First total syntheses and spectral data corrections of 11-α- methoxycurvularin and 11-β-methoxycurvularin

Article abstract of DOI:10.1021/jo701885n

(Chemical Equation Presented) Concise and efficient total syntheses of 11-α-methoxycurvularin and 11-β-methoxycurvularin were accomplished for the first time. The three-component linchpin coupling and intramolecular acylation reactions were key steps, in which we found the spectral data of 11-α-methoxycurvularin and 11-β-methoxycurvularin, reported in the literature, were reversed with each other.

Full text of DOI:10.1021/jo701885n

First Total Syntheses and Spectral Data
Corrections of 11-r-Methoxycurvularin and
11-â-Methoxycurvularin
Qiren Liang,† Yongquan Sun,† Binxun Yu,†
Xuegong She,*,†,‡ and Xinfu Pan*,†
Department of Chemistry, State Key Laboratory of Applied
Organic Chemistry, Lanzhou UniVersity, Lanzhou, 730000,
People’s Republic of China, State Key Laboratory for Oxo
Synthesis and SelectiVe Oxidation, Lanzhou Institute of
Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, People’s Republic of China
FIGURE 1. Curvularin (1), 11-R-hydroxycurvularin (2), 11-â-
hydroxycurvularin (3), 11-R-methoxycurvularin (4), and 11-â-meth-
oxycurvularin (5).
shexg@lzu.edu.cn
ReceiVed August 28, 2007
compounds 4 and 5 feature a 12-membered macrolide lactone
containing a fused 1,3-dihydroxybenzene ring. The absolute
configurations of 11-R-methoxycurvularin and 11-â-methoxy-
curvularin were assigned as (11S,15S) and (11R,15S) by
1
comparing the H NMR data with those of 11-R-hydroxycur-
vularin 2 and 11-â-hydroxycurvularin 3, respectively.1 Their
favorable bioactivities as well as interesting structures inspired
our syntheses of 4 and 5 using a process that would be flexible
enough to provide suitable derivatives for later SAR experi-
ments. Herein, we wish to report the concise total syntheses of
4 and 5 together with revisions of the spectral data of the natural
products, 11-R-methoxycurvularin and 11-â-methoxycurvularin.
Retrosynthetic analysis of macrolide 4 is depicted in Scheme
1. We envisioned that macrolide 4 could be available from acid
15a by the intramolecular acylation. In turn acid 15a might be
prepared from 10a and 3,5-dimethoxyphenylacetic acid 12
through several transformations. As the key strategic step, a
one-flask three-component linchpin coupling reaction of (S)-
(-)-methyloxirane 8, benzyl ether of (R)-1,2-epoxy-4-butanol
7a, and dithianes 9 would provide the desired adduct 10a.
A three-component, one-flask linchpin coupling employing
2-tert-(butyldimethylsilyl)-1,3-dithiane with two different ep-
oxide electrophiles to construct unsymmetrical adducts exploited
a solvent-controlled Brook rearrangement (Scheme 2).6 This
route leads to the rapid, efficient, and stereocontrolled assembly
of highly functionalized intermediates for complex molecule
synthesis.7 In this note, we report the application of this tactic
for the efficient construction of the target molecule 4.
Concise and efficient total syntheses of 11-R-methoxycur-
vularin and 11-â-methoxycurvularin were accomplished for
the first time. The three-component linchpin coupling and
intramolecular acylation reactions were key steps, in which
we found the spectral data of 11-R-methoxycurvularin and
11-â-methoxycurvularin, reported in the literature, were
reversed with each other.
11-R-Methoxycurvularin and 11-â-methoxycurvularin are
members of the curvularin family isolated from the mycelium
of the hybrid strain ME 005 derived from penicillium citreo-
viride 4692 and 6200 (Figure 1).1 They were discovered to have
considerable cytotoxicity toward a panel of four human cancer
cell lines [NCI-H460, MCF-7, SF-268, MIA. Pa Ca-2].2 Also,
they have been reported to inhibit sea urchin embryogenesis
by acting on components of the mitotic apparatus,3 90 (HSP90),4
a promising target for anticancer drug discovery.5 Structurally,
(6) (a) Smith, A. B., III; Boldi, A. M. J. Am. Chem. Soc. 1997, 119,
6925. (b) Smith, A. B., III; Pitram, S. M.; Boldi, A. M.; Gaunt, M. J.;
Sfouggatakis, C.; Moser, W. H. J. Am. Chem. Soc. 2003, 125, 14435.
