Total syntheses of the sesquiterpenes β-corymbolol and corymbolone

Article abstract of DOI:10.1016/j.tet.2006.07.026

The first total synthesis of racemic corymbolone, an eudesmane sesquiterpene isolated from Cyperus species used in traditional medicine to treat many diseases, is reported. In the developed sequence, the immediate precursor of corymbolone is the diol β-corymbolol, an epimer at C₁ of the natural α-corymbolol. Thus, starting from the readily available Wieland-Miescher Ketone, the title compounds were achieved in 11 and 12 steps, respectively, in ca. 3% overall yield.

Full text of DOI:10.1016/j.tet.2006.07.026

Tetrahedron 62 (2006) 9232–9236
Total syntheses of the sesquiterpenes b-corymbolol and
corymbolone
y
*
Helena M. C. Ferraz, Antonio J. C. Souza, Beatriz S. M. Tenius and Graziela G. Bianco
´
Instituto de Quımica, Universidade de Sao Paulo, CP 26.077, 05513-970 Sao Paulo, SP, Brazil
~
~
Received 2 June 2006; revised 7 July 2006; accepted 7 July 2006
Available online 28 July 2006
This paper is dedicated to Professor Nicola Petragnani, for his invaluable contribution to the development of the Brazilian Organic Synthesis
Abstract—The first total synthesis of racemic corymbolone, an eudesmane sesquiterpene isolated from Cyperus species used in traditional
medicine to treat many diseases, is reported. In the developed sequence, the immediate precursor of corymbolone is the diol b-corymbolol, an
epimer at C1 of the natural a-corymbolol. Thus, starting from the readily available Wieland–Miescher Ketone, the title compounds were
achieved in 11 and 12 steps, respectively, in ca. 3% overall yield.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The reported biological activity and the rare presence of an
angular hydroxyl group, as well as the lack in the literature
of any described synthesis of these compounds, stimulated
us to investigate some approaches for their total synthesis.
Thus, starting from the readily available Wieland–Miescher
Ketone (3), we designed the retrosynthetic analysis depicted
in Scheme 1.
Corymbolone (1) is a sesquiterpenic keto-alcohol first iso-
lated in 1985, in South America, from the rhizomes of Cype-
rus corymbosus Rottboll.1 Some years later, corymbolone
was isolated in Cameroon, from Cyperus articulatus L.,
along with another eudesmane sesquiterpene, the diol a-cor-
ymbolol (2a).2 Since 1994, C. articulatus L. and C. corym-
bosus Rottb. are treated as synonymous.3 This cyperaceae
is a tropical sedge widely distributed in southern and western
Africa, where it is known as ‘mandassi’,2 as well as in the
Amazonian region, where it is called ‘piripiri’.4 The crude
drug prepared from the rhizomes of this plant has been
used in traditional medicine as contraceptive5,6 and for treat-
ing many other diseases.7,8
OPG
O
OH
1
4
10
5
7
6
OH
OH
O
2a (α-OH)
2b (β-OH)
1
4
OPG
OPG
O
Both corymbolone and corymbolol (Fig. 1) bear an axial hy-
droxyl group at the C5 position, which is not an usual feature
of the eudesmane sesquiterpenes.
O
O
O
5
6
3
Scheme 1. Retrosynthetic approach for 1 and 2.
O
OH
OH
The functionalization of the A ring of 1 involves a nucleo-
philic opening of the a-epoxide 4, by means of an adequate
organometallic reagent, followed by oxidation of the sec-
ondary hydroxyl group of 2a or 2b. Since it is well known
that the SN2-type opening of cyclohexyl oxiranes is
a trans-diaxial process, it can be foreseen that the organo-
metallic reagent would attack the less substituted center
(C4) of 4 from the b-face. Therefore, the stereoselective
a-epoxidation of 5 is a requirement to ensure the correct
introduction of the axial methyl and hydroxyl groups at C4
OH
1
OH
2a
OH
2b
Figure 1. Corymbolone (1), a-corymbolol (2a) and b-corymbolol (2b).
Keywords: Corymbolone; Corymbolol; Eudesmane sesquiterpenes; Cype-
raceae species.
* Corresponding author. Tel./fax: +55 11 3091 3851; e-mail: hmferraz@iq.
usp.br
Present address: Centro de Ciencias da Saude–UNISANTOS–Santos–SP.
y
^
ꢀ
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.026

