Formal total synthesis of platencin

Full text of DOI:10.1002/anie.200900447

Angewandte
Chemie
DOI: 10.1002/anie.200900447
Natural Products Synthesis
Formal Total Synthesis of Platencin**
Georgy N. Varseev and Martin E. Maier*
The increasing appearance of bacterial resistance has stimu-
lated a resumption of the search for novel antibiotics. Not
only various depsipeptides but also structurally novel poly-
cyclic polyketide and terpene derivatives with antibiotic
activity have been discovered.[1,2] The two closely related
antibiotics platencin[3] and platensimycin[4] were described by
a research group from Merck. Platencin (1), the most recently
Scheme 1. Possible late-stage interconversion of the platensimycin
core into the platencin system.
2006, 10 total or formal total syntheses have been
reported.[9,10] The year 2008 saw the publication of seven
platencin syntheses.[11] We also became interested in the
synthesis of platencin and conceived a unique route to the
advanced intermediate 3 (Scheme 2). Our approach was
inspired by the bicyclo[3.2.1]octane–bicyclo[2.2.2]octane
interconversion that is evident from the two natural products.
Two prominent methods are known for such transformations:
A pinacol rearrangement of bicyclo[2.2.2]octane systems,
which can be formed through a Diels–Alder reaction, offers
an entry to [3.2.1] systems;[12,13] on the other hand, the
homoallyl–homoallyl radical rearrangement, which might
proceed through a cyclopropylcarbinyl radical, was used by
the research group of Ihara to convert a [3.2.1] system into a
[2.2.2] system.[14,15] In fact, this skeleton-interconversion
strategy was also used by Nicolaou and co-workers[11a] and
Lee and co-workers[11c] in their syntheses of platencin. We
conceived a related strategy independently (Scheme 2) but
encountered problems with the rearrangement of D into C.[16]
According to this synthetic plan, compound E might be
synthesized by conjugate addition to a bicyclic enone F, which
could be prepared by the method of Toyota and co-work-
ers[14,17] by the palladium-catalyzed oxidative cyclization of an
allylcyclohexenone G. This substrate, in turn, could be
constructed by the alkylation and reduction of a 3-alkoxy
cyclohex-2-en-1-one.
discovered of the two, was isolated from a strain of
Streptomyces platensis, MA7339. Like platensimycin (2; the
aryl group Ar is the same as that in 1), platencin (1) shows
potent antimicrobial activity against a broad spectrum of
Gram-positive bacteria. In particular, it inhibits key anti-
biotic-resistant pathogens, such as methicillin-resistant Staph-
ylococus aureus, vancomycin-resistant Enterococci, and Strep-
tococcus pneumoniae.
The screening assay was targeted against bacterial fatty-
acid biosynthesis; thus, both 1 and 2 inhibit this process.[5] In
contrast to 2, platencin (1) blocks two condensing enzymes,
namely, b-ketoacyl synthase (KAS) II and III. Both com-
pounds contain a highly substituted 3-amino-2,4-dihydroxy-
benzoic acid moiety and a rather hydrophobic polycyclic
enone–acid unit. Biosynthetic studies revealed that the
terpene moiety in both cases originates from the non-
mevalonate MEP pathway[6,7] (MEP = methylerythritol phos-
phate) and is formed via the diterpene copalyl pyrophosphate
(see the Supporting Information).[8] Alternatively, a late-stage
interconversion of the two ring systems could be possible, as
shown by the carbenium-ion structures
A
and
B
(Scheme 1).[3b]
Initially, we performed some model studies on the
palladium(II)-catalyzed cycloalkenylation of silyl enol ether
7 (Scheme 3). The original plan was to convert the desired
The potent in vivo activities and novel intriguing struc-
tures of these compounds prompted a number of attempts at
their synthesis. Since platensimycin was first described in
[*] Dipl.-Chem. G. N. Varseev, Prof. Dr. M. E. Maier
Institut fꢀr Organische Chemie, Universitꢁt Tꢀbingen
Auf der Morgenstelle 18, 72076 Tꢀbingen (Germany)
Fax: (+49)7071-295-137
E-mail: martin.e.maier@uni-tuebingen.de
Homepage: http://www.uni-tuebingen.de/uni/com/welcome.htm
[**] Financial support by the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie is gratefully acknowledged. We
thank Graeme Nicholson for HRMS measurements and analytical
GC on a chiral phase.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200900447.
