A modular and concise total synthesis of (±)-daurichromenic acid and analogues

Article abstract of DOI:10.1021/jo049703f

A modular and concise total synthesis of (±)-daurichromenic acid has been accomplished in four steps from ethyl acetoacetate, ethyl crotonate, and trans,trans-farnesal. A series of analogues of this natural product, which has potent anti-HIV activity, were also prepared from ethyl or methyl acetoacetate and a series of readily available α,β-unsaturated esters and aldehydes.

Full text of DOI:10.1021/jo049703f

A Mod u la r a n d Con cise Tota l Syn th esis of (()-Da u r ich r om en ic
Acid a n d An a logu es
Hongjuan Hu, Tyler J . Harrison, and Peter D. Wilson*
Department of Chemistry, Simon Fraser University, 8888 University Drive,
Burnaby, British Columbia, Canada V5A 1S6
pwilson@sfu.ca
Received February 20, 2004
A modular and concise total synthesis of (()-daurichromenic acid has been accomplished in four
steps from ethyl acetoacetate, ethyl crotonate, and trans,trans-farnesal. A series of analogues of
this natural product, which has potent anti-HIV activity, were also prepared from ethyl or methyl
acetoacetate and a series of readily available R,â-unsaturated esters and aldehydes.
In tr od u ction
Two novel chromane derivatives, rhododaurichromanic
acid A (1) and B (2), as well as the known chromene
derivative, daurichromenic acid (3), have been isolated
recently from the leaves and twigs of Rhododendron
dauricum (Figure 1).1 The isolation of daurichromenic
acid (3) has also been reported previously by other
researchers.2 The molecular structure and absolute ster-
eochemistry of rhododaurichromanic acid A (1) was
established by X-ray crystallography. The molecular
structure and absolute stereochemistry of rhododau-
richromanic acid B (2) and daurichromenic acid (3) were
established indirectly as daurichromenic acid (3) can be
converted to rhododaurichromanic acid A (1) and B (2)
by photochemical methods.1 It was assumed that the
trans C11-C12 double bond of daurichromenic acid (3)
was isomerized to cis under the reaction conditions prior
to the photochemical cyclization reaction that afforded
rhododaurichromanic acid B (2).
Daurichromenic acid (3) was shown to have potent
anti-HIV activity [EC50 ) 0.00567 µg/mL, therapeutic
index (TI) of 3,710]. Rhododaurichromanic acid A (1) also
showed relatively potent anti-HIV activity [EC50 ) 0.37
µg/mL, TI ) 91.9], whereas rhododaurichromanic acid B
(2) was inactive.1 Recently, the total syntheses of methyl
(()-daurichromenic ester (8) as well as (()-rhododau-
richromanic acid A (1) and B (2) have been reported by
Hsung and co-workers (Scheme 1).3 Condensation and
concomitant electrocyclization of trans,trans-farnesal (4)
with the symmetrical 1,3-cyclohexanedione 5 on heating
with piperidine and acetic anhydride afforded the 2H-
pyran 6. The latter compound was converted to the
methyl ester 7, which in turn was dehydrogenated with
2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to afford
methyl (()-daurichromenic ester (8). Unfortunately, these
F IGURE 1. Molecular structures of rhododaurichromanic acid
A (1), rhododaurichromanic acid B (2), and daurichromenic
acid (3).
researchers were not able to identify suitable reaction
conditions to effect the hydrolysis of methyl ester 8 in
order to complete a total synthesis of (()-daurichromenic
acid (3). Subsequent photochemical cyclization and sa-
ponification of methyl (()-daurichromenic ester (8) af-
forded a mixture of (()-rhododaurichromanic acid A (1)
and B (2).
More recently, an efficient and concise total synthesis
of (()-daurichromenic acid (3) has been reported by J in
and co-workers (Scheme 2).4 The â-trimethylsilyl ethyl
ester 10, which was elaborated in three steps from orcinol
(9), was condensed with trans,trans-farnesal (4) on heat-
ing in a microwave oven. Subsequent deprotection of the
product of this reaction, the ester 11, afforded (()-
daurichromenic acid (3). The corresponding ethyl ester
of compound 10 was also condensed with trans,trans-
farnesal (4) under these reaction conditions (70% yield).
