Stereoselective divergent synthesis of four diastereomers of pachastrissamine (Jaspine B)

Article abstract of DOI:10.1021/jo1005284

Figure presented A divergent short synthesis of four diastereomers of pachastrissamine was achieved. Natural pachastrissamine was synthesized through bis-tosylation of the common intermediate and cyclization. 2-epi- Pachastrissamine was obtained by monotosylation and spontaneous cyclization of d-ribo-phytosphingosine derivative. By use of regio- and stereospecific ring-opening reaction of the orthoester assisted by a Boc group as a key step, 3-epi- and 2,3-epi-pachastrissamines were synthesized. The three stereogenic centers of all the diastereomers were constructed by using Garners aldehyde as the sole chiral source.

Full text of DOI:10.1021/jo1005284

pubs.acs.org/joc
Stereoselective Divergent Synthesis
of Four Diastereomers of Pachastrissamine
(Jaspine B)
Yuji Yoshimitsu, Shinsuke Inuki, Shinya Oishi,
Nobutaka Fujii,* and Hiroaki Ohno*
Graduate School of Pharmaceutical Sciences, Kyoto
University, Sakyo-ku, Kyoto 606-8501, Japan
FIGURE 1. Pachastrissamine and its diastereomers.
nfujii@pharm.kyoto-u.ac.jp; hohno@pharm.kyoto-u.ac.jp
Received March 20, 2010
reported,1d,2,3 including our synthesis based on bis-cycliza-
tion of bromoallene,2s whereas less attention was given to
its epimers 2-4. Actually, 2-epi- (2), 3-epi- (3), and 2,3-epi-
pachastrissamine (4) have been synthesized by Delgado1d
and, limited to 2, by Overleeft et al.2c,k,m,r
There is significant interest concerning the molecular
mechanisms of cell death induced by pachastrissamine.
Abadie et al. indicated that pachastrissamine inhibits sphin-
gomyelin synthase and thus increases the intracellular cer-
amide level, inducing apoptotic cell death by a caspase-
dependent pathway.1c Delgado and co-workers reported
that the potency of cytotoxicity is dependent on the stereo-
chemistry of the tetrahydrofuran moiety.1d In view of eluci-
dating the effect of the stereochemistry on the biological
activity as well as the structure-activity relationship of
pachastrissamine including its stereochemistry, a useful syn-
thetic route with a high stereoselectivity and divergency is
required. This synthetic route should also aid in the production
of pachastrissamine derivatives with potentially more potent
anticancer activities. Herein, we report a stereoselective and
divergent short synthesis of four pachastrissamine diastereo-
mers from a single intermediate.
A divergent short synthesis of four diastereomers of pachas-
trissamine was achieved. Natural pachastrissamine was syn-
thesized through bis-tosylation of the common intermediate
and cyclization. 2-epi-Pachastrissamine was obtained by
monotosylation and spontaneous cyclization of D-ribo-
phytosphingosine derivative. By use of regio- and stereo-
specific ring-opening reaction of the orthoester assisted by a
Boc group as a key step, 3-epi- and 2,3-epi-pachastrissamines
were synthesized. The three stereogenic centers of all the
diastereomers were constructed by using Garner’s aldehyde
as the sole chiral source.
(2) For previous syntheses, see: (a) Sudhakar, N.; Kumar, A. R.;
Prabhakar, A.; Jagadeesh, B.; Rao, B. V. Tetrahedron Lett. 2005, 46, 325–
327. (b) Bhaket, P.; Morris, K.; Stauffer, C. S.; Datta, A. Org. Lett. 2005, 7,
875–876. (c) van den Berg, R.; Boltje, T.; Verhagen, C.; Litjens, R.; Vander
Marel, G.; Overkleeft, H. J. Org. Chem. 2006, 71, 836–839. (d) Du, Y.; Liu, J.;
Linhardt, R. J. J. Org. Chem. 2006, 71, 1251–1253. (e) Liu, J.; Du, Y.; Dong,
X.; Meng, S.; Xiao, J.; Cheng, L. Carbohydr. Res. 2006, 341, 2653–2657. (f)
Ribes, C.; Falomir, E.; Carda, M.; Marco, J. A. Tetrahedron 2006, 62, 5421–
5425. (g) Lee, T.; Lee, S.; Kwak, Y. S.; Kim, D.; Kim, S. Org. Lett. 2007, 9,
429–432. (h) Reddy, L. V. R.; Reddy, P. V.; Shaw, A. K. Tetrahedron:
Asymmetry 2007, 18, 542–546. (i) Ramana, C. V.; Giri, A. G.; Suryawanshi,
S. B.; Gonnade, R. G. Tetrahedron Lett. 2007, 48, 265–268. (j) Prasad, K. R.;
Chandrakumar, A. J. Org. Chem. 2007, 72, 6312–6315. (k) Abraham, E.;
Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.; Nicholson, R. L.; Roberts,