Scheme 2. Synthetic plan for the platencin core structure 3.
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Table 1: Optimization of the palladium-catalyzed alkene–silyl enol ether
cyclization.[a]
Entry
R3Si
T
Conc.
Pd [mol%]
Ratio 8/9/6[b]
1
2
3
4
5
6
TMS
TMS
TIPS
TBS
TBS
TBS
RT
0.05m
0.2m
0.3m
0.1m
0.1m
0.05m
10
10
1
10
10
5[c]
40:50:trace
33:17:50
38:trace:60
80:20:trace
80:20:3
458C
458C
RT
458C
458C
>95:trace:trace
[a] Reactions were carried out with 0.5 mmol of the substrate 7 in DMSO
under oxygen (1 atm) for 24–48 h. [b] The product ratio was determined
1
by H NMR spectroscopy. [c] The catalyst was added slowly (over 4 h).
TBS=tert-butyldimethylsilyl, TIPS=triisopropylsilyl, TMS=trimethyl-
silyl.
ester 4[19] (Scheme 4). Thus, the formylation of 4 with isobutyl
formate, followed by the addition of allyl chloroformate, gave
an E/Z mixture of enol carbonates 13, which underwent
isomerization upon flash chromatography to form mostly the
Z isomer, the structure of which was assigned by NMR
spectroscopy, in 89% yield. This enol carbonate underwent a
rapid decarboxylative allylation[22,23] under Pd(OAc)2/PPh3
catalysis with the formation of a quaternary center to give
the 2-oxocyclohex-3-ene carbaldehyde 14 in high yield. In the
next step, the enone as well as the aldehyde functionality were
reduced with NaBH4 and CeCl3 in MeOH to give cyclo-
hexenone 15. Surprisingly, the vinylogous ester functionality
was also reduced under these conditions; the use of expensive
reducing agents, such as DIBAL-H, was thus avoided. The
crude hydroxyketone 15 was then subjected to pivaloylation
to afford pivalate 16 in 94% yield from aldehyde 14. Enone 16
was converted into silyl enol ether 17, which underwent
cyclization under our optimized conditions to give the 7-
Scheme 3. Synthesis and oxidative palladium-catalyzed transformation
of silyl enol ether 7: a) LDA (1.1 equiv), THF, ꢀ808C, 1 h, then allyl
bromide (1.3 equiv), ꢀ808C!RT, 12 h, 90%; b) LDA (1.1 equiv), THF,
ꢀ808C, 1 h, then methyl vinyl ketone (1 equiv), ꢀ808C, 0.5 h, 84%;
c) (CH2OH)2 (20 equiv), PPTS (0.4 equiv), benzene, reflux, 2–12 h;
d) DIBAL-H (1.5 equiv), THF, ꢀ80!ꢀ608C, 1 h; e) p-TsOH·H2O
(0.04 equiv), Et2O/H2O (100:1), 208C, 0.5 h, 80% from 5; f) LDA
(1.5 equiv), THF, ꢀ808C, 1 h, then R3SiCl (2 equiv), HMPA (1.5 equiv),
room temperature, 1.5 h, approximately 90%; g) Pd(OAc)2 (cat.),
DMSO, O2, 85% (see Table 1); h) p-TsOH·H2O (1 equiv), acetone,
208C, 40 min; i) KOtBu, THF, tBuOH (2:1), ꢀ808C, 2.5 h, 88% from
8; ketoenone 10 was used without purification. R3Si=Me3Si, iPr3Si, or
tBuMe2Si; DIBAL-H=diisobutylaluminum hydride, DMSO=dimethyl
sulfoxide, HMPA=hexamethylphosphoramide, LDA=lithium diisopro-
pylamide, PPTS=pyridinium p-toluenesulfonate, Ts=p-toluenesul-
fonyl.
bicyclic product into the decalin derivative 11 and then to
perform the key skeletal rearrangement on a tricyclic system
derived from 11. However, with our model system 6, which
was prepared by the Stork alkylation strategy[18] from 3-
isobutoxycyclohex-2-en-1-one[19] (4) under the conditions
reported by Toyota et al.,[17] the cyclization resulted in the
formation of a mixture of three products (Scheme 3, Table 1).
