Synthesis of schweinfurthin C, a geranylated stilbene from Macaranga schweinfurthii

Full text of DOI:10.1021/jo9908795

8718
J . Org. Chem. 1999, 64, 8718-8723
be based on directed ortho metalation.6,7 While com-
Syn th esis of Sch w ein fu r th in C,
a Ger a n yla ted Stilben e fr om
Ma ca r a n ga sch wein fu r th ii
mercial vanillin (7) is an attractive precursor to the “left
half” of schweinfurthin C, addition of the geranyl sub-
stituent to this aromatic compound is made somewhat
more difficult by the need for regiocontrolled elaboration
of the unsymmetrical starting material.
Edward M. Treadwell, Steven C. Cermak, and
David F. Wiemer*
Department of Chemistry, University of Iowa, Iowa City,
Iowa 52242-1294
Received J une 1, 1999
As part of a program investigating natural sources of
potential anticancer agents, Beutler et al. have studied
a cytotoxic extract of the plant Macaranga schweinfurthii
Pax from Cameroon.1 Application of a bioassay-guided
fractionation sequence to this extract yielded three novel
geranylated stilbenes, compounds that they named
schweinfurthins A-C (1-3). Our interests in isolation2
and synthesis3 of prenylated aromatic compounds led us
to undertake synthesis of these natural products, a task
that has grown more compelling because isolation of more
of the natural materials has not been straightforward.4
In this paper, we report the first total synthesis of
schweinfurthin C.
Our synthesis of the key “right half” intermediate
began with the commercial ester 8. After protection of
the phenolic groups by reaction with sodium hydride and
MOMCl,8 standard reduction of the protected ester 9 gave
benzyl alcohol 10.9 Reaction with TBSCl proceeded
smoothly to afford compound 11, but when the protected
ether 11 was treated with n-BuLi and geranyl bromide
(12), the aromatic alkylation product was not isolated.
Instead, an unexpected product (13) arising from benzylic
lithiation was obtained in modest yield (21%).6d,10 When
metalation was conducted with n-BuLi and TMEDA,
reaction with geranyl bromide gave a mixture of com-
pounds 13 and 14 in low yield. However, when metalation
was carried out with n-BuLi, TMEDA, and CuCN,9
presumably forming an intermediate cuprate, subsequent
reaction with geranyl bromide gave a single product
isomeric to compound 13. The symmetry of that product
was evident in its spectral data, allowing unambiguous
identification of the desired phenol derivative 14. After
cleavage of the silyl group by reaction with TBAF to
obtain alcohol 15, formation of the mesylate (16) and
displacement with NaI gave benzylic iodide 17. A final
Synthesis of stilbenes is readily accomplished through
Wittig-type assembly of the central olefin.5 Because
schweinfurthin C is not quite symmetrical, application
of such an approach to this synthesis would require
preparation of two geranylated phenols bearing different
substitution patterns (4 and 5). In terms of retrosynthetic
analysis, the “right half” of schweinfurthin C can be
readily traced to a resorcinol derivative such as com-
pound 6, and assembly of the key intermediate 5 could
(6) (a) Winkle, M. R.; Ronald, R. C. J . Org. Chem. 1982, 47, 2101-
2108. (b) Napolitano, E.; Giannone, E.; Fiaschi, R.; Marsili, A. J . Org.
Chem. 1983, 48, 3653-3657. (c) Sneickus, V. Chem. Rev. 1990, 90,
879-933. (d) Thayumanavan, S.; Basu, A.; Beak, P. J . Am. Chem. Soc.
1997, 119, 8209-8216.
(7) Gschwend, H. W.; Rodiguez, H. R. Org. React. 1979, 26, 1-360.
(8) Townsend, C. A.; Davis, S. G.; Christensen, S. B.; Link, J . C.;
Lewis, C. P. J . Am. Chem. Soc. 1981, 103, 6885-6888.
(9) Falck, J . R.; Reddy, K. K.; Chandrasekhar, S. Tetrahedron Lett.
1997, 38, 5245-5248.
(10) (a) Harris, T. D.; Roth, G. P. J . Org. Chem. 1979, 44, 2004-
2007. (b) Court, J . J .; Hlasta, D. J . Tetrahedron Lett. 1996, 37, 1335-
1338. (c) Ludt, R. E.; Crowther, G. P.; Hauser, C. R. J . Org. Chem.
1970, 35, 1288-1296.
(1) Beutler, J . A.; Shoemaker, R. H.; J ohnson, T.; Boyd, M. R. J .
Nat. Prod. 1998, 61, 1509-1512.
(2) (a) Ampofo, S. A.; Roussis, V.; Wiemer, D. F. Phytochemistry
1987, 26, 2367-2370. (b) Green, T. P.; Treadwell, E. M.; Wiemer, D.
F. J . Nat. Prod. 1999, 62, 367-368.
(3) Blunt, S. B.; Chen, T. B.; Wiemer, D. F. J . Nat. Prod. 1998, 61,
1400-1403.
(11) (a) Bates, R. W.; Gabel, C. J . Tetrahedron Lett. 1993, 34, 3547-
3550. (b) Manners, G. D.; Wong, R. Y. J . Chem. Soc., Perk. Trans. 1
1981, 1849-1854. (c) Daves, G. D., J r.; Moore, H. W.; Schwab, D. E.;
Olsen, R. K.; Wilczynski, J . J .; Folkers, K. J . Org. Chem. 1967, 32,
1414-1417. (d) Yamada, S.; Ono, F.; Katagiri, T.; Tanaka, J . Synth.
Commun. 1975, 5, 181-184.
(4) Beutler, J . A. Personal communication, 1999.
(5) (a) Bachelor, F. W.; Loman, A. A.; Snowdon, L. R. Can. J . Chem.
1970, 48, 1554-1557. (b) Moody, C. J .; Warrellow, G. J . J . Chem. Soc.,
Perk. Trans. 1 1990, 2929-2936. (c) Cushman, M.; Nagarathnam, D.;
Gopal, D.; Chakraborti, A. K.; Lin, C. M.; Hamel, E. J . Med. Chem.
1991, 34, 2579-2588.
(12) Asakawa, Y.; Kondo, K.; Tori, M.; Hashimoto, T.; Ogawa, S.
Phytochemistry 1991, 30, 219-234.
10.1021/jo9908795 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/12/1999

Notes
J . Org. Chem., Vol. 64, No. 23, 1999 8719
Arbuzov reaction with (EtO)3P gave the desired phos-
phonate 18.
the starting material is at least theoretically possible,
these results encouraged examination of a similar strat-
egy with phosphonate 18.
