Synthesis and biological evaluation of ABCD ring fragments of the kibdelones

Article abstract of DOI:10.1002/anie.201007613

Arylation goes platinum: The synthesis of the ABCD ring fragments of the kibdelones has been achieved through a novel Pt^IV-catalyzed arylation of a quinone monoketal followed by photocyclization (see scheme). Biological evaluation in the NCI 60-cell screen revealed that the kibdelone ABCD ring analogues were about 2000 times less active than kibdelones B and C, suggesting that the tetrahydroxanthone structure of the kibdelones is crucial for cytotoxicity. Copyright

Full text of DOI:10.1002/anie.201007613

DOI: 10.1002/anie.201007613
Natural Product Synthesis
Synthesis and Biological Evaluation of ABCD Ring Fragments of the
Kibdelones**
David L. Sloman, Branko Mitasev, Stephen S. Scully, John A. Beutler, and John A. Porco Jr.*
The kibdelones A–C (1–3) and their isomeric metabolites (cf.
isokibdelone C; 4) are hexacyclic tetrahydroxanthone natural
products recently isolated by Capon and co-workers from the
rare Australian actinomycete Kibdelosporangium sp.
(Figure 1).[1] An interesting property is the facile equilibration
of kibdelones B (2) and C (3) to a mixture of 1–3 through
keto–enol tautomerizations followed by quinone–hydroqui-
none redox reactions.[1] Related natural products include
simaomicin a (5) which has been shown to sensitize cancer
cells to cytotoxic agents including bleomycin at nanomolar
concentrations and to exhibit potent antimalarial and anti-
coccidial activities.[2] Evaluation of the kibdelones in the NCI
60-cell panel of human cancer cell lines revealed that they are
active at low nanomolar concentrations against a number of
human tumor cell lines. For example, kibdelone A has a GI50
of 1.2 nm against a SR (leukemia) tumor cell line and < 1 nm
(GI50) against SN12C (renal) cell carcinoma.[1] In addition, the
kibdelones were shown to display novel COMPARE analysis
profiles for cancer cell growth inhibition.
There has been substantial work towards the synthesis of
the polycyclic xanthones including cervinomycin A2 (6), but
more limited studies on the synthesis of the corresponding
tetrahydroxanthones.[3] Our initial strategy to construct the
ABCD ring fragment 7 involved Diels–Alder cycloaddition of
heterocyclic quinone 8 and hydroxystyrene 9 (Scheme 1).
Figure 1. Representative polycyclic xanthone natural products.
Scheme 1. Proposed cycloaddition of heterocyclic quinone 8 and
styrene 9.
[*] D. L. Sloman, B. Mitasev, S. S. Scully, Prof. J. A. Porco Jr.
Department of Chemistry, Center for Chemical Methodology and
Library Development (CMLD-BU), Boston University
590 Commonwealth Avenue, Boston, MA 02215 (USA)
Fax: (+1)617-358-2847
Literature reports have described [4+2] cycloadditions of
styrenes and quinones including applications in natural
product synthesis.[4] We envisioned that the cycloaddition
may proceed through the hydrogen-bonded assembly A (exo
cycloaddition geometry shown). There are literature prece-
dents in which intermolecular hydrogen-bonding has been
utilized to accelerate and control the stereochemistry of
Diels–Alder cycloadditions.[5] Here, we report our efforts
directed towards this approach which ultimately led to the
serendipitous discovery of a novel PtIV-catalyzed arylation to
assemble the ABCD ring fragment of the kibdelones.
E-mail: porco@bu.edu
Dr. J. A. Beutler
Molecular Targets Laboratory, NCI
Frederick, MD 21702 (USA)
[**] Financial support from the National Institutes of Health (R01
CA137270) and Merck Research Laboratories is gratefully acknowl-
edged. We thank Andrew Little and Dr. Stꢀphane Roche for
extremely helpful and stimulating discussions, and Drs. Richard Ball
and Jeff Bacon for X-ray crystallographic data.
The synthesis of the requisite isoquinolinone 8 began with
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201007613.
condensation of homophthalic acid 10[6] with butanoic
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Initial attempts at fragment coupling of 9 and 16 using
established ionic Diels–Alder conditions (e.g. TMSOTf in
CH3CN) did not lead to observable cycloaddition products.