A change in the trialkylsilyl group of the silyl enol ether 7
from Me3Si to tBuMe2Si led to a decrease in the amount of the
desilylated cyclohexenone 6 formed but not to a decrease in
the formation of cyclohexadienone 9, which results from
oxidative desilylation.[20] Finally, a solution to this problem
was found in the slow addition of the catalyst to the reaction
mixture (Table 1, entry 6). Thus, the addition of the catalyst
solution over 4 h to a 0.05m solution of silyl enol ether 7 (R =
tBuMe2Si) in DMSO resulted in the clean formation of the
desired product 8 in 85% yield. Enone 8 was then converted
into the tricyclic diketone 11 in two steps (Scheme 3).
Unfortunately, the radical rearrangement of tricyclic deriva-
tives of 11 did not give the desired products.[21]
methylenebicyclo[3.2.1]oct-3-en-2-one 18. A subsequent
Scheme 4. Synthesis of the bicyclic ketoester 20: a) NaH, HCO2iBu,
24 h, 08C, then ClCO2allyl, KH (cat.), THF, 08C, 1 h; b) Pd(OAc)2
(1.3 mol%), PPh3, THF, 208C, 1 h, 92% from 4; c) NaBH4,
CeCl3·7H2O, MeOH, 08C, 0.5 h, then p-TsOH, H2O/Et2O, room temper-
ature, 0.5 h; d) PivCl (2 equiv), pyridine (4 equiv), DMAP (0.05 equiv),
CH2Cl2, room temperature, 48 h, 94% from 14; e) LDA (1.5 equiv),
TBSCl (2 equiv), HMPA (1 equiv), THF, ꢀ808C!RT, overnight, 88%;
After the optimization of this cycloalkenylation reaction
we focused on the synthesis of
a functionalized 7-
methylenebicyclo[3.2.1]octan-2-one, such as 18. This
approach would enable the formation of the cyclohexenone
ring of platencin after the rearrangement of the bicyclic
substructure. The racemic synthesis began with the vinylogous
=
f) O2, Pd(OAc)2 (0.058 equiv), DMSO, 85%; g) H2C C(OMe)OTBS
(19; 1.5 equiv), TiCl4 (1.2 equiv), CH2Cl2, ꢀ808C, 12 h, 88%.
DMAP=4-dimethylaminopyridine.
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Mukaiyama-type Michael addition[24] of the silyl ketene
acetal[25] 19 to enone 18 in the presence of TiCl4 (1.2 equiv)
gave only the desired diastereomer 20. Thus, the nucleophile
attacks the enone syn to the one-carbon-atom methylene
bridge.
In preparation for the intended skeletal rearrangement,
the keto functionality of 20 was reduced under various
conditions (Scheme 5). The use of sodium borohydride, zinc
borohydride, or Meerwein–Ponndorf–Verley conditions (alu-
minum isopropoxide/2-propanol) always gave a mixture of
alcohols, at best in a 3:1 ratio. Finally, we discovered that the
reaction of 20 with Et3SiH and TiCl4 proceeded with exclusive
formation of the alcohol diastereomer 21. The configuration
of the OH-bearing stereocenter could be determined from
NOESY experiments. Alcohol 21 was then converted into
xanthate 22. However, the radical rearrangement of xanthate
ester 22 did not proceed under the conditions reported for the
first total synthesis of platencin by Nicolaou et al. (AIBN,
Bu3SnH, toluene, 1008C).[11a,26] With a methoxymethyl or
acetyl protecting group instead of the pivaloate group, this
reaction gave the desired rearrangement product, but in very
poor yield together with large amounts of by-products.[21]
Better results were obtained when the reaction was carried
out under conditions reported by Park et al., namely, with a
combination of tetrabutylammonium peroxydisulfate and
sodium formate.[27] An 82:18 mixture of the rearranged
product 23 and the simple deoxygenation product 24 was
obtained in 38% yield under these conditions in DMSO. In
DMF, the reaction afforded the same product mixture in 25%
yield.