(7) (a) Smith, A. B., III; Zhuang, L.; Brook, C. S.; Boldi, A. M.; McBriar,
M. D.; Moser, W. H.; Murase, N.; Nakayama, K.; Verhoest, P. R.; Lin, Q.
Tetrahedron Lett. 1997, 38, 8667. (b) Smith, A. B., III; Zhuang, L.; Brook,
C. S.; Lin, Q.; Moser, W. H.; Trout, R. E. L.; Boldi, A. M. Tetrahedron
Lett. 1997, 38, 8671. (c) Smith, A. B., III; Lin, Q.; Nakayama, K.; Boldi,
A. M.; Brook, C. S.; McBriar, M. D.; Moser, W. H.; Sobukawa, M.; Zhuang,
L. Tetrahedron Lett. 1997, 38, 8675. (d) Smith, A. B., III; Pitram, S. M.
Org. Lett. 1999, 1, 2001. (e) Smith, A. B., III; Doughty, V. A.; Sfouggatakis,
C.; Bennett, C. S.; Koyanagi, J.; Takeuchi, M. Org. Lett. 2002, 4, 783. (f)
Smith, A. B., III; Pitram, S. M.; Fuertes, M. J. Org. Lett. 2003, 5, 2751. (g)
Smith, A. B., III; Pitram, S. M.; Boldi, A. M.; Gaunt, M. J.; Sfouggatakis,
C.; Moser, W. H. J. Am. Chem. Soc. 2003, 125, 14435. (h) Smith, A. B.,
III; Kim, D. Org. Lett. 2004, 6, 1493-1495.
† Lanzhou University.
‡ Chinese Academy of Science.
(1) Lai, S.; Shizuri, Y.; Yamamura, S.; Kawai, K.; Furukawa, H. Bull.
Chem. Soc. Jpn. 1991, 64, 1048-1050.
(2) (a) He, J.; Wijeratne, E. M. K.; Bashyal, B. P.; Zhan, J.; Seliga, C.
J.; Liu, M. X.; Pierson, E. E.; Pierson, L. S., III; VanEtten, H. D.; Gunatilaka,
A. A. L. J. Nat. Prod. 2004, 67, 1985-1991. (b) Zhan, J.; Wijeratne, E.
M. K.; Seliga, C. J.; Pierson, E. E.; Pierson, L. S., III; VanEtten, H. D.;
Gunatilaka, A. A. L. J. Antibiot. 2004, 57, 341-344.
(3) Kobayashi, A.; Hino, T.; Yata, S.; Itoh, T. J.; Sato, H.; Kawazu, K.
Agric. Biol. Chem. 1988, 52, 3119-3123.
(4) Matsushita, N.; Akinaga, S.; Agatsuma, T. International Patent No.
Wo 2004/024141, 2004.
(5) Whitesell, L.; Bagatell, R.; Falsey, R. Curr. Cancer Drug Targets
2003, 3, 349-358.
10.1021/jo701885n CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/08/2007
9846
J. Org. Chem. 2007, 72, 9846-9849

SCHEME 1. Retrosynthetic Analysis of Compound 4
carboxylic acid 15a in a mixture of TFA and TFAA.14
Deprotection of the methoxy groups at C5 and C7 of macrolide
16a with freshly prepared AlI3 completed the synthesis of (11S,-
15S)-4 (i.e., 11-R-methoxycurvularin).15 However, the 1H NMR
(400 MHz, CDCl3) and optical rotation of the synthetic 4 were
in disagreement with that of the reported natural product 11-
R-methoxycurvularin, though identical with the reported 11-â-
methoxycurvularin epimer.1 To further confirm the experimental
results, (11R,15S)-5 (i.e., 11-â-methoxycurvularin) was synthe-
sized by using the same strategy as the synthesis of 4 from (S)-
1,2-epoxy-4-butanol 6 (prepared from (S)-(-)-malic acid ac-
cording to Kenji Mori)8 and (S)-8 (see the Supporting
Information). As expected the spectral data of 5 (1H NMR and
optical rotation) were identical with those previously reported
for 11-R-methoxycurvularin.1 Thus, we concluded that the
corresponding spectral data for the absolute configuration of
11-R-methoxycurvularin are the data reported for the natural
product 11-â-methoxycurvularin and the corresponding spectral
data for the structure of 11-â-methoxycurvularin are the data
reported for the natural product 11-R-methoxycurvularinsboth
are just opposite what is reported in the literature.