P. M.; Russell, A. J.; Snchez-Fernndez, E. M.; Smith, A. D.; Thomson, J. E.
Tetrahedron: Asymmetry 2007, 18, 2510–2513. (l) Yakura, T.; Sato, S.;
Yoshimoto, Y. Chem. Pharm. Bull. 2007, 55, 1284–1286. (m) Abraham, E.;
Brock, E. A.; Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.; Nicholson,
R. L.; Perkins, J. H.; Roberts, P. M.; Russell, A. J.; Snchez-Fernndez, E. M.;
Scott, P. M.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2008, 6, 1665–
1673. (n) Passiniemi, M.; Koskinen, A. M. P. Tetrahedron Lett. 2008, 49,
980–983. (o) Venkatesan, K.; Srinivasan, K. V. Tetrahedron: Asymmetry
2008, 19, 209–215. (p) Enders, D.; Terteryan, V.; Palecek, J. Synthesis 2008,
2278–2282. (q) Ichikawa, Y.; Matsunaga, K.; Masuda, T.; Kotsuki, H.;
Nakano, K. Tetrahedron 2008, 64, 11313–11318. (r) Reddipalli, G.; Venka-
taiah, M.; Mishra, M. K.; Fadnavis, N. W. Tetrahedron: Asymmetry 2009,
20, 1802–1805. (s) Inuki, S.; Yoshimitsu, Y.; Oishi, S.; Fujii, N.; Ohno, H.
Org. Lett. 2009, 11, 4478–4481. (t) Jayachitra, G.; Sudhakar, N.; Ravi
Kumar Anchoori, B.; Venkateswara, R.; Sayantani, R.; Rajkumar, B.
Synthesis 2010, 115–119.
In 2002, pachastrissamine (1) (Figure 1), the first natu-
rally occurring anhydrophytosphingosine derivative, was
isolated from the Okinawan marine sponge Pachastrissa
sp.1a Shortly thereafter, a French research group isolated
the same compound from the Vanuatuan marine sponge
Jaspis sp. and named the compound jaspine B.1b Pachas-
trissamine exhibits marked submicromolar cytotoxity
against several cancer cell lines.1 Due to its impressive
biological activity, and simple and unique structure, seve-
ral total syntheses of pachastrissamine (1) have been
(1) (a) Kuroda, I.; Musman, M.; Ohtani, I.; Ichiba, T.; Tanaka, J.;
Garcia-Gravalos, D.; Higa, T. J. Nat. Prod. 2002, 65, 1505–1506. (b) Ledroit,
V.; Debitus, C.; Lavaud, C.; Massoit, G. Tetrahedron Lett. 2003, 44, 225–
ꢀ
228. (c) Salma, Y.; Lafont, E.; Therville, N.; Carpentier, S.; Bonnafe, M. J.;
Levade, T.; Genisson, Y.; Abadie, N. A. Biochem. Pharmacol. 2009, 78, 477–
ꢀ
ꢁ
485. (d) Canals, D.; Mormeneo, D.; Fabrias, G.; Llebaria, A.; Casas, J.;
Delgado, A. Bioorg. Med. Chem. 2009, 17, 235–241.
(3) For a review, see: Abraham, E.; Davies, S. G.; Roberts, P. M.; Russell,
A. J.; Thomson, J. E. Tetrahedron: Asymmetry 2008, 19, 1027–1047.
DOI: 10.1021/jo1005284
r
Published on Web 04/21/2010
J. Org. Chem. 2010, 75, 3843–3846 3843
2010 American Chemical Society

Yoshimitsu et al.