A priori, compound 18 could be used to prepare
schweinfurthin C through either a linear strategy based
on condensation with a minimally substituted aldehyde
or via a convergent approach where an intact “right half”
was employed in stilbene formation. Despite the attrac-
tion of a convergent sequence in terms of cumulative
yield, a linear sequence appeared to offer some advan-
tages in terms of the minimal number of protection steps
required and the opportunities for regiocontrol. In par-
ticular, C-alkylation of a vanillin derivative through
reaction with an allylic halide would be expected11,12 to
afford only the ortho alkylation product, while a directed
ortho metalation strategy would have to contend with at
least two potential directing groups. Thus, a linear
approach based on initial assembly of the stilbene and
subsequent addition of the geranyl chain was investi-
gated in a model system.
Condensation of aldehyde 19 with phosphonate 18 gave
a mixture of stilbene products with (25) and without (26)
the silyl group, and complete conversion to the phenol
26 was brought about by treatment of compound 25 with
TBAF. Despite the successful transformation observed
with the model compound 22, reaction of phenol 26 with
sodium metal and geranyl bromide proved problematic.
While traces of the desired C-alkylated product 27 were
observed, in the best case only 14% of this product was
isolated. Instead, the major product of this reaction was
the O-alkylated isomer (28) and little starting material
was recovered. Thus, we were pressed to explore an
alternate sequence for preparation of schweinfurthin C.
To pursue a more convergent approach to this natural
product, to allow regiocontrolled introduction of the
geranyl chain, and to simplify the eventual deprotection
of the phenols, we chose to begin this sequence with the
known aldehyde 29,14 which is readily prepared from
vanillin.15 After reduction with LiAlH4 and reaction of
the resulting alcohol (30) with TESCl to obtain the silyl
ether 31, halogen-metal exchange16 was attempted.
Upon treatment with n-BuLi followed by geranyl bro-
mide, the desired C-alkylated product 32 was obtained
in 54% yield. Cleavage of the silyl ether gave alcohol 33,
For construction of the model stilbene, vanillin (7) was
first treated with TBSCl to obtain the protected aldehyde
19.13 Condensation of this aldehyde with phosphonate 20
gave the protected stilbene 21 along with some of the
phenol 22, and subsequent reaction with TBAF com-
pleted formation of the phenol. Reaction of phenol 22 with
sodium metal and geranyl bromide gave the C-alkylated
product 23 in 42% yield, along with ∼46% of recovered
starting material. The O-alkylated product 24 was oc-
casionally observed as a minor byproduct, but it was
readily identified by the relatively downfield resonances
of both C-1 in the 13C NMR spectrum and the C-1
(14) Stafford, J . A.; Valvano, N. L. J . Org. Chem. 1994, 59, 4346-
4349.
(15) (a) Manchand, P. S.; Belica, P. S.; Wong, H. S. Synth. Commun.
1990, 20, 2659-2666. (b) Lange, R. G. J . Org. Chem. 1962, 27, 2037-
2039.
(16) (a) J ones, R. G.; Gilman, H. Org. React. 1951, 6, 339-366. (b)
Tanaka, H.; Hiroo, M.; Ichino, K.; Ito, K. Chem. Pharm. Bull. 1989,
37, 1441-1445.
1
hydrogens in the H NMR spectrum. Because recycling
(13) Singh, S. B.; Pettit, G. R. Synth. Commun. 1987, 17, 877-892.

8720 J . Org. Chem., Vol. 64, No. 23, 1999
Notes
generally modest yields. However, the material prepared
in this manner proved identical to the natural material
in direct TLC comparisons with an authentic sample as
well as in comparison of 1H and 13C NMR data with
literature values.1 Thus, the first synthesis of this natural
product is now complete.
Schweinfurthin C is clearly the least complicated
example of this small family of natural products, and in
contrast to schweinfurthins A and B, it did not demon-
strate significant anticancer activity in the NCI screens.
Nevertheless, this synthesis of schweinfurthin C estab-
lishes strategies that can be applied in syntheses of the
more complex members of this family and provides an
intermediate in phosphonate 18 that would be useful for
preparation of either schweinfurthin A or B. Our efforts
to extend this work to allow preparation of related
natural products and to identify the molecular targets
for the cytotoxic geranylated stilbenes will be reported
in due course.
Exp er im en ta l Section
Tetrahydrofuran (THF) and diethyl ether were distilled from
sodium/benzophenone immediately prior to use, DMF was
distilled from molecular sieves, and CH2Cl2 and Et3N were
distilled from CaH. All nonaqueous reactions were conducted
in oven-dried or flame-dried glassware, under an atmosphere
of argon or nitrogen, with magnetic stirring. Oil-free NaH was
prepared by washing mineral oil dispersions five times with an
equal volume of pentane. Flash chromatography was carried out
on silica gel with 40 µm average particle diameter. NMR spectra
were recorded at 300 MHz for 1H with CDCl3 as solvent and
and oxidation with PDC to the aromatic aldehyde 34
provided the key “left half” intermediate for this ap-
proach.
(CH3)4Si (1H) or CDCl3 13C, 77.0 ppm) as internal standards
(
unless otherwise noted. 31P NMR chemical shifts are reported
in ppm relative to 85% H3PO4 (external standard). Low-resolu-
tion (70 eV), high-resolution, and FAB mass spectra were
obtained at the University of Iowa Mass Spectrometry Facility.
Elemental analyses were performed by Atlantic Microlab, Inc.
(Norcross, GA).
t er t -Bu t yl[(3,5-b is(m e t h oxym e t h oxy)b e n zyl)oxy]d i-
m eth ylsila n e (11). To a solution of alcohol 109 (2.74 g, 12.0
mmol) in CH2Cl2 (50 mL) at 0 °C were added TBSCl (2.80 g,
18.6 mmol) and imidazole (3.32 g, 48.8 mmol), and the reaction
was stirred for 12 h. The resulting solution was quenched by
addition of H2O and EtOAc. After the aqueous layer was
extracted with EtOAc, the combined organic layers were dried
(MgSO4), filtered, and concentrated in vacuo to afford compound
11 (3.77 g, 92%) as a clear oil. An analytical sample was prepared
by flash column chromatography (9:1 hexanes/EtOAc): 1H NMR
δ 6.68 (d, J ) 2.4 Hz, 2H), 6.61 (t, J ) 2.4 Hz, 1H), 5.14 (s, 4H),
4.68 (s, 2H), 3.46 (s, 6H), 0.95 (s, 9H), 0.10 (s, 6H); 13C NMR δ
158.2 (2C), 144.1, 107.1 (2C), 103.3, 94.4 (2C), 64.6, 55.8 (2C),
25.9 (3C), 18.3, -5.4 (2C); EIMS m/z (relative intensity) 342 (M+,
1), 285 (15), 223 (19), 89 (100). Anal. Calcd for C17H30O5Si: C,
59.62; H, 8.83. Found: C, 59.84; H, 9.01.