SCHEME 2. Three-Component, One-Flask Linchpin
Coupling
The synthesis of target molecule 4 commenced from (R)-
1,2-epoxy-4-butanol 6, which was prepared from (S)-(-)-malic
acid according to the route made by Kenji Mori and its NMR
data and optical rotation were identical with those reported in
the literature.8 As shown in Scheme 3, the multicomponent
linchpin coupling was employed with commercially available
(S)-(-)-methyloxirane 8 and epoxide 7a, and the latter is readily
prepared from (R)-6 with BnBr and NaH.9 Pleasingly, with
lithiation of dithiane 9 in THF n-BuLi (-78 to -10 °C) was
used, followed by the addition of epoxide (S)-8 (-78 °C),
warming to -40 °C, and stirring for an additional 1 h at
-40 °C, and then adding HMPA (3 equiv) and epoxide 7a in
THF, letting it warm to 0 °C for 1 h. Last MeI (3 equiv) was
added and the mixture was stirred for 0.5 h at 0 °C, furnishing
10a in 74% isolated yield. The structure of 10a was secured by
In summary a concise and efficient total synthesis of 11-R-
methoxycurvularin and 11-â-methoxycurvularin has been ac-
complished for the first time in 8 steps with an overall yield of
10.0% and 13.3%, respectively. The hydroxy groups at C11
and C15 were efficiently constructed by using a one-flask three-
component linchpin coupling. The ring closure was achieved
by using an intramolecular Friedel-Crafts reaction.
1
careful H and 13C NMR and HRMS experiments. However,
in this transformation when we used the TBDPS ether of (R)-6
as the substrate, the products of linchpin coupling were complex
and no desired product was obtained.
With compound 10a in hand, deprotection of the TBS group
produced 11a in 99% yield.10 Esterification of 11a with 3,5-
dimethoxyphenylacetic acid 1211,12 using DCC and DMAP gave
the ester 13a in 98% yield.12 The dithiane and benzyl groups
of 13a were removed with Raney Ni under reflux for 6 h,
affording 14a in 75.4% yield.13 Oxidation of the hydroxy group
of 14a with Jones reagent (5 equiv) in acetone at 0 °C for 15
min gave the acid 15a in 86% yield.7h The macrolide 16a was
obtained by intramolecular Friedel-Crafts reaction of the
Experimental Section
Syntheses of Compounds 10a and 10b. n-Butyllithium (2.8 mL,
2.1 M in hexanes) was added to a solution of 2-tert-(butyldi-
methylsilyl)-1,3-dithiane 9 (1.404 g, 6 mmol) in 25 mL of THF at
-78 °C under Ar. The mixture was warmed to -10 °C then stirred
for 1 h, followed by cooling to -78 °C and the addition of the
(S)-(-)-methyloxirane 8 (348 mg, 6 mmol) in 2 mL of THF.
Completion of the first alkylation was achieved in 1 h at -40 °C.
The mixture was cooled to -78 °C and HMPA (3.2 g, 18 mmol)
was added, warming the mixture to -40 °C and stirring for 10
min. The mixture was recooled to -78 °C and the second epoxide
7a (1.28 g, 7.2 mmol) in 10 mL of THF was added. The mixture
was stirred at 0 °C for 1 h, then MeI (2.56 g, 18 mmol) was added
and the mixture was stirred at 0 °C for 0.5 h. The reaction was
quenched with saturated NH4Cl and extracted with ether (3 × 60
(8) Mori, K.; Ikunaka, M. Tetrahedron 1983, 40, 3471-3479.
(9) (a) Czernecki, S.; Georgoulis C.; Provelenghiou, C. Tetrahedron Lett.
1976, 3535. (b) Kanai, K.; Sakamoto, I.; Ogawa, S.; Suami, T. Bull. Chem.