H. M. C. Ferraz et al. / Tetrahedron 62 (2006) 9232–9236
9233
OAc
OAc
and C5, respectively. A preferential epoxidation from the
a-face could be expected, due to the steric hindrance offered
by the C10 b-methyl group.
a, b
72%
c
d
53%
3
O
79%
O
O
12
13
Concerning the B ring, the retrosynthetic analysis suggests
that the isopropenyl unit could be introduced by homologa-
tion of the carbonyl group of 6, followed by an olefination
reaction of the resulting acetyl group present in 5 (or in
some synthetic equivalent).
OH
OAc
e
O
O
89%
OH
O
O
O
14
15
Finally, the migration of the double bond from the C5–C6 to
the C4–C5 position, in an appropriate stage of the synthesis,
would complete the retrosynthetic approach. The experi-
mental results further described confirm the feasibility of
the proposed sequence.
Scheme 3. Reagents and conditions: (a) NaBH4, EtOH, 0 ꢀC, 92%; (b)
Ac2O, py, DMAP, rt, 78%; (c) ethylene glycol, p-TSA, PhH, 12 h, reflux;
(d) m-CPBA, CH2Cl2, 3 h, rt and (e) MeMgI, CuI, Et2O, 8 h, rt.10
It must be noted that some years after the publication of the
above mentioned results,10 the same sequence of reactions
(from 3 to 13) was employed by Danishefsky et al. in the
total syntheses of baccatin III and taxol.13
2. Results and discussion
In a previous paper,9 we presented the results of our attempts
to promote the stereoselective a-epoxidation of the b,g-
unsaturated ketone 8, obtained by deconjugation of 7. By
this first proposed protocol, the resulting product 9 would
be submitted to a Horner–Emmons olefination, followed
by hydrolysis, to furnish the advanced intermediate 10. How-
ever, this sequence could not be achieved, since the desired
epoxide 9 was obtained in very low yield (30%), accompa-
nied by the reconjugated ketone 7 as the major product.
Moreover, the epoxide 9 showed to be very unstable, even
at 0 ꢀC, and when submitted to the olefination reaction
gave exclusively the allylic alcohol 11, in 84% yield
(Scheme 2). The formation of this alcohol can be rational-
ized on the basis of a deprotonation at C6, with subsequent
opening of the epoxide ring.
The epoxidation of 13 was performed by classical conditions
(m-CPBA in dichloromethane), giving a diastereomeric mix-
ture (ca. 7:3, by H NMR analysis) of the epoxides, which
1
were separated by silica column chromatography into the
pure a-isomer 14 (53%) and the corresponding b-isomer
(19%). The correct structure of 14 was determined by
NMR spectroscopy, and confirmed by X-ray analysis.14
Although a greater ratio of the desired a-epoxide had been
expected a priori, the lower assessed a/b ratio can be prob-
ably attributed to a competitive hindrance between the C10
b-methyl group and the a-oxygen of the ketal group at C7.
Other epoxidizing reagents (DMD and TBHPMo) were
then tried, not only on the intermediate 13, but also on other
related substrates.15 The results thus obtained were more
unfavourable, since the major isomers were always the
b-epoxides. We have then decided to pursuit the synthetic
route using the earlier protocol (m-CPBA-promoted epoxi-
dation of 13), in spite of the moderate yield of 14.
O
O
O
O
O
O
a
b
92%
30%
O
O
O
O
9
7
8
c
The trans-diaxial opening of the epoxide 14 was best per-
formed employing methylmagnesium iodide in the presence
of 10% of cuprous iodide, although with loss of the protect-
ing group at C1. Eventually, the presence of the copper salt
should preserve the chemoselectivity towards the epoxide
ring, therefore avoiding the attack to the acetyl group.
Nevertheless, a great excess of the Grignard reagent was
required to achieve good results in the epoxide opening,
since 2 equiv were consumed by the acetate group, giving
the diol 15 as final product. At this point, the synthetic prob-
lems concerning the construction of the ring A of the target
molecule were solved.
X
84%
O
O
O
O
O
d
SMe
O
O
O
OH
O
10
11
Scheme 2. Reagents and conditions: (a) i: t-BuOK/t-BuOH, 1 h, rt; ii:
NaH2PO4 0.3 M;(b)m-CPBA, CH2Cl2, 2 h, rt;(c)(EtO)2P(O)CHCH3(SMe),
THF, 4 h, ꢁ78 ꢀC and (d) H3O+.9
In view of these disappointing results, we formulated a sec-
ond synthetic approach,10 where none of the intermediates
has acidic protons at C6, for circumventing the undesirable
reactions mentioned above. The envisaged key-intermediate
of the new sequence was the a-epoxide 14, which could be
obtained from the ketone 3 (Scheme 3).
The introduction of the isopropenyl unit at C7, as stated in
the retrosynthetic analysis, would be possible following a se-
quence of reactions already employed by Heathcock et al.,12
and by de Groot et al.,16 in their syntheses of other eudes-
mane sesquiterpenes. The approach consists in a Wittig reac-
tion at the C7 carbonyl group, followed by hydroboration of
the C7–C11 double bond, oxidation of the hydroxyl group at
C11 and, finally, another olefination of the resulting methyl
ketone.
Thus, the acetate 12 was easily obtained by reduction11 and
acetylation12 of 3. The deconjugative ketalization of 12 was
undertaken by treatment with ethylene glycol in the presence
of p-TSA, leading to 1312 as a white crystalline solid.