Scheme 6. Efficient conversion of ketoester 20 into the bicyclo-
[2.2.2]octane system 23, and the transformation of 23 into the core
structure 3 of platencin: a) TsNHNH2 (1.3 equiv), MeOH, 608C, 5 h,
95%; b) NaCNBH3, ZnCl2, MeOH, 608C, 3 h, 60%; the one-pot
preparation of 23 from 20 gave 23 in 54% yield; c) HCl·NH(OMe)Me
(6 equiv), Me3Al (5 equiv), CH2Cl2, 08C, overnight; d) MeLi (6 equiv),
Et2O, ꢀ80!ꢀ308C, overnight; e) LiAlH4 (1 equiv), Et2O, ꢀ80!08C,
2 h, 85% from 23; f) (COCl)2 (5.8 equiv), DMSO (9 equiv), ꢀ808C,
3 h, Et3N, 2 h, 73%; g) NaOH (6.5 equiv), EtOH, 208C, 20 h, 87%.
Compound 25 and the Weinreb amide derived from 23 were used
without purification.
methylmorpholine N-oxide by a previously reported proce-
dure[11a] afforded the desired ketoaldehyde 28 in poor yield
(<25%). On the other hand, Swern oxidation of diol 27 led to
28 in good yield. A final aldol condensation of 28 upon
treatment with NaOH in EtOH gave the advanced inter-
mediate 3 in 87% yield. The overall yield of the platencin
tricyclic core structure 3 from the commercially available
starting material 4 was 17.5% (13 steps).
We also studied an enantioselective approach to 3.
Asymmetry could be introduced by an enantioselective
palladium-catalyzed decarboxylative allylation[23] of the allyl
enol carbonate 13 with a chiral phosphine ligand. According
to the results of Trost and co-workers, the use of the ligand
(S,S)-29 should result in (S)-14 (Scheme 7).[28,29] Indeed, when
this decarboxylative allylation was performed in the presence
of ligand (S,S)-29 at 08C in THF, (+)-14 was formed with
78% ee. When the temperature was lowered to ꢀ208C, (+)-
14 was obtained with an improved ee value of 87%. The use of
optically active 14 should lead to the optically enriched
platencin core structure 3.
In our search for conditions that would provide a better
yield and better selectivity in the key radical rearrangement
to form the bicyclo[2.2.2]octane core, we eventually found
that the desired deoxygenative rearrangement occurred upon
heating a solution of the hydrazone 25 in methanol in the
presence of NaCNBH3 and ZnCl2 to give the
methylenebicyclo[2.2.2]octane
23
in
60%
yield
(Scheme 6).[14b] Although the product 23 was still contami-
nated with 8 mol% of the by-product 24, this impurity could
be removed by flash chromatography of the diol derivative 27.
This diol was obtained in pure form through a very efficient
three-step sequence from 23. Thus, the conversion of ester 23
into the corresponding Weinreb amide, treatment with MeLi
(6 equiv), and reduction of the resulting hemiketal 26 with
LiAlH4 furnished diol 27 in 85% yield from 23. The oxidation
of hemiketal 26 with tetrapropylammonium perruthenate/N-
In summary, we have developed an efficient formal
synthesis of platencin. The tricyclic advanced intermediate 3
was prepared in 13 steps and 17.5% overall yield from the
commercially available starting material 4. Our approach is
based on original key reactions, namely, an asymmetric
decarboxylative allylation of the allyl enol carbonate 13, an
Scheme 5. Rearrangement of xanthate 22: a) Et3SiH (4 equiv), TiCl4
(1.2 equiv), CH2Cl2, ꢀ408C, 15 min, 89%; b) NaH (3 equiv), CS2
(3 equiv), 08C, 0.5 h, MeI (3 equiv), THF, 08C!RT, 1 h, 83%;
c) (Bu4N)2S2O8, HCO2Na, DMSO, 458C, 12 h, 38%, 23/24=82:18.