Soc. Jpn. 1987, 60, 1529.
(10) Silverman, R. B.; Lu, X.; Banik, G. M. J. Org. Chem. 1992, 57,
6617-6622.
(11) Baker, P. M.; Bycroft, B. W.; Roberts, J. C. J. Chem. Soc. (C) 1967,
1913.
(12) Liang, Q.; Zhang, J.; Quan, W.; Sun, Y.; She, X.; Pan, X. J. Org.
Chem. 2007, 72, 2694-2697.
(13) Ito, H.; Takeguchi, S.; Kawagishi, T.; Iguchi, K. Org. Lett. 2006,
8, 4883-4885.
(14) (a) Bracher, F.; Schulte, B. Liebigs Ann. Recl. 1997, 1979. (b) Liang,
Q.; Zhang, J.; Quan, W.; Sun, Y.; She, X.; Pan, X. J. Org. Chem. 2007,
72, 2694-2697. (c) Bringmann, G.; Lang, G.; Michel, M.; Heubes, M.
Tetrahedron Lett. 2004, 45, 2829.
(15) Kreipl, A. T.; Reid, C.; Steglich, W. Org. Lett. 2002, 4, 3287.
J. Org. Chem, Vol. 72, No. 25, 2007 9847

SCHEME 3 a
a Reagents and conditions: (a) NaH, BnBr, Bu4N+I-, THF, rt, 99%; (b) n-BuLi, HMPA, MeI, THF, -78 °C to 0 °C, 74%; (c) HCl (1% solution in
MeOH), rt, 99%; (d) DCC, DMAP, Et2O, rt, 4 h, 98%; (e) Raney Ni, H2, EtOH, 80 °C, 8h, 75%; (f) Jones regent, 0 °C, 15 min, 86%; (g) TFA, TFAA, rt,
8 h, 42%; (h) AlI3, Bu4N+I-, Ph, 10 °C, 15 min, 68%.
mL), and the combined organic solutions were washed with brine
(3 × 15 mL), dried (Na2SO4), and concentrated in vacuo. The
residue was purified by column chromatography (hexanes/EtOAc,
1H NMR (300 MHz, CDCl3) δ 6.49 (d, J ) 1.8 Hz, 1H), 6.42 (d,
J ) 1.8 Hz, 1H), 6.27 (d, J ) 15.9 Hz, 1H), 4.89 (t, J ) 6.3 Hz,
1H), 3.86 (s, 2H), 3.83 (s, 3H), 3.75 (s, 3H), 3.37 (d, J ) 4.2 Hz,
3H), 2.35 (dd, J ) 12.9 Hz, 6.3 Hz, 1H), 2.19 (dd, J ) 15.9 Hz,
8.4 Hz, 1H), 1.41-1.58 (m, 4H), 1.16 (d, J ) 6.6 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 198.4, 170.5, 161.7, 158.9, 156.3, 133.3,
132.9, 122.5, 106.6, 97.7, 72.9, 55.9, 55.6, 55.4, 39.6, 34.3, 34.1,
24.4, 20.3; IR (KBr) 3380, 2929, 1725, 1655, 1602, 1458, 1312,
1156, 1085 cm-1; HRMS m/z calcd for C19H26O6 [M + Na]+
373.1627, found 373.1622.
50:1) to give compound 10a (2.15 g, 74%) as a colorless oil: [R]25
D
-5 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.26-7.37 (m,
5H), 4.51 (dd, J ) 14.1 Hz, 11.7 Hz, 2H), 4.18 (dd, J ) 9.9 Hz,
5.7 Hz, 1H), 3.67 (dd, J ) 9.9 Hz, 5.7 Hz, 1H), 3.58 (dd, J ) 6.9
Hz, 5.7 Hz, 2H), 3.31 (s, 3H), 3.27-3.80 (m, 4H), 2.13-2.22 (m,
3H), 2.05 (dd, J ) 15.0 Hz, 3.6 Hz, 1H), 1.87-1.94 (m, 4H), 1.22
(dd, J ) 6.6 Hz, 3H), 0.84 (d, J ) 5.1 Hz, 9H), 0.09 (d, J ) 5.1
13C
Hz, 6H);
NMR (75 MHz, CDCl3) δ 128.3, 127.7, 127.5, 76.0,
15b (200 mg, 0.54 mmol) was treated with 10 mL of TFA and
73.0, 66.9, 66.3, 56.3, 51.9, 49.2, 44.6, 34.6, 26.4, 26.1, 26.0, 25.0,
18.0, -4.0, -4.1; IR (KBr) 3388, 2929, 2855, 1457, 1366, 1252,
1095, 1002, 833, 755 cm-1; HRMS m/z calcd for C25H44S2O3Si
[M + Na]+ 507.2393, found 507.2387.