However, under these conditions arylation product 17 was
unexpectedly isolated in 15% yield. A report by Sartori and
co-workers described the use of stoichiometric amounts of
Et2AlCl to afford biaryls from quinone monoketals and
phenols.[13] Unfortunately, latter conditions did not effect
conversion of 9 and 16 to biaryl product 17. Since the desired
B–D ring connection was established through this unexpected
coupling, we conducted an extensive screen of both Brønsted
and Lewis acids to improve the yield of the transformation.[6]
Following evaluation of reaction conditions, we identified
PtIV, AuIII, and InIII catalysts for the arylation (Table 1). AuCl3
Scheme 2. Reagents and conditions: a) 2:1 pyridine:butyric anhydride
reflux; b) 2.0m MeNH2 THF, RT, CSA, toluene, 858C; c) BBr3, THF,
À788C–RT; d) Ag2O, CHCl3; e) AlCl3, pyridine, CH2Cl2; f) Li2CO3, MeI,
DMF 458C; g) TBDPS-Cl, DMAP, TEA, CH2Cl2; h) MCPBA, CH2Cl2,
NaHCO3, MeOH 08C; i) vinyl tributyltin, [Pd(PPh3)4], toluene 858C;
THF=tetrahydrofuran, CSA=camphor sulfonic acid, DMAP=4-dime-
thylaminopyridine, MCPBA=m-chloroperoxybenzoic acid.
Table 1: Evaluation of conditions for PtIV arylation.[a]
anhydride and pyridine (Scheme 2). Treatment of the result-
ing isocoumarin with methylamine in THF and dehydration
afforded isoquinolinone 11.[7] Demethylation of 11 with BBr3
followed by oxidation with Ag2O afforded the heterocyclic
quinone 12. To access hydroxystyrene 9, commercially
available bromovanillin 13 was demethylated with AlCl3 in
pyridine and selectively methylated with Li2CO3 and MeI in
DMF[8] which was followed by silyl protection to afford
aldehyde 14 (55% yield, 3 steps). Dakin oxidation of 14 with
m-CPBA,[9] followed by hydrolysis of the intermediate
formate, provided a phenol intermediate which was directly
subjected to Stille coupling with vinyl tributylstannane to
afford hydroxystyrene 9 (63%, 3 steps).[10]
Entry
Catalyst (mol%)
t [h]
Yield [%][a]
1
2
3
4
5
6
AuCl3 (10)
InCl3 (10)
6
12
6
6
6
25
27
23
25
33
55
H2PtCl6·6H2O (5)
H2PtBr6·9H2O (5)
[*]
PtCl4 (5)
PtBr4[*] (5)
4
[a] All reactions run in CH3CN at 658C; [*] with 10 mol% water. [b] Yield
of isolated products.
Unfortunately, attempted thermal and catalyzed Diels–
Alder cycloaddition of quinone 12 and hydroxystyrene 9 were
unsuccessful, largely due to instability and decomposition of
the quinone 12. To improve the stability and handling of the
AB quinone reaction partner, we targeted preparation of the
corresponding quinone monoketal 16 (Scheme 3). Moreover,
and InCl3 provided modest yields (20–25%) of the biaryl
product
(entries 1
and
2).
Chloroplatinic
acid
(H2PtCl6·6H2O), bromoplatinic acid (H2PtBr6·9H2O), and
PtCl4 (entries 3–5) provided moderate yields of arylation
product 17 (25–35%). Ultimately, PtBr4 was found to be
optimal providing 2-vinylbiphenyl 17 in yields up to 55% on a
multigram scale (Table 1). Interestingly, we also isolated by-
product 18, a dimer of the quinone monoketal, from arylation
reactions in 4–6% yield and as the sole product when SnCl4
was employed as a Lewis acid.[6] The structure of dimer 18 was
determined by single-crystal X-ray structure analysis
(Figure 2).[14]
Additional evaluation of the PtBr4 arylation conditions
revealed that the presence of water was necessary for catalytic
activity.[15] Kobayashi and co-workers have also reported aza-
Michael additions of carbamates to enones catalyzed by the
platinum–aqua complex PtCl4·5H2O.[16] A survey of water
stoichiometry using PtBr4 as catalyst and freshly distilled
acetonitrile revealed the optimal catalyst:water ratio to be
2:1.[6] A literature report of PtIV carbohydrate complexes
indicates that the pKa of water molecules complexed with
platinum metal centers can decrease by as much as 13 orders
of magnitude.[17b] In addition, a crystal structure of a cis-
diaqua–PtIV complex with [18]crown-6 shows that the PtIV-
bound water molecules may hydrogen-bond to ether oxy-
gens.[17c]
Scheme 3. Reagents and conditions: a) BCl3, THF, À788C–RT;
b) PIDA, MeOH, 08C–RT; c) NCS, PPh3, DMA. PIDA=iodobenzene
diacetate, NCS=N-chlorosuccinimide, DMA=dimethylformamide.