(3E)-1-ter t-Bu t yld im et h ylsilyloxy-4,8-d im et h yl-1-(3,5-
bis(m eth oxym eth oxy)p h en yl)-3,7-n on a d ien e (13). To a so-
lution of protected alcohol 11 (1.02 g, 2.97 mmol) in THF (30
mL) at 0 °C was added n-BuLi (1.31 mL, 2.50 M in hexane, 3.27
mmol) dropwise over 15 min. After 3 h, the solution was cooled
to -78 °C, and geranyl bromide (0.59 mL, 3.0 mmol) was added.
The reaction was stirred for 1 h and then allowed to warm to
room temperature over 30 min and stirred for 30 min. The
resulting solution was quenched by addition of H2O and stirred
for 1 h. This mixture was extracted with EtOAc, and the
combined organic extracts were dried (Na2SO4), filtered, and
concentrated in vacuo. The resulting solid was purified by flash
column chromatography (9:1 hexanes/EtOAc) to afford compound
13 (298 mg, 21%) as a yellow oil: 1H NMR δ 6.67 (d, J ) 3.9 Hz,
2H), 6.58 (t, J ) 3.9 Hz, 1H), 5.21-5.07 (m, 2H), 5.14 (s, 4H),
4.56 (s, 1H), 3.47 (s, 6H), 2.42-2.24 (m, 2H), 2.09-1.93 (m, 4H),
1.68 (s, 3H), 1.60 (s, 3H), 1.54 (s, 3H), 0.88 (s, 9H), 0.02 (s, 3H),
-0.09 (s, 3H); 13C NMR δ 157.9 (2C), 148.5, 136.9, 131.3, 124.4,
Condensation of aldehyde 34 and phosphonate 18 gave
the desired stilbene 35 as a single olefin isomer. Depro-
tection of compound 35 was accomplished by hydrolysis
in 3 M HCl in methanol in ∼50% yield. Given that this
final deprotection required hydrolysis of four MOM
groups, it may not be surprising that this reaction gave

Notes
J . Org. Chem., Vol. 64, No. 23, 1999 8721
120.6, 107.3 (2C), 103.2, 94.5 (2C), 75.1, 55.9 (2C), 39.8, 39.5,
26.7, 25.8 (3C), 25.6, 18.2, 17.6, 16.3, -4.7, -5.0; EIMS m/z
(relative intensity) 478 (M+, 4), 355 (100), 69 (98); HRMS calcd
for C27H46O5Si 478.3116, found 478.3115.
17 (501 mg, 1.06 mmol) in triethyl phosphite (5.0 mL) was heated
at reflux for 2.5 h. The solution was allowed to cool to room
temperature and placed on a high vacuum line to remove the
excess triethyl phosphite. The resulting yellow oil was purified
by flash column chromatography (9:1 EtOAc/hexanes) to afford
phosphonate 18 (511 mg, 100%) as a yellow oil: 1H NMR δ 6.71
(d, J ) 1.8 Hz, 2H), 5.17 (s, 4H), 5.21-5.16 (m, 1H), 5.08-5.04
(tm, J ) 6.6 Hz, 1H), 4.04 (dq, J ) 6.9, 6.9 Hz, 4H), 3.45 (s, 6H),
3.37 (d, J ) 6.9 Hz, 2H), 3.08 (d, J PH ) 21.3 Hz, 2H), 2.05-2.00
(m, 2H), 1.97-1.93 (m, 2H), 1.77 (s, 3H), 1.64 (s, 3H), 1.56 (s,
3H), 1.27 (t, J ) 6.9 Hz, 6H); 13C NMR δ 155.3 (d, J CP ) 3.1 Hz,
ter t-Bu t yl[(4-(2E-3,7-d im et h yl-2,6-oct a d ien yl)-3,5-b is-
(m eth oxym eth oxy)ben zyl)oxy]d im eth ylsila n e (14). To a
solution of protected alcohol 11 (1.42 g, 4.15 mmol) and TMEDA
(1.30 mL, 8.6 mmol) in THF (15 mL) at -20 °C was added
n-BuLi (2.20 mL, 2.15 M in hexane, 4.73 mmol) dropwise over
10 min. After 50 min, CuCN (379 mg, 4.23 mmol) was added as
a solid in one portion. After another 50 min at -20 °C, the
solution was added via cannula into a solution of geranyl
bromide (0.82 mL, 4.1 mmol) in THF (15 mL), which was cooled
to -78 °C. After 2 h at -78 °C, the reaction mixture was allowed
to warm to room temperature followed by the addition of H2O
and the resulting solution stirred for 45 min. The resulting blue/
green solution was extracted with EtOAc, and the combined
organic extracts were dried (MgSO4), filtered, and concentrated
in vacuo. The resulting oil was purified by flash column
chromatography (95:5 hexanes/EtOAc) to afford compound 14
(1.46 g, 73%) as a yellow oil: 1H NMR δ 6.77 (s, 2H), 5.24-5.18
(tm, J ) 7.2 Hz, 1H), 5.17 (s, 4H), 5.09-5.04 (tm, J ) 6.8 Hz,
1H), 4.69 (s, 2H), 3.46 (s, 6H), 3.39 (d, J ) 6.9 Hz, 2H), 2.08-
2.01 (m, 2H), 1.98-1.93 (m, 2H), 1.78 (s, 3H), 1.64 (s, 3H), 1.57
(s, 3H), 0.95 (s, 9H), 0.10 (s, 6H); 13C NMR δ 155.6 (2C), 140.6,
134.3, 131.1, 124.4, 122.9, 118.6, 105.7 (2C), 94.5 (2C), 64.9, 55.8
(2C), 39.8, 26.7, 25.9 (3C), 25.6, 22.5, 18.3, 17.6, 16.0, -5.3 (2C);
EIMS, m/z (relative intensity) 478 (M+, 2), 355 (48), 69 (94), 45
(100); HRMS calcd for C27H46O5Si 478.3116, found 478.3110.
Anal. Calcd for C27H46O5Si: C, 67.74; H, 9.68. Found: C, 67.48;
H, 9.77.
4-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-3,5-b is(m et h oxy-
m eth oxy)ben zyl Alcoh ol (15). To a solution of protected
alcohol 14 (473 mg, 0.99 mmol) in THF (20 mL) was added
dropwise TBAF (1.0 mL, 1.0 M in THF, 1.0 mmol), and the
reaction mixture was stirred at room temperature for 3 h. The
resulting solution was quenched by addition of H2O and EtOAc.