Scheme 7. Asymmetric approach to platencin (1). dba=dibenzylide-
neacetone.
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[11] a) K. C. Nicolaou, G. S. Tria, D. J. Edmonds, Angew. Chem. 2008,
120, 1804 – 1807; Angew. Chem. Int. Ed. 2008, 47, 1780 – 1783;
b) J. Hayashida, V. H. Rawal, Angew. Chem. 2008, 120, 4445 –
4448; Angew. Chem. Int. Ed. 2008, 47, 4373 – 4376; c) S. Y. Yun,
J.-C. Zheng, D. Lee, Angew. Chem. 2008, 120, 6297 – 6299;
Angew. Chem. Int. Ed. 2008, 47, 6201 – 6203; d) K. Tiefenbacher,
J. Mulzer, Angew. Chem. 2008, 120, 6294 – 6295; Angew. Chem.
Int. Ed. 2008, 47, 6199 – 6200; e) D. C. J. Waalboer, M. C.
Schaapman, F. L. van Delft, F. P. J. T. Rutjes, Angew. Chem.
2008, 120, 6678 – 6680; Angew. Chem. Int. Ed. 2008, 47, 6576 –
6578; f) K. C. Nicolaou, Q.-Y. Toh, D. Y. K. Chen, J. Am. Chem.
Soc. 2008, 130, 11292 – 11293; K. C. Nicolaou, Q.-Y. Toh,
D. Y. K. Chen, J. Am. Chem. Soc. 2008, 130, 14016; g) K. A. B.
Austin, M. G. Banwell, A. C. Willis, Org. Lett. 2008, 10, 4465 –
4468.
[12] See, for example: a) S. A. Monti, S.-C. Chen, Y.-L. Yang, S.-S.
Yuan, O. P. Bourgeois, J. Org. Chem. 1978, 43, 4062 – 4069;
b) D. H. Hua, W. Y. Gung, R. A. Ostrander, F. Takusagawa, J.
Org. Chem. 1987, 52, 2509 – 2517; c) D. Kim, P. J. Shim, J. Lee,
C. W. Park, S. W. Hong, S. Kim, J. Org. Chem. 2000, 65, 4864 –
4870.
[13] For a review about the synthesis of [3.2.1] systems, see: M.-H.
Filippini, J. Rodriguez, Chem. Rev. 1999, 99, 27 – 76.
[14] a) M. Toyota, T. Wada, K. Fukumoto, M. Ihara, J. Am. Chem.
Soc. 1998, 120, 4916 – 4925; b) M. Toyota, T. Asano, M. Ihara,
Org. Lett. 2005, 7, 3929 – 3932.
[15] For reviews, see: a) D. C. Nonhebel, Chem. Soc. Rev. 1993, 22,
347 – 359; b) P. Dowd, W. Zhang, Chem. Rev. 1993, 93, 2091 –
2115.
[16] G. N. Varseev, Tꢂbinger-Gꢁttinger Gesprꢀche zur Chemie von
Mikroorganismen, Zellingen-Retzbach, September 19, 2007.
[17] M. Toyota, T. Wada, Y. Nishikawa, K. Yanai, K. Fukumoto, C.
Kabuto, Tetrahedron 1995, 51, 6927 – 6940.
[18] G. Stork, R. L. Danheiser, J. Org. Chem. 1973, 38, 1775 – 1776.
[19] a) R. Hara, T. Furukawa, H. Kashima, H. Kusama, Y. Horiguchi,
I. Kuwajima, J. Am. Chem. Soc. 1999, 121, 3072 – 3082; b) S.
Yamada, H. Suemune, Chem. Pharm. Bull. 2000, 48, 1171 – 1175.