The title compound 10b (7.53 g, 76%) was obtained from (S)-
(-)-methyloxirane 8 (1.16 g, 20 mmol), (R)-2-(2-(benzyloxy)ethyl)-
oxirane 7b (4.272 g, 24 mmol), 2-tert-(butyldimethylsilyl)-1,3-
dithiane 9 (4.68 g, 20 mmol), HMPA (10.74 g, 60 mmol), and MeI
2 mL of TFAA as described for the synthesis of 16a to give 16b
1
(39 mg, 20%) as a colorless oil: [R]25 -36 (c 0.9, CHCl3); H
D
NMR (300 MHz, CDCl3) δ 6.48 (s, 1H), 6.40 (s, 1H), 6.25 (d, J )
15.6 Hz, 1H), 4.88 (t, J ) 6.3 Hz, 1H), 3.83 (s, 2H), 3.82 (s, 3H),
3.73 (s, 3H), 3.33 (d, J ) 18.6 Hz, 3H), 2.32 (t, J ) 6.9 Hz, 1H),
2.18 (t, J ) 6.9 Hz, 1H), 1.75-1.90 (m, 2H), 1.37-1.53 (m. 4H),
1.15 (d, J ) 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 198.5,
170.5, 160.9, 157.5, 156.5, 133.2, 132.8, 122.5, 106.5, 97.8, 72.9,
55.8, 55.6, 55.4, 39.5, 34.2, 34.1, 24.4, 20.3; IR (KBr) 3380, 2929,
1724, 1655, 1603, 1458, 1312, 1157, 1084 cm-1; HRMS m/z calcd
for C19H26O6 [M + H]+ 351.1808, found 351.1801.
(8.52 g, 60 mmol) by the same operation as the synthesis of 10a:
1
[R]25 -10 (c 1.7, CHCl3); H NMR (300 MHz, CDCl3) δ 7.26-
D
7.37 (m, 5H), 4.51 (dd, J ) 14.1 Hz, 11.7 Hz, 2H), 4.19 (dd, J )
11.7 Hz, 5.4 Hz, 1H), 3.69 (t, J ) 6.0 Hz, 1H), 3.58 (td, J ) 6.0
Hz, 2.4 Hz, 2H), 3.32 (s, 3H), 2.71-2.80 (m, 4H), 2.07-2.23
(m, 4H), 1.84-1.94 (m, 4H), 1.25 (d, J ) 6.0 Hz, 3H), 0.89 (t, J
) 3.0 Hz, 9H), 0.08 (t, J ) 3.0 Hz, 6H); 13C NMR (75 MHz,
CDCl3) δ 138.4, 128.3, 127.7, 127.5, 76.0, 73.0, 67.0, 66.4, 56.2,
52.0, 49.9, 45.4, 35.0, 26.3, 26.1, 25.9, 24.9, 17.9, -4.0, -4.2; IR
Syntheses of Target Molecules 4 and 5. Iodine (564 mg, 2.22
mmol) was added to a mixture of aluminum (80 mg, 3 mmol) in
anhydrous benzene (4 mL). The mixture was refluxed for 0.5 h
and cooled to 10 °C, then n-Bu4N+I- (2 mg) and 16a (26 mg, 0.07
mmol) in benzene (2 mL) were added. The mixture were stirred
for 15 min at 10 °C and quenched with 2 M HCl at 0 °C. The
mixture wereas then extracted with EtOAc (3 × 20 mL). The
organic phase was washed with NaHCO3 solution and brine, dried
(Na2SO4), and concentrated in vacuo. The residue was purified by
column chromatography (hexanes/EtOAc, 2:1) to afford the target
(KBr) 3392, 2929, 2856, 1457, 1252, 1093, 1002, 834, 775 cm-1
;
HRMS m/z calcd for C25H44S2O3Si [M + Na]+ 507.2393 found
507.2388.