The aqueous layer was extracted with EtOAc, and the combined
organic layers were dried (Na2SO4), filtered, and concentrated
in vacuo. The resulting liquid was purified by flash column
chromatography (4:1 hexanes/EtOAc) to afford compound 15 (310
mg, 86%) as a clear oil: 1H NMR δ 6.76 (s, 2H), 5.22-5.17 (tm,
J ) 7.3 Hz, 1H), 5.17 (s, 4H), 5.08-5.03 (tm, J ) 6.7 Hz, 1H),
4.58 (s, 2H), 3.45 (s, 6H), 3.38 (d, J ) 6.9 Hz, 2H), 2.51 (br s,
1H), 2.07-2.00 (m, 2H), 1.96-1.92 (m, 2H), 1.78 (s, 3H), 1.64
(s, 3H), 1.56 (s, 3H); 13C NMR δ 155.6 (2C), 140.1, 134.5, 131.1,
124.3, 122.6, 119.2, 106.3 (2C), 94.2 (2C), 65.1, 55.9 (2C), 39.7,
26.6, 25.5, 22.4, 17.5, 16.0; EIMS m/z (relative intensity) 364
(M+, 4), 241 (100), 233 (63), 69 (69); HRMS calcd for C21H32O5
364.2251, found 364.2250. Anal. Calcd for C21H32O5: C, 69.20;
H, 8.85. Found: C, 69.08; H, 8.86.
4-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-3,5-b is(m et h oxy-
m eth oxy)ben zyl Iod id e (17). To a solution of alcohol 15 (837
mg, 2.3 mmol) and Et3N (0.42 mL, 3.0 mmol) in CH2Cl2 (60 mL)
at 0 °C was added methanesulfonyl chloride (0.23 mL, 3.0 mmol)
dropwise. After the reaction mixture was stirred at 0 °C for 1 h,
it was extracted sequentially with H2O, saturated NaHCO3, and
brine. The organic layer was dried (Na2SO4), filtered, and
concentrated in vacuo. The yellow residue was dissolved in
acetone (40 mL), and solid NaI (1.04 g, 6.91 mmol) was added
in one portion. The solution was stirred at room temperature
for 22 h as a precipitate formed. The resulting orange solution
was added to a solution of saturated NaHCO3 and extracted with
EtOAc. The combined organic layers were then washed with
brine, dried (MgSO4), filtered, and concentrated in vacuo. The
resulting brown oil was purified by flash column chromatography
(9:1 hexanes/EtOAc) to afford iodide 17 (937 mg, 86%) as a yellow
oil: 1H NMR δ 6.79 (s, 2H), 5.20-5.16 (tm, J ) 7.3 Hz, 1H),
5.17 (s, 4H), 5.08-5.03 (tm, J ) 6.9 Hz, 1H), 4.39 (s, 2H), 3.46
(s, 6H), 3.35 (d, J ) 6.9 Hz, 2H), 2.08-2.00 (m, 2H), 1.97-1.92
(m, 2H), 1.77 (s, 3H), 1.63 (s, 3H), 1.56 (s, 3H); 13C NMR δ 155.5
(2C), 137.8, 134.6, 131.1, 124.2, 122.2, 120.0, 108.3 (2C), 94.3
(2C), 55.9 (2C), 39.7, 26.6, 25.6, 22.5, 17.5, 16.0, 6.4; EIMS, m/z
(relative intensity) 347 (M+ - 127, 46), 69 (81), 46 (100); HRMS
calcd for C21H31O4 (M+ - I) 347.2223, found 347.2241.
2C), 134.1, 130.8, 130.0 (d, J CP ) 8.6 Hz), 124.1, 122.5 (d, J CP
)
1.8 Hz), 118.5, 109.3 (d, J CP ) 3.0 Hz, 2C), 94.1 (2C), 61.7 (d,
J CP ) 6.7 Hz, 2C), 55.6 (2C), 39.5, 33.5 (d, J CP ) 137.3 Hz), 26.4,
25.3, 22.2, 17.3, 16.0 (d, J CP ) 6.1 Hz, 2C), 15.7; 31P NMR δ 26.8;
EIMS, m/z (relative intensity) 483 (M+ - 1, 2), 46 (100); HRMS
calcd for C25H41O7P 484.2591, found 484.2607.
4-(t er t -B u t y ld im e t h ylsily lo x y )-3-m e t h o xy b e n za ld e -
h yd e (19).13 Diisopropylethylamine (2.15 mL, 12.3 mmol) was
added to a solution of vanillin (1.25 g, 8.24 mmol) in DMF (15
mL) at 0 °C, followed by the addition of TBSCl (1.37 g, 9.10
mmol). After the solution was stirred for 130 min, ice-cold H2O
was added, followed by Et2O and saturated NaHCO3. The
resulting layers were separated, and the organic phase was
washed with H2O, saturated NaHCO3, and H2O. The organic
phase was dried (MgSO4) and concentrated in vacuo to yield a
clear oil (1.99 g, 91%). The 1H and 13C NMR and the mass
spectrum matched literature values.13,17
ter t-Bu tyld im eth ylsilyloxy-2-m eth oxy-4-((E)-p h en yleth -
en yl)ben zen e (21). NaH (458 mg, 19.1 mmol) was added in
portions to diethylbenzyl phosphonate (1.71 g, 7.49 mmol) in
THF (60 mL) at 0 °C, and the solution was stirred for 30 min.
Aldehyde 19 (1.98 g, 7.43 mmol) in THF (15 mL) was then added
dropwise and the reaction stirred overnight. The reaction was
quenched by addition of H2O, and the aqueous layer was
extracted with EtOAc. The combined organic layers were washed
with brine, dried (MgSO4), and concentrated in vacuo. Purifica-
tion by flash column chromatography (10:1 hexanes/EtOAc)
afforded the silylated stilbene 21 (628 mg, 25%) along with
phenol 22 (594 mg, 33%). For compound 21: clear oil; 1H NMR
δ 7.48-7.43 (m, 2H), 7.35-7.27 (m, 2H), 7.23-7.17 (m, 1H), 7.02
(d, J ) 16.2 Hz, 1H), 7.00 (d, J ) 1.6 Hz, 1H), 6.96 (dd, J ) 8.1,
1.9 Hz, 1H), 6.93 (d, J ) 16.3 Hz, 1H), 6.82 (d, J ) 8.1 Hz, 1H),
3.82 (s, 3H), 1.01 (s, 9H), 0.17 (s, 6H); 13C NMR δ 151.0, 145.0,
137.5, 131.2, 128.6, 128.5 (2C), 127.1, 126.7, 126.2 (2C), 120.9,
119.7, 109.7, 55.3, 25.7 (3C), 18.4, -4.7 (2C); EIMS, m/z (relative
intensity) 340 (M+, 6), 325 (1), 283 (37), 268 (100). Anal. Calcd
for C21H28O2Si: C, 74.07; H, 8.29. Found: C, 73.81; H, 8.32.