we reasoned that 16 may be a candidate for ionic Diels–Alder
cycloaddition with styrene 9 under Lewis-acidic conditions.[11]
Selective demethylation of isoquinolinone 11 with BCl3,
followed by oxidation with iodosobenzene diacetate (PIDA)
in methanol, provided quinone monoketal 15 in 90% yield (2
steps). Compound 15 proved to be a suitable substrate for
chlorination with catalytic triphenylphosphine (PPh3) and N-
chlorosuccinimide[12] enabling access to quinone monoketal
16 in 72% yield.
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Figure 4. X-ray crystal structure of 19. Cl green, O red, N blue, C gray,
H white.
ature or above. The increased reactivity at elevated temper-
ature may arise from overcoming the rotational barrier of
biaryl 17.[21]
To elaborate protected dihydrophenanthrene 21 to a B-
ring quinone, we first attempted selective demethylation
using standard conditions (e.g. BBr3, BCl3, TMSI, and AlCl3)
(Scheme 4). Unfortunately, these conditions were found to be
Figure 2. X-ray structure of biaryl dimer 18. Cl green, O red, N blue, C
gray, H white.
Based on the water requirement for the reaction, we
envision two possible activated quinone monoketal inter-
mediates as shown in Figure 3. In the first case (B), hydrogen
bond activation of the ketal may be followed by SN2’ addition
Scheme 4. Reagents and conditions: a) hn (Pyrex filter), cyclohexane;
b) TBAF, THF 08C. TBAF=tetrabutylammonium fluoride.
Figure 3. Possible active intermediates for PtIV-mediated arylation.
to the activated acetal.[18] In the second case (C), dual p-
activation of the quinone monoketal by platinum and s-
activation of the quinone monoketal by hydrogen bonding
from the platinum–aqua complex may lead to arylation.[19,20]
Alternatively, PtIV–aqua complexes may dissociate a water
molecule and activate the ketal by direct coordination to
PtIV.[17a] We believe the regioselectivity of the arylation is
influenced by steric bulk of the TBDPS protecting group as
formation of the undesired regioisomer was not observed.
With 2-vinylbiphenyl 17 in hand, we achieved the syn-
thesis of the ABCD ring fragment through photoelectrocyc-
lization[21] in cyclohexane. Silyl deprotection of the photo-
cyclization product afforded 19 in 61% yield (two steps;
Scheme 3). The structure of dihydrophenanthrene 19 was
confirmed by single-crystal X-ray structure analysis[14]
(Figure 4). We also isolated the corresponding phenanthrene
20 from a gram scale photocyclization in an immersion well in
5% yield. Attempts to conduct the photocyclization of 17 in
the presence of oxygen have thus far failed to produce 20 in
higher yield. Analysis of molecular models of 17 revealed that
the low-energy biaryl conformers are bisected.[6] Optimiza-
tion of the photocyclization conditions showed higher con-
versions when the reaction was conducted at room temper-
unselective, with mixtures of both B and C ring demethylated
products observed. Fortunately, compound 21 could be
selectively acylated in aprotic solvents due to the strongly
hydrogen bonded B-ring phenol. Oxidative cleavage with
CAN in acetonitrile/pH 7.0 buffer followed by desilylation
afforded the tetracyclic quinone 22 (Scheme 5). Oxidation of
the B vs. D ring was confirmed by HMBC experiments.[6]
Further experiments revealed that 23 was sensitive to basic
deacylation conditions. Fortunately, treatment of 23 with
Oteraꢀs distannoxane catalyst[22] in toluene/methanol
afforded tetracycle 23, a compound bearing the ABCD core
of kibdelone B in 85% yield. In the presence of aqueous
sodium dithionite, the B-ring of 23 was cleanly reduced to
afford hydroquinone 24 in 90% yield, a compound analogous
to the ABCD ring structure of kibdelone C (3).