Syntheses of Macrolides 16a and 16b. The acid 15a (80 mg,
0.22 mmol) was dissolved in a mixture of trifluoroacetic acid (6
mL) and trifluoroacetic acid anhydride (1 mL) under Ar. The
solution was stirred over night at rt, poured into an excess of sodium
hydrogen carbonate, extracted with ether (3 × 5 mL), dried (Na2-
SO4), and concentrated in vacuo. The residue was purified by
column chromatography (hexanes/EtOAc, 5:1) to give the metabo-
lite 16a (32 mg, 42%) as a colorless oil: [R]25D -5 (c 1.1, CHCl3);
molecule 4 (16 mg, 68%) as a colorless oil: [R]25 -17 (c 1.0,
D
1
EtOH); H NMR (400 MHz, CDCl3) δ 6.29 (d, J ) 2.0 Hz, 1H),
6.22 (d, J ) 1.6 Hz, 1H), 4.92 (t, J ) 6.8 Hz, 1H), 3.89 (d, J )
15.6 Hz, 1H), 3.81 (d, J ) 3.6 Hz, 1H), 3.70 (dd, J ) 15.6 Hz, 6.8
Hz, 1H), 3.39 (d, J ) 12.0 Hz, 1H), 3.36 (s, 3H), 3.01 (dd, J )
14.8 Hz, 8.8 Hz, 1H), 1.53-1.62 (m, 6H), 1.19 (d, J ) 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 205.1, 172.2, 159.3, 158.3,
9848 J. Org. Chem., Vol. 72, No. 25, 2007

135.6, 119.6, 112.4, 102.7, 77.0, 73.9, 55.9, 48.8, 39.9, 32.6, 31.9,
20.9; IR (KBr) 3402, 2924, 1959, 1713, 1654, 1614, 1460, 1403,
1268, 1152, 1083, 1026, 848 cm-1; HRMS m/z calcd for C17H22O6
[M + H]+ 323.1489, found 323.1493.
1026, 846 cm-1; HRMS m/z calcd for C17H22O6 [M + Na]+
345.1309, found 345.1312.
Acknowledgment. We are grateful for the generous financial
support by the Special Doctorial Program Funds of the Ministry
of Education of China (20040730008), NSFC (QT program,
No.20572037), NCET-05-0879, the key grant project of the
Chinese ministry of Education (No.105169), and Gansu Science
Foundation (3ZS051-A25-004).
Target molecule 5 (19 mg, 70%) was obtained as a colorless oil
from 16b (30 mg, 0.086 mmol), iodine (326 mg, 1.28 mmol), and
aluminum (100 mg, 3.7 mmol) by the same operation for the
1
synthesis of 4: [R]25 -4 (c 0.3, EtOH); H NMR (300 MHz,
D
CDCl3) δ 8.98 (s, 1H), 6.94 (s, 1H), 6.34 (d, J ) 2.4 Hz, 1H), 5.97
(d, J ) 2.4 Hz, 1H), 5.13 (t, J ) 6.0 Hz, 1H), 3.95 (d, J ) 15.9
Hz, 1H), 3.78 (d, J ) 14.1 Hz, 1H), 3.59 (d, J ) 16.5 Hz, 1H),
3.33 (d, J ) 5.2 Hz, 1H), 3.25 (s, 3H), 3.13 (dd, J ) 14.1 Hz, 8.1
Hz, 1H), 1.55-1.87 (m, 6H), 1.25 (d, J ) 5.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 204.3, 172.0, 159.5, 159.4, 135.6, 118.3, 113.2,
102.7, 75.7, 72.3, 54.1, 49.2, 40.2, 31.2, 30.5, 18.8, 17.7; IR (KBr)
3402, 2923, 1959, 1712, 1655, 1614, 1461, 1403, 1269, 1153, 1083,
Supporting Information Available: Experimental procedures
and characterization data for compounds 7a and 7b, 10a/10b-16a/
16b, 4, and 5. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO701885N
J. Org. Chem, Vol. 72, No. 25, 2007 9849