For compound 22: white solid; mp 131-132 °C; 1H NMR δ
7.48-7.43 (m, 2H), 7.35-7.29 (m, 2H), 7.24-7.17 (m, 1H), 7.03
(d, J ) 16.6 Hz, 1H), 7.01 (d, J ) 1.8 Hz, 1H), 7.01 (dd, J ) 8.3,
2.1 Hz, 1H), 6.93 (d, J ) 16.2 Hz, 1H), 6.90 (d, J ) 8.7 Hz, 1H),
5.73 (br s, 1H), 3.87 (s, 3H); 13C NMR δ 146.7, 145.5, 137.5, 129.9,
128.6 (2C), 128.5, 127.2, 126.4, 126.2 (2C), 120.4, 114.5, 108.2,
55.9; EIMS, m/z (relative intensity) 226 (M+, 100), 211 (4), 165
(44).
2-Meth oxy-4-((E)-p h en yleth en yl)p h en ol (22). TBAF (3.1
mL, 1.0 M in THF, 3.1 mmol) was added to a solution of silane
21 (780 mg, 2.29 mmol) in Et2O (10 mL) at 0 °C. After the
solution was stirred for 20 min, the reaction was quenched by
addition of saturated NH4Cl, followed by H2O. The aqueous layer
was extracted with EtOAc, and the organic extract was dried
(MgSO4) and concentrated in vacuo to yield compound 22 as a
white solid (620 mg, 80%) identical with material obtained above.
An analytical sample was prepared by purification by flash
column chromatography (6:1 hexanes/EtOAc). Anal. Calcd for
C15H14O2: C, 79.62; H, 6.24. Found: C, 79.20; H, 6.20.
6-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-2-m et h oxy-4-((E)-
p h en yleth en yl)p h en ol (23). Small slices of metallic sodium
(130 mg, 5.65 mmol) were added to stilbene 22 (309 mg, 1.37
mmol) in Et2O (35 mL), and the resulting mixture was stirred
at room temperature for 2 h. Geranyl bromide (0.5 mL, 2.5 mmol)
was then added, and the solution was heated at reflux for
Dieth yl (4-((2E)-3,7-Dim eth yl-2,6-octadien yl)-3,5-bis(m eth -
oxym eth oxy)ben zyl)p h osp h on a te (18). A solution of iodide
(17) Barclay, L. R. C.; Cromwell, G. R.; Hilborn, J . W. Can. J . Chem.
1994, 72, 35-41.

8722 J . Org. Chem., Vol. 64, No. 23, 1999
Notes
approximately 45 h. After the reaction had cooled to room
temperature, it was quenched by addition of H2O, and the
aqueous layer was extracted with EtOAc. The combined organic
extracts were washed with brine, dried (MgSO4), and concen-
trated in vacuo. Purification by flash column chromatography
(10:1 hexanes/EtOAc) afforded the alkylated stilbene 23 (152 mg,
42%) as a yellow oil along with some recovered starting material
(135 mg, 44%): 1H NMR δ 7.50-7.44 (m, 2H), 7.35-7.29 (m,
2H), 7.24-7.17 (m, 1H), 7.02 (d, J ) 16.3 Hz, 1H), 6.91 (d, J )
16.2 Hz, 1H), 6.90 (br s, 2H), 5.80 (s, 1H), 5.40-5.33 (tm, J )
7.2 Hz, 1H), 5.16-5.09 (tm, J ) 6.8 Hz, 1H), 3.87 (s, 3H), 3.38
(d, J ) 7.3 Hz, 2H), 2.13-2.03 (m, 2H), 2.03-1.95 (m, 2H), 1.74
(s, 3H), 1.67 (s, 3H), 1.59 (s, 3H); 13C NMR δ 146.4, 143.3, 137.6,
136.3, 131.3, 128.9, 128.9, 128.5 (2C), 127.4, 127.0, 126.1 (2C),
126.0, 124.2, 122.0, 121.1, 105.7, 55.9, 39.7, 27.9, 26.6, 25.6, 17.5,
16.1; EIMS, m/z (relative intensity) 362 (M+, 14), 279 (100), 226
(30), 137 (70), 91 (58). Anal. Calcd for C25H30O2: C, 82.82; H,
8.34. Found: C, 82.62; H, 8.37.
ter t-Bu t yld im et h ylsilyloxy-4-((E)-4-((2E)-3,7-d im et h yl-
2,6-octa d ien yl)-3,5-bis(m eth oxym eth oxy)p h en yleth en yl)-
2-m eth oxyben zen e (25). NaH (28 mg, 1.2 mmol) was added
to phosphonate 18 (257 mg, 0.53 mmol) in THF (20 mL) at 0 °C,
the ice bath was removed, and the reaction was stirred for 45
min. Aldehyde 19 (154 mg, 0.58 mmol) in THF (2.5 mL) was
then added dropwise and the reaction stirred for 10 h. The
reaction was quenched by addition of H2O and the aqueous phase
extracted with EtOAc. The combined organic phases were
washed with brine, dried (MgSO4), and concentrated in vacuo.
Purification by flash column chromatography (10:1 hexanes/
EtOAc) afforded the silylated stilbene 25 (127 mg, 40%), along
with the corresponding phenol 26 (44 mg, 17%). For stilbene
25: 1H NMR δ 7.05 (d, J ) 1.7 Hz, 1H), 7.01 (d, J ) 16.3 Hz,
1H), 6.99 (dd, J ) 8.1, 1.7 Hz, 1H), 6.96 (s, 2H), 6.93 (d, J )
16.9 Hz, 1H), 6.85 (d, J ) 8.1 Hz, 1H), 5.26 (s, 4H), 5.26 (m,
1H), 5.10 (tm, J ) 6.4 Hz, 1H), 3.89 (s, 3H), 3.53 (s, 6H), 3.43
(d, J ) 7.0 Hz, 2H), 2.10-2.03 (m, 2H), 2.03-1.95 (m, 2H), 1.82
(s, 3H), 1.67 (s, 3H), 1.60 (s, 3H), 1.04 (s, 9H), 0.20 (s, 6H); 13C
NMR δ 155.9 (2C), 151.0, 144.9, 136.6, 134.6, 131.3, 131.2, 128.2,
126.9, 124.4, 122.6, 120.9, 119.7, 119.5, 109.6, 106.0 (2C), 94.5
(2C), 55.9 (2C), 55.4, 39.8, 26.7, 25.68 (3C), 25.63, 22.7, 18.4,
17.6, 16.0, -4.7 (2C); EIMS, m/z (relative intensity) 596 (M+,
22), 595 (50), 539 (9), 46 (100).