SCHEME 2. Preparation of the Common Intermediate 6a
JOCNote
SCHEME 1. Strategy for Stereoselective Divergent Synthesis
of Four Pachastrissamine Diastereomers
SCHEME 3. Unsuccessful Tetrahydrofuran Formation via
Orthoester
Our synthetic plan is depicted in Scheme 1. We envisaged diol
6a,4 which can be easily prepared from Garner’s aldehyde 55 in
two steps, as a common intermediate for the synthesis of all the
diastereomers.6 Thus, the removal of the acetonide of 6a would
furnish the D-ribo-phytosphingosine derivative 7a, which could
be converted into 7b by stereoinversion at C-3. We expected
that these amino triol derivatives 7a and 7b would be good
precursors of 1-4: conversion of the C-4 hydroxy group in 7a
or 7b into a leaving group would lead to nucleophilic attack by
the C-1 hydroxy group to give 1 or 3 (Scheme 1, path A).
Conversely, nucleophilic cyclization by use of the C-1 hydroxy
group as the leaving group would give 2 or 4 (Scheme 1, path
B). The key to the success of this strategy would be the efficient
stereoinversion of 7a at C-3 and the regioselective activation/
cyclization at C-4 (path A).
Preparation of the requisite diol 6a was already described
by Ogino and co-workers.4 We synthesized 6a by use of a
slightly modified protocol for improvement of the yields in each
step (Scheme 2). Garner’s aldehyde was converted into the
(Z)-olefin 8 in 92% yield with 13:1 selectivity by treatment with
a phosphonium ylide derived from C15H31PPh3Br.4 In good
accordance with Ogino’s observation, dihydroxylation of 8
with OsO4 in the presence of N-methylmorphorine N-oxide
gave a diastereomeric mixture of the diol 6a and 6b, which can
be separated by column chromatography.
2-azide-1,3,4-triol derivative reported by Overkleeft et al.2c,7
Unfortunately, when 7a was treated under the same reaction
conditions as reported, we obtained oxazolidinone 10 in 58%
yield,8 formed by participation of a carbamate in the intramo-
lecular nucleophilic reaction instead of the C-1 hydroxy group.
However, this reaction clearly shows a potential strategy for
regioselective inversion at the C-3 position (vide infra).
We next examined regioselective protection of the C-3
hydroxy group of 6a. We expected that the formation of the
oxazolidinone of type 13 would be useful for this purpose
(Scheme 4). However, the reaction of 6a with t-BuOK in
THF selectively promoted oxazinanone formation leading to
12. Other basic conditions were also ineffective.9,10
We decided to utilize bis-tosylate 14 as a cyclization
precursor (Scheme 5). The diol 6a was converted into the
corresponding bis-tosylate 14 with TsCl, Et3N, and Me3N
3
HCl.11 Treatment of 14 with TsOH H2O in MeOH at 70 °C
3
successfully produced the desired tetrahydrofuran 15 in
(7) For the pioneering work on the Lewis acid-mediated THF ring forma-
tion of triol derivatives via orthoester formation, see: Zheng, T.; Narayan, R. S.;
Schomaker, J. M.; Borhan, B. J. Am. Chem. Soc. 2005, 127, 6946–6947.
(8) Formation of unidentified byproduct was observed. Protection of the
primary hydroxy group as silyl ether (18, Scheme 7) suppressed formation of
the side products to give 20 in excellent yield.
With the common intermediate 6a in hand, we first examined
synthesis of natural pachastrissamine (1) (Scheme 3). The aceto-
nide group was removed by using a catalytic amount of
(9) The reaction of the corresponding silyl ether 26 with t-BuOK gave the
silyl migration products 27 and 28 (see the Supporting Information).
TsOH H2O in MeOH to give the triol 7a. We then tried to
3
construct the desired tetrahydrofuran core by orthoester-
mediated tetrahydrofuran formation, a related reaction of the
(4) Azuma, H.; Tamagaki, S.; Ogino, K. J. Org. Chem. 2000, 65, 3538–
3541. They synthesized (Z)-8 in 66% yield (C15H31PPh3Br, LHMDS, -78
°C) and 6a and 6b in 55% and 19% respective yield (cat. OsO4, NMO,
t-BuOH/H2O).