However, the hydrolysis (3 M NaOH, MeOH, H2O, 40 °C)
of the product of this reaction was slow and afforded (()-
daurichromenic acid (3) in relatively low yield (40%). (()-
Daurichromenic acid (3) was also converted photochem-
(1) Kashiwada, Y.; Yamazaki, K.; Ikeshiro, Y.; Yamagishi, T.;
Fujioka, T.; Mihashi, K.; Mizuki, K.; Cosentino, L. M.; Fowke, K.;
Morris-Natschke, S. L.; Lee, K.-H. Tetrahedron 2001, 57, 1559.
(2) J pn. Kokai Tokkyo Koho, J P 82-28,080, 1982.
(3) Kurdyumov, A. V.; Hsung, R. P.; Ihlen, K.; Wang, J . Org. Lett.
2003, 5, 3935.
(4) Kang, Y.; Mei, Y.; Du, Y.; J in, Z. Org. Lett. 2003, 5, 4481.
10.1021/jo049703f CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/24/2004
3782
J . Org. Chem. 2004, 69, 3782-3786

Total Synthesis of (()-Daurichromenic Acid and Analogues
SCHEME 1. Syn th esis of Meth yl (()-Da u r ich r o-
m en ic Ester (8) a n d (()-Rh od od a u r ich r om a n ic
Acid A (1) a n d B (2) by Hsu n g et a l.3
F IGURE 2. Retrosynthetic analysis of (()-daurichromenic
acid and analogues 12.
SCHEME 2. Syn th esis of (()-Da u r ich r om en ic Acid
(3) by J in et a l.4
F IGURE 3. 1,3-Cyclohexanedione precursors 18-22.
crotonate on reaction with sodium ethoxide in 81% yield.7
The 1,3-cyclohexanedione 19 was prepared from methyl
acetoacetate and methyl cinnamate on reaction with
sodium methoxide in 61% yield.7a,8 This demonstrated
that a variety of substituents can potentially be intro-
duced at C7 in the daurichromenic acid analogues.
Unfortunately, it was not possible to prepare the C5-
substituted, C5,C6-disubstituted, or the monosubstituted
cyclohexanediones 20-22 from methyl acetoacetate and
the corresponding commercially available R,â-unsatur-
ated methyl esters by this direct one-pot procedure.
The R,â-unsaturated aldehydes selected for study
included commercially available 3-methyl-2-butenal (sene-
cialdehyde) (23), 3,7-dimethyl-2,6-octadienal (citral, E/Z
) ∼2:1) (24), and cyclohexene-1-carboxaldehyde (25)
(Figure 4). In addition, trans,trans-farnesal (4) was
prepared from commercially available trans,trans-farne-
ically to (()-rhododaurichromanic acid A (1) and B (2)
(40 and 20% yield, respectively) by these researchers.
In this paper, we report a modular and concise total
synthesis of (()-daurichromenic acid (3) and a series of
structural analogues. Our retrosynthetic analysis of the
target compounds 12 is illustrated below (Figure 2). It
was conceived independently that (()-daurichromenic
acid and a series of analogues 12 could be prepared from
the 2H-pyrans 13 by a dehydrogenation (oxidation/
aromatization) reaction and a subsequent ester hydroly-
sis reaction. The 2H-pyrans 13 could be prepared in a
convergent manner from the unsymmetrical 1,3-cyclo-
hexanediones 14 and a series of R,â-unsaturated alde-
hydes 15 employing a condensation and concomitant
electrocyclization reaction.5,6 The 1,3-cyclohexanedione
precursors 14 would in turn be available from the alkyl
acetoacetates 16 and a series of R,â-unsaturated esters
17 employing a conjugate addition and concomitant
intramolecular condensation reaction.
(5) The formation of 2H-pyrans from 1,3-dicarbonyl compounds and
R,â-unsaturated aldehydes via the Knoevenagel condensation reaction
is well established; see: (a) Tietze, L. F.; Beifuss, U. In Comprehensive
Organic Synthesis; Trost, B. M., Ed.; Heathcock, C. H., Vol. Ed.;
Pergamon Press: Oxford, 1992; Vol. 2, p 341. (b) Shen, H. C.; Wang,
J .; Cole, K. P.; McLaughlin, M. J .; Morgan, C. D.; Douglas, C. J .; Hsung,
R. P.; Coverdale, H. A.; Gerasyuto, A. I.; Hahn, J . M.; Liu, J .; Sklenicka,
H. M.; Wei, L.-L.; Zehnder, L. R.; Zificsak, C. A. J . Org. Chem. 2003,
68, 1729 and references therein (see also ref 3).