unreacted starting material (17 mg, 40%). For compound 27:
yellow oil; H NMR (CD3OD as solvent and internal reference)
1
δ 6.98 (br s, 1H), 6.95 (d, J ) 16.2 Hz, 1H), 6.90 (s, 2H), 6.84 (d,
J ) 16.0 Hz, 1H), 6.83 (br s, 1H), 5.34-5.30 (m, 1H), 5.30-5.04
(m, 3H), 5.22 (s, 4H), 4.85 (s, 6H), 3.89 (s, 3H), 3.36 (d, J ) 7.0
Hz, 2H), 3.30 (d, J ) 7.0 Hz, 2H), 2.20-2.00 (m, 6H), 2.00-1.90
(m, 2H), 1.77 (s, 3H), 1.72 (s, 3H), 1.64 (s, 3H), 1.60 (s, 3H), 1.58
(s, 3H), 1.54 (s, 3H); 13C NMR (CD3OD as solvent and internal
reference) δ 161.9, 157.1, 148.8, 145.3, 138.3, 136.7, 135.2, 132.2,
132.1, 129.91, 129.88, 129.1, 126.8, 125.4 (2C), 124.3, 124.0,
121.9, 120.3, 107.5, 106.9 (2C), 95.7 (2C), 56.4, 56.3 (2C), 40.9
(2C), 28.9, 27.7 (2C), 26.0, 25.8, 23.4, 17.8, 17.7, 16.3, 16.2.
For the O-alkylated product 28: yellow oil; 1H NMR δ 7.02
(d, J ) 1.5 Hz, 1H), 7.01 (dd, J ) 8.6, 1.5 Hz, 1H), 6.99 (d, J )
16.3 Hz, 1H), 6.94 (d, J ) 16.0 Hz, 1H), 6.93 (s, 2H), 6.85 (d, J
) 8.3 Hz, 1H), 5.52 (tm, J ) 6.5 Hz, 1H), 5.24 (s, 4H), 5.24 (m,
1H), 5.07 (tm, J ) 6.5 Hz, 2H), 4.63 (d, J ) 6.5 Hz, 2H), 3.93 (s,
3H), 3.50 (s, 6H), 3.40 (d, J ) 7.0 Hz, 2H), 2.18-1.90 (m, 8H),
1.79 (s, 3H), 1.73 (s, 3H), 1.67 (s, 3H), 1.64 (s, 3H), 1.60 (s, 3H),
1.57 (s, 3H); 13C NMR δ 155.8 (2C), 149.5, 148.0, 140.5, 136.5,
134.5, 131.6, 131.1, 130.3, 128.0, 126.7, 124.3, 128.8, 122.6, 119.7,
119.6, 119.5, 113.0, 108.8, 105.9 (2C), 94.4 (2C), 65.8, 55.9 (2C),
55.8, 39.7, 39.5, 26.6, 26.2, 25.6 (2C), 22.6, 17.6, 17.5, 16.6, 16.0;
HR FAB-MS calcd for C39H54O6 618.3922, found 618.3902.
5-Br om o-3,4-bis(m eth oxym eth yoxy)ben za ld eh yd e (29).14
To a solution of 5-bromo-3,4-dihydroxybenzaldehyde15b (1.85 g,
8.51 mmol) in DMF (15 mL) at 0 °C was added diisopropyleth-
ylamine (3.6 mL, 38 mmol) followed by MOMCl (1.80 mL, 23.7
mmol), and the solution was stirred for 28 h while it warmed to
room temperature. The reaction was quenched by addition of
H2O and saturated NaHCO3. Ether was added, the layers were
separated, and the organic phase was washed with H2O,
saturated NaHCO3, and brine. After the organic phase was dried
(MgSO4) and concentrated in vacuo, compound 29 was obtained
as a clear oil (1.79 g, 69%). Both 1H and 13C NMR data were in
agreement with literature values.14
5-Br om o-3,4-bis(m eth oxym eth oxy)ben zyl a lcoh ol (30).
Aldehyde 29 (810 mg, 2.65 mmol) in Et2O (15 mL) was added
dropwise to a suspension of LiAlH4 (69.5 mg, 1.83 mmol) in Et2O
(60 mL) at 0 °C, and the remaining aldehyde was transferred
with additional Et2O (4 mL). After the reaction mixture was
stirred for 10 min, it was quenched by addition of EtOAc,
followed by H2O, 0.5 M NaOH, and H2O. The aqueous phase
was extracted with EtOAc, and the combined organic phases
were dried (MgSO4) and concentrated in vacuo. Purification of
the resulting oil by flash column chromatography (2:1 hexanes/
EtOAc) afforded compound 30 (619 mg, 76%) as a clear oil: 1H
NMR δ 7.20 (br s, 1H), 7.07 (br s, 1H), 5.18 (s, 2H), 5.16 (s, 2H),
4.56 (s, 2H), 3.65 (s, 3H), 3.48 (s, 3H), 2.54 (br s, 1H); 13C NMR
δ 150.8, 143.1, 138.5, 124.4, 117.7, 114.0, 98.7, 95.1, 63.9, 57.8,
56.3; EIMS, m/z (relative intensity) 308 (M++2, 14), 306 (M+,
14), 246 (5), 244 (5), 230 (100). Anal. Calcd for C11H15BrO5: C,
43.16; H, 4.94. Found: C, 42.76; H, 4.84.
[5-Br om o-3,4-b is(m e t h oxym e t h oxy)b e n zyl]t r ie t h yl-
sila n e (31). TESCl (1.60 mL, 9.41 mmol) was added to alcohol
30 (1.14 g, 3.71 mmol) in CH2Cl2 (25 mL) at 0 °C, followed by
imidazole (1.04 mg, 15.2 mmol). After the mixture was stirred
for 22 h, H2O and EtOAc were added. The aqueous phase was
extracted with EtOAc, and the combined organic layers were
washed with brine, dried (MgSO4), and concentrated in vacuo.