[20] Y. Ito, T. Hirao, T. Saegusa, J. Org. Chem. 1978, 43, 1011 – 1013.
[21] G. N. Varseev, unpublished results.
[22] a) D. C. Behenna, B. M. Stoltz, J. Am. Chem. Soc. 2004, 126,
15044 – 15045; b) J. T. Mohr, D. C. Behenna, A. M. Harned,
B. M. Stoltz, Angew. Chem. 2005, 117, 7084 – 7087; Angew.
Chem. Int. Ed. 2005, 44, 6924 – 6927; c) S. R. Levine, M. R.
Krout, B. M. Stoltz, Org. Lett. 2009, 11, 289 – 292; d) K. V.
Petrova, J. T. Mohr, B. M. Stoltz, Org. Lett. 2009, 11, 293 – 295.
[23] For a review, see: J. T. Mohr, B. M. Stoltz, Chem. Asian J. 2007, 2,
1476 – 1491.
[24] a) K. Narasaka, K. Soai, Y. Aikawa, T. Mukaiyama, Bull. Chem.
Soc. Jpn. 1976, 49, 779 – 783; b) C. H. Heathcock, M. H. Norman,
D. E. Uehling, J. Am. Chem. Soc. 1985, 107, 2797 – 2799.
[25] a) Y. Kita, J. Segawa, J. Haruta, H. Yasuda, Y. Tamura, J. Chem.
Soc. Perkin Trans. 1 1982, 1099 – 1104; b) C. H. Heathcock, S. K.
Davidsen, K. T. Hug, L. A. Flippin, J. Org. Chem. 1986, 51,
3027 – 3037; c) A. G. Wenzel, E. N. Jacobsen, J. Am. Chem. Soc.
2002, 124, 12964 – 12965.
[26] a) D. H. R. Barton, S. W. McCombie, J. Chem. Soc. Perkin Trans.
1 1975, 1574 – 1585; b) B. M. Trost, N. Cramer, H. Bernsmann, J.
Am. Chem. Soc. 2007, 129, 3086 – 3087.
[27] H. S. Park, H. Y. Lee, Y. H. Kim, Org. Lett. 2005, 7, 3187 – 3190.
[28] For reviews, see: a) B. M. Trost, J. Org. Chem. 2004, 69, 5813 –
5837; b) B. M. Trost, M. R. Machacek, A. Aponick, Acc. Chem.
Res. 2006, 39, 747 – 760; c) B. M. Trost, C. Jiang, Synthesis 2006,
369 – 396.
optimized palladium-catalyzed cycloalkenylation of 7, a
highly diastereoselective Mukaiyama Michael addition of
the silyl ketene acetal 19 to the bicyclic enone 18, and a
radical-mediated reductive rearrangement of the tosylhydra-
zone 25 to construct the bicyclo[2.2.2]octane core of platen-
cin.
Received: January 23, 2009
Published online: April 7, 2009
Keywords: allylation · antibiotics · natural products ·
.
rearrangement · total synthesis
[1] For reviews, see: a) F. von Nussbaum, M. Brands, B. Hinzen, S.
Weigand, D. Hꢀbich, Angew. Chem. 2006, 118, 5194 – 5254;
Angew. Chem. Int. Ed. 2006, 45, 5072 – 5129; b) K. C. Nicolaou,
J. S. Chen, D. J. Edmonds, A. A. Estrada, Angew. Chem. 2009,
121, 670 – 732; Angew. Chem. Int. Ed. 2009, 48, 660 – 719.
[2] B. Bister, D. Bischoff, M. Strꢁbele, J. Riedlinger, A. Reicke, A. T.
Bull, H. Zꢀhner, H.-P. Fiedler, R. D. Sꢂssmuth, Angew. Chem.
2004, 116, 2628 – 2630; Angew. Chem. Int. Ed. 2004, 43, 2574 –
2576.