(6) Recently, our research group has reported a related condensation
reaction of a dibenzo-oxepinone with citral and senecialdehyde which
was employed as a key step in the synthesis of the polycyclic ring
systems of artocarpol A and D; see: Paduraru, M. P.; Wilson, P. D.
Org. Lett. 2003, 5, 4911.
Resu lts a n d Discu ssion
(7) (a) Gould, S. J .; Cheng, X.-C. Tetrahedron 1993, 49, 11135. (b)
Gaucher, G. M.; Shepherd, M. G. Biochem. Prepr. 1971, 13, 70.
(8) Piskov, V. B.; Kasperovich, V. P. J . Org. Chem. USSR 1985, 21,
1088.
Two 1,3-cyclohexanediones 18 and 19 were prepared
in the first instance (Figure 3). The 1,3-cyclohexanedione
18 was prepared from ethyl acetoacetate and ethyl
J . Org. Chem, Vol. 69, No. 11, 2004 3783

Hu et al.
SCHEME 4. Tota l Syn th esis of (()-Da u r ich r om en ic
Acid (3) a n d An a logu es, 32a ,b, 34a ,b, 36b, a n d 38a a
F IGURE 4. R,â-Unsaturated aldehyde precursors 23-25, 4,
and 26.
SCHEME 3. Kn oeven a gel
Con d en sa tion -Electr ocycliza tion Rea ction
P r od u cts 27a ,b, 28a ,b, 29a ,b, a n d 30a a
a
Reagents and conditions: (a) DDQ, benzene, reflux, 4-16 h;
(b) 5 M NaOH (aq), DMSO, 80 °C, ∼16 h.
mixtures of diastereoisomers in good to excellent yield
(63-90%). The 2H-pyran 29a , which is a precursor of (()-
daurichromenic acid (3), was isolated in 87% yield. This
series of efficient reactions demonstrated that a variety
of substituents can be introduced at C2 and C7 in the
daurichromenic acid analogues. However, the condensa-
tion reaction of 1,3-cyclohexanedione 18 with cyclohex-
ene-1-carboxaldehyde 25, under these reaction condi-
tions, afforded a complex mixture of products from which
it was not possible to isolate the corresponding tricyclic
(C2,C3-disubstituted) analogue.
A broad spectrum of reagents and reaction conditions
were screened in order to effect the dehydrogenation
reaction of the products of the latter reactions (the 2H-
pyrans 27a ,b, 28a ,b, 29a ,b, and 30a ).12,13 It was found
independently that heating these esters with DDQ at
reflux in benzene for 4-16 h afforded the desired aro-
matized reaction products in low to moderate yield (6-
43%) (Scheme 4). However, these reactions can be
performed on a relatively large scale, and significant
quantities of the desired analytically pure reaction
a
Reagents and conditions: (a) 5 mol % H2NCH2CH2NH2, 10
mol % AcOH, MeOH, rt, 3-16 h.
sol on oxidation with pyridinium dichromate (buffered
with sodium bicarbonate) in 96% yield.3,4 Cyclohexyli-
deneacetaldehyde (26) was also prepared in 39% overall
yield from cyclohexanone on addition of vinylmagnesium
bromide and subsequent oxidation of the resultant
tertiary allylic alcohol with pyridinium chlorochromate.9
Condensation of 1,3-cyclohexanedione 18 in methanol
with senecialdehyde (23), citral (24), trans,trans-farnesal
(4), and cyclohexylideneacetaldehyde (26), at room tem-
perature in the presence of 5 mol % of 1,2-ethylenedi-
ammonium diacetate for ∼3 h, afforded the expected
substituted 2H-pyrans 27a -29a and the spirocyclic 2H-
pyran 30a (Scheme 3).10,11
The tandem Knoevenagel condensation-electrocycliza-
tion reaction was also used to prepare three phenyl-
substituted derivatives 27b-29b from 1,3-cyclohexanedi-
one 19 and senecialdehyde (23), citral (24), and trans,
trans-farnesal (4) (at room temperature for ∼16 h). All
of the 2H-pyran derivatives were isolated as inseparable
(12) Various dehydrogenation reaction conditions (employing for
example: Pd/C, chloranil, NCS, NBS, TEMPO, Br2, o-iodoxybenzoic
acid, Pd(OAc)2, CuCl2, MnO2, SeO2, ceric ammonium nitrate, peroxides,
molecular oxygen, and vitamin B2 as reagents) either proved to be
unreactive, caused extensive decomposition of the starting materials,
or resulted in isolation of the desired reaction products in low yield.