Compounds 19, 20, 23, and 24 were evaluated in the NCI
60-cell screen.[23] Compounds 19 and 20 were judged to be
inactive, with mean cell growth of 82% and 93% of control,
respectively, at 10 mm. Compounds 23 and 24 passed the
criteria for testing in dose-response format, with mean cell
growths of 63% and 54%, respectively. In dose-response
format, both 23 and 24 bearing the ABCD functionalities of
kibdelones B and C, respectively, showed mean GI50 values of
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[3] Cervinomycin A2: a) S. Omura, A. Nakagawa, K. Kushida, H.
Shimizu, G. J. Lukacs, Antibiotica 1987, 40, 301 – 308; b) H.
Tanka, K. Kawakita, H. Suzuki, P. S. Nakagawa, S. J. Omura, J.
Antibiot. 1989, 42, 431 – 439; c) G. Mehta, Y. Venkateswarlu, J.
Chem. Soc. Chem. Commun. 1988, 1200 – 1202; d) T. R. Kelly,
C. T. Jagoe, Q. Li, J. Am. Chem. Soc. 1989, 111, 4522 – 4524;
e) A. V. Rao, J. S. Yadav, K. Reddy, V. Upender, Tetrahedron
Lett. 1991, 32, 5199 – 5202; f) J. S. Yadav, Pure Appl. Chem. 1993,
65, 1349 – 1356; g) G. Mehta, S. R. Shah, Y. Venkateswarlu,
Tetrahedron 1994, 50, 11729 – 11742; lysolipin: h) R. O.
Duthaler, U. H. Wegmann, Helv. Chim. Acta 1984, 67, 11755 –
11766; i) Sch 56036: E. R. Walker, S. Y. Leung, A. G. M. Barrett,
Tetrahedron Lett. 2005, 46, 6537 – 6540.
[4] a) W. B. Manning, T. P. Kelly, G. M. Muschik, J. Org. Chem.
1980, 45, 2535 – 2536; b) G. M. Muschik, T. P. Kelly, W. B.
Manning, J. Org. Chem. 1982, 47, 4709 – 4712; c) M. J. Tanga,
E. J. Reist, J. Heterocycl. Chem. 1991, 28 – 29; d) N. D. Willmore,
D. A. Hoic, T. J. Katz, J. Org. Chem. 1994, 59, 1889 – 1891;
e) M. C. Carreꢁo, J. Mahugo, A. Urbano, Tetrahedron Lett. 1997,
38, 3047 – 3050; f) T. J. Katz, L. Liu, N. D. Willmore, J. M. Fox,
A. L. Rheingold, S. Shi, C. Nuckolls, B. H. Rickman, J. Am.
Chem. Soc. 1997, 119, 10054 – 10063; g) K. Krohn, U. Loock, K.
Paavilainen, B. M. Hausen, W. H. Schmalle, H. Kiesele, ARKI-
VOC 2001, 2, 88 – 130.
[5] a) M. J. Fisher, W. J. Hehre, S. D. Kahn, L. E. Overman, J. Am.
Chem. Soc. 1988, 110, 4625 – 4633; b) R. Tripathy, P. J. Carroll,
E. R. Thornton, J. Am. Chem. Soc. 1990, 112, 6743 – 6744;
c) K. L. Sorgi, J. J. McNally, G. C. Leo, J. Org. Chem. 1994, 59,
5088 – 5089; d) J. C. C. Atherton, S. Jones, Tetrahedron Lett.
2001, 42, 8239 – 8241; e) Y. Huang, V. H. Rawal, J. Am. Chem.
Soc. 2002, 124, 9662 – 9663; f) L. R. Domingo, M. J. Aurell, M.
Arno, J. A. Saez, J. Org. Chem. 2007, 72, 4220 – 4227.
[6] See the Supporting Information for complete experimental
details.