(5) (a) Garner, P. Tetrahedron Lett. 1984, 25, 5855–5858. (b) Campbell,
A. D.; Raynham, T. M.; Taylor, R. J. K. Synthesis 1998, 1707–1709.
(6) For the synthesis of pachastrissamine derivatives from Garner’s
aldehyde, see refs 2a 2n, and 2s.
(10) A related oxazinanone formation was reported; see: Komatsu, Y.;
Ikishima, H.; Okuyama, A.; Nakamura, M.; Kotsuki, H. Synth. Org. Chem.
Jpn. 2009, 67, 65–75.
(11) Tanabe, Y.; Yamamoto, H.; Yoshida, Y.; Miyawaki, T.; Utsumi, N.
Bull. Chem. Soc. Jpn. 1995, 68, 297–300.
3844 J. Org. Chem. Vol. 75, No. 11, 2010

Yoshimitsu et al.
JOCNote
SCHEME 4. Unsuccessful Protection of 3-OH by
Oxazolidinone Formation
SCHEME 7. Synthesis of 3-epi-Pachastrissamine (3)
SCHEME 5. Synthesis of Pachastrissamine (1)
SCHEME 8. Synthesis of 2,3-epi-Pachastrissamine (4)
SCHEME 6. Synthesis of 2-epi-Pachastrissamine (2)
92% yield. This reaction proceeds through initial removal
of acetonide and Boc groups followed by intramolecular
nucleophilic displacement at the C-4 position.12 Pachas-
trissamine (1) was obtained by the cleavage of the tosyl
group with Mg in MeOH.
2-epi-Pachastrissamine (2) was then prepared in analogy
with the reported procedure (Scheme 6).1d,2c Regioselective
tosylation of the primary hydroxy group of the D-ribo-phyto-
sphingosine derivative 7a prompted spontaneous cyclization
to give the tetrahydrofuran derivative 17. Removal of the Boc
group with TFA provided the desired product, 2-epi-pachas-
trissamine (2).
Next, the synthesis of 3-epi-pachastrissamine (3) was attem-
pted, which requires regioselective inversion of the C-3 stereo-
genic center. We envisioned that this challenging issue can
be addressed by foregoing the regio- and stereospecific ring-
opening reaction of the orthoester assisted by the neighboring
Boc-amide group, followed by loss of isobutene and decarbo-
nylation under basic conditions (Scheme 3). The primary
hydroxy group of 7a was protected by using TIPSCl in the pre-
sence of imidazole to give the silyl ether 18 (Scheme 7). Reaction
of 18 with MeC(OMe)3 in the presence of a catalytic amount
followed by regioselective nucleophilic attack of the Boc oxy-
gen toward C-3. Protection of the carbamate nitrogen of 20
with Boc2O and alcoholysis of the oxazolidinone successfully
provided 21, the C-3 epimer of 18. Similar to the synthesis of 1
(Scheme 3), bis-tosylation, desilylation, and tetrahydrofuran
formation promoted by TBAF afforded the desired tetrahy-
drofuran 23. Finally, successive removal of the tosyl and Boc
groups led to 3-epi-pachastrissamine (3).1d
The final stage was set for the synthesis of 2,3-epi-pachas-
trissamine 4 (Scheme 8).1d The silyl ether of 21 was cleaved
with TBAF in THF to give the cyclization precursor 7b.
Selective monotosylation of the primary hydroxy group
followed by base treatment afforded tetrahydrofuran 25.
Finally, the Boc group was removed with TFA in CH2Cl2 to
give 2,3-epi-pachastrissamine (4). The spectroscopic data
and optical rotation of all diastereomers 1-4 were in good
agreement with those reported previously.1-3
In conclusion, we have developed a stereoselective diver-
gent synthesis of four pachastrissamine diastereomers using
Garner’s aldehyde as the sole chiral pool. Further research
including biological assays and structure-activity relation-
ships are currently underway and will be reported elsewhere.
of BF3 OEt2 in CH2Cl2 directly afforded the desired oxazoli-
3
dinone 20 in excellent yield, through orthoester formation
(12) For a related THF formation under acidic conditions, see: Armin,
B.; Jens, H.; Jacques, W.; Henri, B. K. J. Org. Chem. 1993, 58, 6814–6817.