Similarly, attempted oxidation of the corresponding silyl enol ether
derivatives of these substrates was low yielding.
(9) (a) Mason, T. L.; Harrison, M. J .; Hall, J . A.; Sargent, G. D. J .
Am. Chem. Soc. 1973, 95, 1849. (b) Dauben W. G.; Michno, D. M. J .
Org. Chem. 1977, 42, 682.
(10) Tietze, L. F.; von Kiedrowski, G.; Berger, B. Synthesis 1982,
683.
(13) Tietze has commented that related 2H-pyrans that have
substituents incorporating carbon-carbon double bonds are difficult
to dehydrogenate selectively. He developed a two-step procedure to
effect this transformation (LDA, THF, then PhSeCl; m-CPBA then 3,5-
dimethoxyaniline; see ref 10). In this instance, these reaction conditions
proved to be less than satisfactory.
(11) The 1H NMR spectrum (see the Supporting Information) of the
trans,trans-farnesal-derived 2H-pyran 29a was very similar to the
related compound 7 (see Scheme 1) prepared by Hsung and co-workers;
see ref 3 (Supporting Information).
3784 J . Org. Chem., Vol. 69, No. 11, 2004

Total Synthesis of (()-Daurichromenic Acid and Analogues
improve the yield of the dehydrogenation step and
additional structural analogues are being prepared by
this method. In addition, the synthetic route is being
adapted for use in polymer-supported synthesis and
alternative modular and concise syntheses of dau-
richromenic acid analogues are under active investiga-
tion.
F IGURE 5. Regioisomeric Knoevenagel condensation-elec-
trocyclization reaction products 39 and dehydrogenation prod-
ucts 40.
Exp er im en ta l Section
products 31a ,b, 33a ,b, 35a ,b, and 37a were isolated
chromatographically. The aromatic ethyl ester 35a , which
is the direct precursor of (()-daurichromenic acid (3), was
isolated in 11% yield.14,15 Following considerable experi-
mentation, it was found that all of these aromatic
o-hydroxy esters could be saponified with an aqueous 5
M solution of sodium hydroxide (∼10 equiv) in dimethyl
sulfoxide (DMSO) on heating at 80 °C for ∼16 h.16
The latter procedure afforded significant quantities of
the desired target compounds, (()-daurichromenic acid
(3) and the analogues 32a ,b, 34a ,b, 36b, and 38a , in
moderate to high yield (38-89%). The saponification
reactions of the methyl and ethyl esters of (()-dau-
richromenic acid have been reported to be problematic
(due to a facile decarboxylation reaction of the product).3,4
In this instance, (()-daurichromenic acid (3) was isolated
in good yield (76%). The spectroscopic data for (()-
daurichromenic acid (3) were in full agreement with those
reported for the natural product.1 Of note and in regard
to the regioselectivity of the Knoevenagel condensation-
electrocyclization reaction, we have not isolated nor do
we have any spectroscopic data of crude reaction products
to indicate that the regioisomeric products 39 were
formed (Figure 5). Similarly, the regioisomeric dehydro-
genation products 40 were not isolated from any of the
reactions.
2,7-Dim eth yl-2-(4,8-d im eth yl-3E,7-n on a d ien yl)-5-oxo-
5,6,7,8-tetr a h yd r o-2H-ch r om en e-6-ca r boxylic Acid Eth yl
Ester (29a ). Rep r esen ta tive P r oced u r e for th e F or m a -
tion of 2H-P yr a n s (27a ,b, 28a ,b, 29b, a n d 30a ). To a
mixture of 1,2-ethylenediamine (20 µL, 0.30 mmol) and acetic
acid (34 µL, 0.59 mmol) in dry methanol (10 mL) was added
the ester 18 (1.16 g, 5.83 mmol) at room temperature. After
30 min, trans,trans-farnesal (4) (1.17 g, 5.30 mmol) was added.