Scheme 5. Reagents and conditions: a) acetyl chloride, DIEA, CH2Cl2,
08C; b) CAN, CH3CN/pH 7 buffer, 08C; c) HF-pyridine, THF, 08C;
d) Otera’s catalyst, 2:1 toluene:MeOH, 708C; e) Na2S2O4, H2O:EtOAc.
DIEA=diisopropylethylamine, THF=tetrahydrofuran, CAN=ceric am-
monium nitrate.
4.5 mm while having no selectivity. In comparison, kibdelo-
ne C (3), the most potent of the natural products in the
kibdelone series, had a mean GI50 of 2.4 nm, with 100-fold
selectivity between the most and least sensitive cell lines
tested. Thus, it is apparent that the contribution of the E and F
rings of the kibdelone structure is highly important for
cytotoxic activity.
In summary, a proposed Diels–Alder cycloaddition to
construct the ABCD ring structure of the kibdelones led to
the discovery of a novel PtIV-mediated arylation of quinone
monoketals to produce a complex 2-vinylbiphenyl adduct.
Photocycloaddition and further oxidation of this compound
was used to access ABCD analogues of the kibdelones.
Analogues were evaluated for initial biological activity in the
NCI 60-cell screen and were found to be about 2000 times less
active in comparison to kibdelones B and C, suggesting that
the tetrahydroxanthone structure of the kibdelones may be
crucial for cytotoxicity. Studies towards the completion of the
total synthesis of the kibdelones, as well as mechanistic
studies and substrate scope of the PtIV arylation of quinone
monoketals, is ongoing and will be reported in due course.
[7] H. Ahmed, N. Rama, M. Malana, G. Qadeer, Indian J. Chem.
Sect. B 2006, 45, 820 – 822.
[8] a) W. E. Wymann, R. Davis, J. W. Patterson, J. R. Pfister, Synth.
Commun. 1988, 18, 1379 – 1384; b) M. N. Masuno, I. N. Pessah,
M. M. Olmstead, T. F. Molinski, J. Med. Chem. 2006, 49, 4497 –
4511.
[9] D. A. Lanfranchi, G. Hanquet, J. Org. Chem. 2006, 71, 4854 –
4861.
[10] M.-C. Matos, P. V. Murphy, J. Org. Chem. 2007, 72, 1803 – 1806.
[11] a) P. G. Gassman, D. A. Singleton, J. J. Wilwerding, S. P. Chavan,
J. Am. Chem. Soc. 1987, 109, 2182 – 2184; b) K. Schildknegt, J.
Aube, Chemtracts Org. Chem. 1996, 9, 237 – 241; c) R. Sanghi,
P. S. Vankar, Y. D. Vankar, J.Indian Chem. Soc. 1998, 75, 709 –
715; d) B. Witulski, C. Alayrac, Sci. Synth. 2007, 25, 405 – 422.
[12] A. Sakakura, A. Ukai, K. Ishihara, Nature 2007, 445, 900 – 903.
[13] For arylation of quinone monoketals with phenols, see: a) G.
Sartori, R. Maggi, F. Bigi, M. Grandi, J. Org. Chem. 1993, 58,
7271 – 7273; b) G. Sartori, R. Maggi, F. Bigi, S. Giacomelli, C.
Porta, A. Arienti, G. Bocelli, J. Chem. Soc. Perkin Trans. 1 1995,
2177 – 2181.
Received: December 4, 2010
Published online: February 18, 2011
Keywords: antitumor agents · kibdelone · natural products ·
.
photochemistry · platinum
[14] CCDC 793693 (18) and 793694 (19) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif. See the Sup-
porting Information for complete experimental details.
[15] For examples of water as an additive in organic transformations,
see: a) S. Ribe, P. Wipf, Chem. Commun. 2001, 299 – 307; b) H.
Yamamoto, K. Futatsugi, Angew. Chem. 2005, 117, 1958 – 1977;
Angew. Chem. Int. Ed. 2005, 44, 1924 – 1942.
[16] S. Kobayashi, K. Kakumoto, M. Sugiura, Org. Lett. 2002, 4,
1319 – 1322.
[17] a) H. Junicke, C. Bruhn, D. Strohl, R. Kluge, D. Steinborn, Inorg.