Purification by flash chromatography (6:1 hexanes/EtOAc) gave
compound 31 as a clear oil (1.44 g, 99%): 1H NMR δ 7.18 (d, J
) 1.2 Hz, 1H), 7.09 (d, J ) 1.3 Hz, 1H), 5.18 (s, 2H), 5.16 (s,
2H), 4.64 (s, 2H), 3.65 (s, 3H), 3.48 (s, 3H), 0.98 (t, J ) 7.9 Hz,
9H), 0.65 (q, J ) 7.9 Hz, 6H); 13C NMR δ 150.7, 142.7, 138.7,
123.6, 117.4, 113.5, 98.7, 95.1, 63.5, 57.7, 56.0, 6.6 (3C), 4.3 (3C);
EIMS, m/z (relative intensity) 422 (M+ + 2, 5), 420 (M+, 4), 215
(100), 213 (99), 117 (50). Anal. Calcd for C17H29BrO5Si: C, 48.57;
H, 6.95. Found: C, 48.40; H, 6.90.
[5-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-3,4-b is(m et h oxy-
m eth oxy)ben zyl]tr ieth ylsila n e (32). A solution of silane 31
(177 mg, 0.42 mmol) in Et2O (10 mL) was treated with n-BuLi
(0.20 mL, 2.47 M in hexanes, 0.45 mmol) at -78 °C. After the
solution was stirred for 20 min, geranyl bromide (0.25 mL, 1.3
mmol) was added dropwise, and the reaction was allowed to
warm to room temperature and then stirred for a total of 6 h.
The reaction was quenched by addition of H2O, the aqueous
For phenol 26: 1H NMR δ 7.02 (d, J ) 1.6 Hz, 1H), 6.99 (dd,
J ) 8.1, 1.8 Hz, 1H), 6.97 (d, J ) 16.6 Hz, 1H), 6.92 (s, 2H), 6.88
(d, J ) 8.1 Hz, 1H), 6.87 (d, J ) 16.2 Hz, 1H), 5.72 (br s, 1H),
5.24 (s, 4H), 5.24 (tm, J ) 6.9 Hz, 1H), 5.07 (tm, J ) 6.9 Hz,
1H), 3.93 (s, 3H), 3.50 (s, 6H), 3.40 (d, J ) 7.4 Hz, 2H), 2.07-
2.00 (m, 2H), 2.00-1.93 (m, 2H), 1.79 (s, 3H), 1.65 (s, 3H), 1.57
(s, 3H); 13C NMR δ 155.9 (2C), 146.7, 145.5, 136.5, 134.6, 131.2,
129.9, 128.2, 126.6, 124.3, 122.6, 120.4, 119.6, 114.5, 108.1, 105.9
(2C), 94.4 (2C), 55.94 (2C), 55.85, 39.8, 26.7, 25.6, 22.7, 17.6,
16.0; EIMS, m/z (relative intensity) 482 (M+, 70), 437 (3), 359
(30), 46 (100); HR FAB-MS calcd for C29H38O6Na 505.2566, found
505.2578.
2-Met h oxy-4-((E)-4-(2(E)-3,7-d im et h yl-2,6-oct a d ien yl)-
3,5-bis(m eth oxym eth oxy)p h en yleth en yl)p h en ol (26). TBAF
(0.20 mL, 1.0 M in THF, 0.2 mmol) was added to silane 25 (119
mg, 0.20 mmol) in THF (15 mL) at 0 °C. After the solution was
stirred for 90 min, the reaction was quenched by addition of H2O
and EtOAc, and the aqueous layer was extracted with EtOAc.
The combined organic layers were dried (MgSO4) and concen-
trated in vacuo to yield compound 26 as a yellow oil (78 mg,
81%), identical with material obtained above.
6-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-4-((E)-4-(2(E)-3,7-
d im et h yl-2,6-oct a d ien yl)-3,5-b is(m et h oxym et h oxy)p h en -
yleth en yl)-2-m eth oxyp h en ol (27). Small slices of metallic
sodium (13 mg, 0.54 mmol) were added to phenol 26 (43 mg,
0.089 mmol) in Et2O (4 mL) and the mixture stirred at room
temperaturefor 3 h. Geranyl bromide (0.04 mL, 0.20 mmol) was
then added, along with Et2O (11 mL), and the solution was
heated at reflux for 16 h. After the reaction had cooled to room
temperature, it was quenched by addition of H2O, and the
aqueous layer was extracted with EtOAc. The combined organic
layers were washed with brine, dried (MgSO4), and concentrated
in vacuo. Purification by flash column chromatography (12:1
hexanes/EtOAc) afforded the C-alkylated stilbene 27 (8 mg,
14%), along with the O-alkylated product 28 (3 mg, 6%) and

Notes
J . Org. Chem., Vol. 64, No. 23, 1999 8723
phase was extracted with EtOAc, and the combined organic
layers were washed with brine, dried (MgSO4), and concentrated
in vacuo. Purification by flash chromatography (7:1 hexanes/
EtOAc) afforded compound 32 (108 mg, 54%) as a clear oil: 1H
NMR δ 6.98 (d, J ) 1.8 Hz, 1H), 6.80 (d, J ) 1.5 Hz, 1H), 5.31
(tm, J ) 7.8 Hz, 1H), 5.18 (s, 2H), 5.10 (tm, J ) 7.4 Hz, 1H),
5.08 (s, 2H), 4.63 (s, 2H), 3.59 (s, 3H), 3.49 (s, 3H), 3.41 (d, J )
6.9 Hz, 2H), 2.10-2.00 (m, 4H), 1.71 (s, 3H), 1.68 (s, 3H), 1.60
(s, 3H), 0.97 (t, J ) 7.9 Hz, 9H), 0.65 (q, J ) 7.9 Hz, 6H); 13C
NMR δ 149.6, 143.6, 137.3, 136.1, 135.6, 131.3, 124.3, 122.5,
120.7, 112.3, 99.0, 95.13, 64.5, 57.4, 56.0, 39.7, 28.3, 26.6, 25.6,
17.6, 16.1, 6.7 (3C), 4.5 (3C); EIMS, m/z (relative intensity) 478
(M+, 4), 446 (8), 117 (100). Anal. Calcd for C27H46O5Si: C, 67.74;
H, 9.68. Found: C, 67.97; H, 9.67.