After 3 h, the solvent was removed in vacuo, and the yellow
residue was dissolved in ethyl acetate (20 mL) and washed
with water (2 × 10 mL), a saturated aqueous solution of
sodium bicarbonate (2 × 10 mL), and then brine (10 mL). The
organic layer was dried over anhydrous sodium sulfate and
concentrated in vacuo, and the resultant residue was purified
by flash chromatography using ethyl acetate/hexanes (4%) as
the eluant to afford the title compound 29a (1.85 g, 87%) as a
pale yellow oil: 1H NMR (400 MHz, C6D6) δ 0.72 (d, J ) 6.4
Hz, 3H), 1.02 (t, J ) 7.1 Hz, 3H), 1.10 (s, 3H), 1.57 (apparent
s, 6H), 1.63 (m, 2H), 1.67 (s, 3H), 2.02 (m, 2H), 2.08 (m, 4H),
2.17 (m, 2H), 2.38 (m, 1H), 2.88 (d, J ) 11.6 Hz, 1H), 4.09 (m,
2H), 4.80 (d, J ) 10.1 Hz, 1H), 5.20 (m, 2H), 6.73 (d, J ) 10.1
Hz, 1H); 13C NMR (101 MHz, C6D6) δ (mixture of isomers,
major signals reported) 14.3, 16.0, 17.7, 19.5, 22.7, 23.0, 27.1,
30.8, 35.2, 40.1, 60.6, 60.8, 82.4, 82.5, 109.6, 109.7, 117.0, 117.1,
124.07, 124.11, 124.7, 124.8, 131.31, 131.34, 135.7, 169.8,
170.0, 170.08, 170.13, 188.9, 190.0; IR (ef) 2967, 1739, 1655,
1597, 1415, 1326, 1254, 1157 cm-1; MS (CI) m/z (rel intensity)
401 (M + H, 100); FAB HRMS calcd for C25H36O4 m/z 400.2614,
found m/z 400.2611.
5-H yd r oxy-2,7-d im et h yl-2-(4,8-d im et h yl-3E,7-n on a d i-
en yl)-2H-ch r om en e-6-ca r boxylic Acid Eth yl Ester (35a ).
Rep r esen ta tive P r oced u r e for th e F or m a tion of Ester s
(31a ,b, 33a ,b, 35b, a n d 37a ). To a solution of the ester 29a
(580.0 mg, 1.46 mmol) in benzene (16 mL) was added DDQ
(497.2 mg, 2.20 mmol) at room temperature. The reaction
mixture was then heated at reflux for 16 h. On cooling, the
resultant mixture was filtered through a pad of basic alumina
with ethyl acetate (160 mL). The solvent was removed in
vacuo, and the dark red residue was purified by flash chro-
matography using ethyl acetate/hexanes (2%) as the eluant
to afford the title compound 35a (63.4 mg, 11%) as a yellow
oil: 1H NMR (400 MHz, CDCl3) δ 1.39 (s, 3H), 1.40 (t, J ) 7.1
Hz, 3H), 1.56 (s, 3H), 1.59 (s, 3H), 1.67 (s, 3H), 1.65-1.75 (m,
2H), 1.95 (m, 2H), 2.03 (m, 2H), 2.09 (m, 2H), 2.47 (s, 3H),
4.38 (q, J ) 7.1 Hz, 2H), 5.09 (m, 2H), 5.47 (d, J ) 10.1 Hz,
Con clu sion
A modular and concise total synthesis of (()-dau-
richromenic acid 3 has been accomplished in four steps
from trans,trans-farnesal (4) and readily available start-
ing materials (ethyl acetoacetate and ethyl crotonate).
The synthetic route was adapted to prepare a series of
daurichromenic acid analogues in which a variety of
substituents were introduced at C2 and C7. Although the
overall yield of the route is relatively low (in the case of
derivatives that have substituents that incorporate car-
bon-carbon double bonds), significant quantities of
analytically pure materials have been prepared for
subsequent biological evaluation. The results of these
investigations will be reported in due course. It is hoped
that these studies will provide insight into the structure-
activity relationships of this potent anti-HIV lead com-
pound. Further synthetic studies are in progress to
1H), 6.18 (s, 1H), 6.73 (d, J ) 10.1 Hz, 1H), 12.07 (s, 1H); 13
C
NMR (101 MHz, CDCl3) δ 14.4, 16.1, 17.8, 22.7, 24.7, 25.8,
26.8, 27.1, 39.8, 41.7, 61.3, 79.8, 105.2, 107.2, 111.8, 117.0,
123.9, 124.5, 126.4, 131.5, 135.6, 142.9, 157.9, 159.9, 172.1;
IR (ef) 3316, 2971, 1650, 1566, 1453, 1377, 1270, 1174 cm-1
;
MS (CI) m/z 399 (M + H, 100), 353 (38), 249 (14), 209 (5). Anal.