Chem. 1998, 37, 4603 – 4606; b) H. Junicke, C. Bruhn, R. Kluge,
[1] a) R. Ratnayake, E. Lacey, S. Tennant, J. H. Gill, R. J. Capon,
Org. Lett. 2006, 8, 5267 – 5270; b) R. Ratnayake, E. Lacey, S.
Tennant, J. H. Gill, R. J. Capon, Chem. Eur. J. 2007, 13, 1610 –
1619; c) R. J. Capon, E. Lacey, R. Ratnayake, J. H. Gill, S.
Tennant, PCT Int. Appl. WO 2007095696, 2007.
[2] a) T. M. Lee, G. T. Carter, D. B. Borders, J. Chem. Soc. Chem.
Commun. 1989, 1771 – 1772; b) G. T. Carter, J. J. Goodman, M. J.
Torrey, D. B. Borders, S. J. Gould, J. Org. Chem. 1989, 54, 4321 –
4323; c) W. M. Maiese, J. Korshalla, J. Goodman, M. J. Torrey, S.
Kantor, D. P. Labeda, M. Greenstein, J. Antibiot. 1990, 43, 1059 –
1063; d) M. Arai, H. Sato, H. Kobayashi, M. Suganuma, T.
Kawabe, H. Tomoda, S. Omura, Biochem. Biophys. Res.
Commun. 2004, 317, 817 – 822.
2514
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 2511 –2515

A. S. Serianni, D. J. Steinborn, J. Am. Chem. Soc. 1999, 121,
6232 – 6241; c) C. Wagner, C. Bruhn, O. Gravenhorst, D. J.
Steinborn, Z. Kristallogr. 2000, 215, 61 – 64.
3822 – 3825; d) Y. Yamamoto, J. Org. Chem. 2007, 72, 7817 –
7831.
[20] For PtIV–alkene complexes, see: E. J. Parsons, R. D. Larsen, P. W.
Jennings, J. Am. Chem. Soc. 1985, 107, 1793 – 1794.
[18] For SN2’ addition to allylic acetals, see: a) A. Ghribi, A. Alexakis,
J. F. Normant, Tetrahedron Lett. 1991, 32, 5199 – 5202; b) E.
Gomez-Bengoa, N. M. Heron, M. T. Didiuk, C. A. Luchaco,
A. H. Hoveyda, J. Am. Chem. Soc. 1998, 120, 7649 – 7650; for a
review on carbophilic p activation of platinum see: c) A.
Fꢂrstner, P. W. Davies, Angew. Chem. 2007, 119, 3478 – 3519;
Angew. Chem. Int. Ed. 2007, 46, 3410 – 3449.
[19] For dual activation by oxophilic/carbophilic catalysts see: a) N.
Asao, T. Kasahara, Y. Yamamoto, Tetrahedron Lett. 2001, 42,
7903 – 7905; b) S. Kamijo, Y. Yamamoto, J. Org. Chem. 2003, 68,
4764 – 4771; c) R. Yanada, S. Obika, H. Kono, Y. Takemoto,
Angew. Chem. 2006, 118, 3906; Angew. Chem. Int. Ed. 2006, 45,
[21] For photocyclizations of 2-vinylbiphenyls, see: a) S. W. Horgan,
D. D. Morgan, M. Orchin, J. Org. Chem. 1973, 38, 3801 – 3803;
b) R. Koussini, R. Lapouyade, P. Fornier de Violet, J. Am. Chem.
Soc. 1978, 100, 6679 – 6683; c) P. Fornier de Violet, R. Bonneau,
R. Lapouyade, R. Koussini, W. R. Ware, J. Am. Chem. Soc. 1978,
100, 6683 – 6687; d) F. D. Lewis, X. Zuo, Photochem. Photobiol.
Sci. 2003, 2, 1059 – 1066.
[22] J. Li, X. Chen, A. W. G. Burgett, P. Harran, Angew. Chem. 2001,
113, 2754 – 2757; Angew. Chem. Int. Ed. 2001, 40, 2682 – 2685.
[23] a) M. R. Boyd, K. D. Paull, Drug Dev. Res. 1995, 34, 91 – 109;
b) R. H. Shoemaker, Nat. Rev. Cancer 2006, 6, 813 – 823.
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