[3] a) J. Wang, S. Kodali, S. H. Lee, A. Galgoci, R. Painter, K. Dorso,
F. Racine, M. Motyl, L. Hernandez, E. Tinney, S. L. Colletti, K.
Herath, R. Cummings, O. Salazar, I. Gonzalez, A. Basilio, F.
Vicente, O. Genilloud, F. Pelaez, H. Jayasuriya, K. Young, D. F.
Cully, S. B. Singh, Proc. Natl. Acad. Sci. USA 2007, 104, 7612 –
7616; b) H. Jayasuriya, K. B. Herath, C. Zhang, D. L. Zink, A.
Basilio, O. Genilloud, M. T. Diez, F. Vicente, I. Gonzalez, O.
Salazar, F. Pelaez, R. Cummings, S. Ha, J. Wang, S. B. Singh,
Angew. Chem. 2007, 119, 4768 – 4772; Angew. Chem. Int. Ed.
2007, 46, 4684 – 4688.
[4] J. Wang, S. M. Soisson, K. Young, W. Shoop, S. Kodali, A.
Galgoci, R. Painter, G. Parthasarathy, Y. S. Tang, R. Cummings,
S. Ha, K. Dorso, M. Motyl, H. Jayasuriya, J. Ondeyka, K. Herath,
C. Zhang, L. Hernandez, J. Allocco, A. Basilio, J. R. Tormo, O.
Genilloud, F. Vicente, F. Pelaez, L. Colwell, S. H. Lee, B.
Michael, T. Felcetto, C. Gill, L. L. Silver, J. D. Hermes, K.
Bartizal, J. Barrett, D. Schmatz, J. W. Becker, D. Cully, S. B.
Singh, Nature 2006, 441, 358 – 361.
[5] P. Johansson, B. Wiltschi, P. Kumari, B. Kessler, C. Vonrhein, J.
Vonck, D. Oesterhelt, M. Grininger, Proc. Natl. Acad. Sci. USA
2008, 105, 12803 – 12808.
[6] K. B. Herath, A. B. Attygalle, S. B. Singh, J. Am. Chem. Soc.
2007, 129, 15422 – 15423.
[7] K. Herath, A. B. Attygalle, S. B. Singh, Tetrahedron Lett. 2008,
49, 5755 – 5758.
[8] a) A. Roy, F. G. Roberts, P. R. Wilderman, K. Zhou, R. J. Peters,
R. M. Coates, J. Am. Chem. Soc. 2007, 129, 12453 – 12460, and
references therein; b) M. Xu, P. R. Wilderman, R. J. Peters,
Proc. Natl. Acad. Sci. USA 2007, 104, 7397 – 7401.
[9] For a review, see: K. Tiefenbacher, J. Mulzer, Angew. Chem.
2008, 120, 2582 – 2590; Angew. Chem. Int. Ed. 2008, 47, 2548 –
2555.
[10] For some recent synthetic studies related to platensimycin, see:
a) K. C. Nicolaou, D. Pappo, K. Y. Tsang, R. Gibe, D. Y. K.
Chen, Angew. Chem. 2008, 120, 958 – 960; Angew. Chem. Int. Ed.
2008, 47, 944 – 946; b) C. H. Kim, K. P. Jang, S. Y. Choi, Y. K.
Chung, E. Lee, Angew. Chem. 2008, 120, 4073 – 4075; Angew.
Chem. Int. Ed. 2008, 47, 4009 – 4011; c) K. C. Nicolaou, A. F.
Stepan, T. Lister, A. Li, A. Montero, G. S. Tria, C. I. Turner, Y.
Tang, J. Wang, R. M. Denton, D. J. Edmonds, J. Am. Chem. Soc.
2008, 130, 13110 – 13119; d) J.-i. Matsuo, K. Takeuchi, H.
Ishibashi, Org. Lett. 2008, 10, 4049 – 4052.
[29] B. M. Trost, R. N. Bream, J. Xu, Angew. Chem. 2006, 118, 3181 –
3184; Angew. Chem. Int. Ed. 2006, 45, 3109 – 3112.
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