Calcd for C25H34O4: C, 75.34; H, 8.60. Found: C, 75.16; H,
8.61.
(14) Hsung and co-workers have reported that the 2H-pyran methyl
ester 7 can be dehydrogenated with DDQ on heating at reflux in
toluene (see Scheme 1). In our hands, these reaction conditions caused
extensive decomposition of the corresponding 2H-pyran ethyl ester 29a
and only a trace amount of the desired aromatic ethyl ester 35a was
isolated; see ref 3.
(15) The aromatic ethyl ester 35a has been prepared previously by
J in and co-workers. Our NMR data (see the Supporting Information)
was completely consistent with the data reported for this compound;
see ref 4 (Supporting Information).
(()-Da u r ich r om en ic Acid (3). Rep r esen ta tive P r oce-
d u r e for th e F or m a tion of Da u r ich r om en ic Acid An a -
logu es (32a ,b, 34a ,b, 36b, a n d 38a ). To a solution of the ester
35a (200.0 mg, 0.503 mmol) in DMSO (3 mL) was added an
aqueous solution of sodium hydroxide (20% w/v, 1.0 mL, 5.0
mmol) at room temperature. The reaction was then heated at
80 °C for 16 h. On cooling, water (2 mL) was added, and the
resultant solution was washed with ether (5 mL). The aqueous
(16) Elix, J . A.; Whitton, A. A. Aust. J . Chem. 1989, 42, 1969.
J . Org. Chem, Vol. 69, No. 11, 2004 3785

Hu et al.
layer was acidified with hydrochloric acid (6 M) to pH ∼2 and
extracted with dichloromethane (3 × 10 mL). The combined
organic extracts were washed with water (2 × 5 mL) and brine
(10 mL), dried over anhydrous sodium sulfate, and concen-
trated in vacuo. The dark brown crude product was then
purified by flash chromatography using methanol/dichlo-
romethane (3%) as the eluant to afford the title compound
(()-3 (140.4 mg, 76%) as a light brown syrup: 1H NMR (400
MHz, CDCl3) δ 1.41 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.67 (s,
3H), 1.66-1.77 (m, 2H), 1.95 (m, 2H), 1.97 (m, 2H), 2.04-2.12
(m, 2H), 2.54 (s, 3H), 5.09 (m, 2H), 5.48 (d, J ) 10.1 Hz, 1H),
6.24 (s, 1H), 6.74 (d, J ) 10.1 Hz, 1H), 11.66 (s, 1H); 13C NMR
(101 MHz, CDCl3) δ 16.1, 17.8, 22.7, 24.6, 25.8, 26.8, 27.3, 39.8,
41.8, 80.3, 103.7, 107.2, 112.4, 116.8, 123.9, 124.5, 126.5, 131.5,
135.7, 144.7, 159.2, 160.8, 176.4; IR (ef) 2966, 1621, 1455, 1268,
1177 cm-1; MS (CI) m/z 327 (M + H, - CO2, 100), 175 (9).
Anal. Calcd for C23H30O4: C, 74.56; H, 8.16. Found: C, 74.30;
H, 8.18.
(NSERC) and Simon Fraser University (SFU) for finan-
cial support. We also wish to acknowledge the Canadian
Foundation for Innovation (CFI) for support of our
research program. H.H. thanks SFU for graduate
research fellowships. T.J .H. thanks NSERC for an
undergraduate summer research award (USRA). We are
also grateful to Professor Y. Kashiwada for kindly
providing copies of the 1H and 13C NMR spectra of
daurichromenic acid 3 as well as a sample of the natural
product for comparison purposes.
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedures and complete product characterization data
1
for all of the additional compounds synthesized as well as H
and 13C NMR spectra for compounds (()-3, 27a ,b, 28a ,b,
29a ,b, 30a , 32a ,b, 34a ,b, 35a , 36b, and 38a . This material is
available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
J O049703F
3786 J . Org. Chem., Vol. 69, No. 11, 2004