5-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-3,4-b is(m et h oxy-
m eth oxy)ben zyl Alcoh ol (33). TBAF (0.19 mL, 1.0 M in THF,
0.19 mmol) was added dropwise to a solution of silane 32 (83
mg, 0.17 mmol) in THF (10 mL) at 0 °C. After the solution was
stirred for 5 h, the reaction was quenched by addition of
saturated NH4Cl. The aqueous layer was extracted with EtOAc,
and the combined organic layers were washed with brine, dried
(MgSO4), and concentrated in vacuo to afford a clear oil (60 mg,
96%). Although this material was one spot by TLC, an analytical
sample was prepared by purification by flash column chroma-
tography (1.5:1 hexanes/EtOAc): 1H NMR δ 7.01 (d, J ) 1.7 Hz,
1H), 6.84 (d, J ) 1.4 Hz, 1H), 5.31 (tm, J ) 7.1, 1H), 5.19 (s,
2H), 5.10 (s, 2H), 5.10 (m, 1H), 4.59 (s, 2H), 3.60 (s, 3H), 3.50 (s,
3H), 3.42 (d, J ) 7.3 Hz, 2H), 2.10-2.00 (m, 4H), 1.71 (s, 3H),
1.68 (s, 3H), 1.60 (s, 3H); 13C NMR δ 149.8, 144.1, 136.9, 136.3,
136.2, 131.4, 124.2, 122.4, 121.6, 112.8, 99.0, 95.1, 65.2, 57.4,
56.2, 39.7, 28.3, 26.6, 25.7, 17.7, 16.1; EIMS, m/z (relative
intensity) 364 (M+, 1), 135 (50), 69 (100). Anal. Calcd for
C21H32O5: C, 69.20; H, 8.85. Found: C, 68.94; H, 8.76.
5-((2E)-3,7-Dim et h yl-2,6-oct a d ien yl)-3,4-b is(m et h oxy-
m eth oxy)ben za ld eh yd e (34). Alcohol 33 (40 mg, 0.11 mmol)
in CH2Cl2 (5 mL) was added dropwise to a suspension of PDC
(85 mg, 0.23 mmol) and 3 Å molecular sieve powder (98 mg) in
CH2Cl2 (15 mL). After the mixture was stirred at room temper-
ature for 2.5 h, the solution was filtered through silica gel, and
the silica gel was washed thoroughly with EtOAc. After concen-
tration in vacuo, the crude product was purified by column
chromatography (2:1 hexanes/EtOAc) to afford aldehyde 34 (38
mg, 96%) as a clear oil: 1H NMR δ 9.86 (s, 1H), 7.52 (d, J ) 1.5
Hz, 1H), 7.39 (d, J ) 1.3 Hz, 1H), 5.33 (tm, J ) 7.2 Hz, 1H),
5.25 (s, 2H), 5.23 (s, 2H), 5.14-5.08 (m, 1H), 3.49 (d, J ) 8.1
Hz, 2H), 2.13-2.08 (m, 2H), 2.08-2.00 (m, 2H), 1.73 (s, 3H),
1.67 (s, 3H), 1.60 (s, 3H); 13C NMR δ 191.2, 150.1, 150.0, 137.2,
136.6, 132.4, 131.5, 129.0, 124.0, 121.4, 113.6, 98.9, 95.0, 57.5,
56.3, 39.6, 28.2, 26.5, 25.6, 17.6, 16.1; EIMS, m/z (relative
intensity) 362 (M+, 1), 317 (14), 135 (53), 69 (100). Anal. Calcd
for C21H30O5: C, 69.59; H, 8.34. Found: C, 69.34; H, 8.34
Tetr a k is(m eth oxym eth oxy)sch w ein fu r th in C (35). Phos-
phonate 18 (410 mg, 0.85 mmol) in THF (7 mL) was added to a
slurry of NaH (26 mg, 1.09 mmol) in THF (10 mL) at 0 °C, and
the reaction mixture was stirred for 30 min. Aldehyde 19 (248
mg, 0.69 mmol) in THF (3 mL) was then added dropwise, the
ice bath was removed, and the solution was stirred for 1 h while
it warmed to room temperature. After an additional hour at
reflux, the reaction was left to stir for 23 h and then quenched
by addition of H2O, and the aqueous phase was extracted with
EtOAc. The combined organic layers were washed with brine,
dried (MgSO4), and concentrated in vacuo. Repeated purification
by flash chromatography (9:1 hexanes/EtOAc) afforded com-
pound 35 (279 mg, 59%) as a clear oil: 1H NMR δ 7.15 (d, J )
1.8 Hz, 1H), 6.97 (d, J ) 1.7 Hz, 1H), 6.96 (d, J ) 15.6 Hz, 1H),
6.91 (s, 2H), 6.89 (d, J ) 16.2 Hz, 1H), 5.34 (tm, J ) 7.2 Hz,
1H), 5.24 (s, 2H), 5.23 (s, 4H), 5.23 (m, 1H), 5.12 (s, 2H), 5.07
(m, 2H), 3.61 (s, 3H), 3.54 (s, 3H), 3.50 (s, 6H), 3.43 (d, J ) 7.7
Hz, 2H), 3.40 (d, J ) 7.8 Hz, 2H), 2.15-2.00 (m, 6H), 2.00-1.90
(m, 2H), 1.79 (s, 3H), 1.75 (s, 3H), 1.68 (s, 3H), 1.65 (s, 3H), 1.60
(s, 3H), 1.57 (s, 3H); 13C NMR δ 155.9 (2C), 149.9, 144.3, 136.4,
136.3, 136.1, 134.7, 133.5, 131.4, 131.2, 128.1, 128.0, 124.4, 124.3,
122.6, 122.5, 121.7, 119.8, 111.6, 106.1 (2C), 98.1, 95.1, 94.5 (2C),
57.5, 56.3, 56.0 (2C), 39.8, 39.7, 28.5, 26.7, 26.6, 25.7, 25.6, 22.7,
17.7, 17.6, 16.3, 16.1; HR FAB-MS calcd for
715.4186, found 715.4184.
C42H60O8Na
Sch w ein fu r th in C (3). To a solution of compound 35 (38 mg,
0.054 mmol) in MeOH (2 mL) was added 3 M HCl (0.5 mL), and
the resulting solution was heated at reflux for 24 min. After the
reaction mixture had cooled to room temperature, it was
quenched by addition of saturated NaHCO3 and then extracted
with EtOAc. The combined organic layers were washed with
brine, dried (MgSO4), and concentrated in vacuo. Purification
by flash column chromatography (96:4 CHCl3/MeOH) afforded
compound 3 as a yellow oil (14 mg, 51%). This material was
identical to the natural product in direct TLC comparisons with
an authentic sample as well as in comparison of 1H and 13C NMR
data with literature values.1
Ack n ow led gm en t. We thank J ohn A. Beutler for
both helpful discussions and an authentic sample of
schweinfurthin C. Financial support from the Roy J .
Carver Charitable Trust and the University of Iowa
Graduate College is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: The 1H and/or 13C
data for 10 compounds (13, 14, 17, 18, 21, 23, 26-28, and 35).
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O9908795