J. Org. Chem. Vol. 75, No. 11, 2010 3845

Yoshimitsu et al.
JOCNote
Experimental Section
dried over MgSO4. The filtrate was concentrated under reduced
pressure to give a white solid, which was purified by flash
chromatography over silica gel with CHCl3-MeOH-28%
NH4OH (95:4:1) to give 1 as a white solid (29 mg, 81% yield):
mp 95-97 °C; [R]25D þ14.8 (c 0.57, EtOH), [lit.3 [R]D þ13.3-19.0
tert-Butyl (S)-4-[(1S,2R)-1,2-Bis(tosyloxy)hexadecyl]-2,2-di-
methyloxazolidine-3-carboxylate (14). To a stirred solution of
6a (293 mg, 0.640 mmol) in CH2Cl2 (1.3 mL) were added Et3N
(887 μL, 6.40 mmol), TsCl (610 mg, 3.20 mmol), and Me3N HCl
1
3
(EtOH)]; IR (neat) 3341 (NH and OH); H NMR (500 MHz,
(61 mg, 0.638 mmol) at room temperature. After stirring for 2 d
at this temperature, the whole was extracted with CH2Cl2. The
extract was washed with saturated NH4Cl and brine, then dried
over MgSO4. The filtrate was concentrated under reduced
pressure to give an oily residue, which was purified by flash
chromatography over silica gel with n-hexane-EtOAc (10:1) to
CDCl3) δ 0.88 (t, J = 6.9 Hz, 3H), 1.20-1.49 (m, 24H), 1.59-
1.73 (m, 2H), 1.80-2.20 (br s, 2H), 3.52 (dd, J = 8.5, 7.1 Hz, 1H),
3.60-3.70 (m, 1H), 3.73 (ddd, J = 7.1, 7.1, 3.4 Hz, 1H), 3.87 (dd,
J=4.6, 3.4 Hz, 1H), 3.92 (dd, J = 8.5, 7.3 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 14.1, 22.7, 26.3, 29.3, 29.4, 29.6 (6C),
29.7, 29.8, 31.9, 54.3, 71.8, 72.4, 83.2. Anal. Calcd for C18H37-
NO2: C, 72.19; H, 12.45; N, 4.68. Found: C, 72.40; H, 12.18;
N, 4.39.
give 14 as a colorless oil (417 mg, 85% yield): [R]25 -21.7
D
(c 0.84, CHCl3); IR (neat) 1689 (CdO), 1365 (OSO2), 1176
(OSO2); 1H NMR (500 MHz, CDCl3) δ 0.88 (t, J = 6.9 Hz, 3H),
1.08-1.33 (m, 26H), 1.44 (s, 6H), 1.49 (s, 9H), 2.41 (s, 3H), 2.43
(s, 3H), 3.84 (dd, J = 9.2, 6.9 Hz, 1H), 3.93 (dd, J = 9.2, 2.9 Hz,
1H), 4.05 (m, 1H), 4.68 (m, 1H), 5.21 (m, 1H), 7.26 (d, J = 8.0
Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 7.78
(d, J = 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 14.0, 21.5
(2C), 22.6, 25.1 (2C), 28.4 (3C), 28.9, 29.2, 29.3, 29.4, 29.6 (4C),
29.7 (3C), 31.9, 56.5, 63.5, 80.1, 80.8, 82.8, 94.0, 127.9 (4C),
128.2 (4C), 129.7 (2C), 134.1 (2C), 144.7; HRMS (FAB) calcd
for C40H63NNaO9S2 (MNaþ) 788.3842, found 788.3835.