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H. M. C. Ferraz et al. / Tetrahedron 62 (2006) 9232–9236
OAc
OAc
OH
a
b
c
O
O
75%
94%
52%
O
OH
15
O
OH
16
O
OH
17
OAc
OAc
OAc
d
e
64%
75%
OH
19a/19b
OH
20a
OH
OH
O
18a/18b
(E/Z, 1:1)
OAc
OAc
OH
O
g
74%
f
76%
O
OH
20b
OH
OH
2b
O
OH
21
1
Scheme 4. Reagents and conditions: (a) Ac2O, Et3N, DMAP, 72 h, rt; (b) AcOH, 20 min, 65ꢀC; (c) Ph3P]CHCH3, DMSO, 15 min, rt; (d) i: BH3$THF, 21 h, rt;
ii: NaOH 3 N, H2O2, 15 min, rt; (e) PCC, AcONa, CH2Cl2, 3 h, rt; (f) Ph3P]CH2, DMSO, 7 h, 50ꢀC and (g) PCC, CH2Cl2, 3 h, rt.
The complete sequence from 15 to 1, and hence to 2b, was
accomplished with success, as summarized in Scheme 4.
acceptable, since it was recompensed by accomplishing
the conversion of 17 into 18 in a single step, avoiding the
protection (and subsequent deprotection) of the hydroxyl
group at C5.
Since the first step in the construction of the ring B would be
a Wittig olefination of the regenerated carbonyl group at C7,
the protection of both the hydroxyl groups in 15 seemed to
be a requirement. We attempted at first the diacetylation of
15, by treatment with Ac2O/Et3N under DMAP catalysis.
Unfortunately, several experiments employing these condi-
tions, as well as changing Et3N for pyridine, and running
the reaction at different times and temperatures, furnished
exclusively the monoacetylated derivative 16. Attempts to
protect the C5 hydroxyl group of 16 with different alkoxy
groups were also fruitless.
The regioselective hydroboration of 18 gave mainly, as
expected, the anti-Markovnikov product 19 (75% yield,
after silica column chromatography), together with minor
amounts of its regioisomer. The stereoselectivity of the reac-
tion was remarkably high, with the hydroxyalkyl substituent
at C7 assuming exclusively the undesired a-axial position.
Probably, this high stereoselectivity is due to the steric
hindrance offered by the axial hydroxyl group at C5.
Considering the relative configurations of corymbolone and
a-corymbolol, an essential requirement for pursuing the
synthesis would be the axial to equatorial inversion of the
hydroxyalkyl substituent at C7. An obvious attempt involves
the oxidation of 19, expecting that the produced methyl
ketone (20a) would assume the thermodynamically more
stable equatorial position (20b). Nevertheless, the oxidation
of 19, using PCC in the presence of AcONa, led directly to
the lactol 21, instead of the expected methyl ketone.
In view of this somewhat surprising stability of 15 and 16 to-
wards both acidic and basic media, we decided to disregard
the protection of the tertiary alcohol and to submit the ketone
17 directly to the Wittig reaction. It must be pointed out that
a successful Wittig reaction in a hydroxylated substrate has
