATED CONTENT
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Anthraquinone Dimers from Aloe Elgonica. J. Nat. Prod. 1990, 53 (5),
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1
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and C NMR spectra; antiplasmodial results; herbicidal
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AUTHOR INFORMATION
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*
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D.; Brodie, P. J.; Goetz, M.; Cassera, M. B.; Kingston, D. G. I.
Isolation of antiplasmodial anthraquinones from Kniphofia ensifolia,
and synthesis and structure−activity relationships of related
compounds. Bioorg. Med. Chem. 2014, 22, 269−276.
The authors declare no competing financial interest.
39
Biological assays against L. donovani amastigotes, T. cruzi
4
0
39,41
43
amastigotes, T. b. brucei,
P. falciparum 3D7 asexual
3
9,42
39
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parasites,
M. tuberculosis, and HEK-293 cells were
conducted as described previously.
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ACKNOWLEDGMENTS
Glycosylanthraquinone Synthesis: Total Synthesis of Vineomycinone
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B2Methyl Ester. J. Am. Chem. Soc. 1991, 113, 5775−5783.
We thank the UWA Centre for Characterisation, Microscopy
and Analysis, in particular Drs. Gareth Nealon and Michael
Clarke, for assistance with NMR spectroscopy and mass
spectrometry, respectively. G.A.P. is the recipient of an
Australian Postgraduate Award. A.P.W. was an undergraduate
student on exchange from Bristol University at the time. M.S.
is the recipient of a Griffith University Postdoctoral Fellowship.
We thank Griffith colleagues Dr. Myllena Melo for
contributing to the T. b. brucei and HEK-293 assays and Ms
Shi Shi Zhang for assistance with the culturing of P. falciparum.
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1,4,5,16-tetrahydroxytetraphenylene. Tetrahedron 2004, 60, 3523−
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17) Yang, M.; Li, J.; Li, A. Total synthesis of clostrubin. Nat.
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(
Synthesis and hypoglycemic activity evaluation of rhein amide
derivatives. Med. Chem. Res. 2013, 22, 2228−2234.
(19) Davies, J. S.; Higginbotham, C. L.; Tremeer, E. J.; Brown, C.;
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D
Org. Lett. XXXX, XXX, XXX−XXX