(2S,3S,4S)-4-Amino-2-tetradecyltetrahydrofuran-3-yl 4-Methyl-
benzenesulfonate (15). To a stirred solution of 14 (92 mg, 0.120
(R)-{(4S,5R)-2-Oxo-4-[(triisopropylsilyloxy)methyl]oxazolidin-5-
yl}pentadecyl Acetate (20). To a stirred solution of 18 (352 mg,
0.614 mmol) in CH2Cl2 (61 mL) were added MeC(OMe)3 (460 μL,
3.68 mmol) and BF3 OEt2 (15 μL, 0.122 mmol) at 0 °C, then the
3
mixture was stirred for 1.5 h at room temperature. The mixture was
quenched by addition of MeOH at 0 °C, and concentrated under
reduced pressure to give an oily residue, which was purified by flash
chromatography over silica gel with n-hexane-EtOAc (4:1) to give
20 as a colorless oil (318 mg, 96% yield): [R]25 -25.5 (c 0.81,
D
CHCl3); IR (neat) 3305 (NH), 1746 (CdO); 1H NMR (500 MHz,
CDCl3) δ 0.88 (t, J = 6.9 Hz, 3H), 1.05 (d, J = 5.7 Hz, 18H),
1.08-1.14(m, 2H), 1.22-1.37 (m, 24H), 1.63-1.75 (m, 3H), 2.10 (s,
3H), 3.61-3.67 (m, 1H), 3.67-3.73 (m, 2H), 4.44 (dd, J = 4.6, 3.4
Hz, 1H), 5.00 (ddd, J= 6.9, 6.9, 3.4 Hz, 1H), 5.95 (s, 1H); 13CNMR
(125MHz,CDCl3) δ11.8, 14.0, 17.8 (6C), 20.8, 22.6 (3C), 25.2, 29.2,
29.3, 29.4, 29.5, 29.6 (6C), 29.9, 55.5, 65.0, 73.3, 78.7, 159.0, 170.6;
HRMS (FAB) calcd for C30H60NO5Si (MHþ) 542.4235, found
542.4241.
mmol) in MeOH (4.0 mL) was added TsOH H2O (23 mg, 0.121
3
mmol) at 70 °C. After stirring for 8 h at this temperature, the
mixture was concentrated under reduced pressure to give an oily
residue, which was purified by flash chromatography over silica gel
with CHCl3-MeOH-28% NH4OH (95:4:1) to give 15 as a white
solid (50 mg, 92% yield): mp 65-66 °C; [R]25 þ18.2 (c 1.85,
D
1
CHCl3); IR (neat) 1362 (OSO2), 1175 (OSO2); H NMR (500
MHz, CDCl3) δ 0.88 (t, J = 6.9 Hz, 3H), 1.02-1.32 (m, 26H),
1.32-1.48 (m, 2H), 2.46 (s, 3H), 3.43 (dd, J = 8.6, 8.6 Hz, 1H),
3.72 (ddd, J = 8.6, 8.6, 4.6 Hz, 1H), 3.88 (ddd, J = 4.6, 4.6, 4.0 Hz,
1H), 3.99 (dd, J = 8.6, 8.6 Hz, 1H), 4.85 (dd, J = 4.6, 4.6 Hz, 1H),
7.36 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.0 Hz, 2H); 13C NMR (125
MHz, CDCl3) δ 14.0, 21.5, 22.6, 25.8, 29.3, 29.4, 29.5 (2C), 29.6
(5C), 29.8, 31.9, 55.3, 71.3, 81.1, 84.2, 127.8 (2C), 129.9 (2C), 133.9,
145.0; HRMS (FAB) calcd for C25H44NO4S (MHþ) 454.2986,
found 454.2982.
(2S,3S,4S)-4-Amino-2-tetradecyltetrahydrofuran-3-ol (Pachas-
trissamine) (1). To a stirred mixture of 15 (54 mg, 0.119 mmol) in
MeOH (2.4 mL) was added Mg (58 mg, 2.39 mmol) at room
temperature. After stirring for 1.5 h at this temperature, the
mixture was concentrated under reduced pressure, then the
residue was diluted with CH2Cl2, washed with 2 N NaOH, and
Acknowledgment. This work was supported by a Grant-
in-Aid for Encouragement of Young Scientists (A) (H.O.)
from the Ministry of Education, Culture, Sports, Science
and Technology of Japan, and Targeted Proteins Research
Program. Appreciation is expressed to the Fundamental Studies
in Health Sciences of the National Institute of Biomedical
Innovation (NIBIO). S.I. is grateful for Research Fellowships
from the Japan Society for the Promotion of Science (JSPS) for
Young Scientists.
Supporting Information Available: Experimental procedures
and characterization data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
3846 J. Org. Chem. Vol. 75, No. 11, 2010