already been reported.16 In a first set of experiments, 17 was
treated with excess (ranging from 2 to 5 equiv) of ethylidene
triphenylphosphorane in ethyl ether, at room temperature,
furnishing the desired olefin 18 as a mixture of E and Z iso-
mers, in poor yields. The main product of these reactions
was the a,b-unsaturated ketone formed by dehydration of
17. Under these conditions, the best yield of 18 was 29%.
Fortunately, the desired epimerization of C7 was success-
fully achieved by submitting the lactol 21 to a Wittig reac-
tion with methylene triphenylphosphorane. The highly
basic medium of the reaction promoted the opening of the
hemiketal 21, followed by equilibration to 20b, which was
then converted irreversibly into the olefinic product. The
conditions employed—warming at 50 ꢀC—also promoted
the deprotection of the hydroxyl group at C1, in contrast to
that observed in the olefination of 17, performed at room
temperature.
Assuming that the low yield of 18 could be due not only to
the concurrence of the elimination reaction, but also to the
low solubility of 17 in ethyl ether, a set of experiments
was performed using DMSO as the solvent (where the sub-
strate is more soluble) and the corresponding lithium dimsyl
as the base. Under these conditions, and using 2 equiv of the
phosphonium salt, the desired olefin 18 was obtained in
a considerably increased yield. A rigorous control of the re-
action time showed to be necessary, the best result (52%
yield) being achieved after 15 min at room temperature.
Although quite modest, this yield can be considered
Therefore, to our delight, b-corymbolol (2b) was obtained in
a single step from the lactol 21, in 74% yield. Finally, the
oxidation of 2b to corymbolone (1) was performed in 76%
yield, by treatment with PCC.

H. M. C. Ferraz et al. / Tetrahedron 62 (2006) 9232–9236
9235
In summary, the first total syntheses of racemic b-corymbo-
lol and corymbolone was accomplished in 11 and 12 steps,
respectively, from the commercially available Wieland–
Miescher Ketone (3). As the enantiomerically pure ketone
3 can be easily prepared,17,18 the approach herein reported
could be adapted for the chiral synthesis of the title com-
pounds. Since a-corymbolol (2a) was already obtained by
reduction of corymbolone,2 our sequence also represents
a racemic formal synthesis of this natural product.
2935, 1726, 1699, 1256 cmꢁ1; MS (EI) m/z (%) 254 (Mꢂ+,
2), 109 (100); Anal. Calcd for C14H22O4: C¼66.12%,
H¼8.72%; Found: C¼66.51%, H¼9.05%.
3.4. E- and Z-1b-Acetoxy-4b,10b-dimethyl-5a-hydroxy-
7-ethylidene decalin (18a/18b)
n-BuLi (1.7 M in hexane; 2.1 mL, 3.5 mmol) was added to
anhydrous DMSO (20 mL), under N2 atmosphere. After stir-
ring for 30 min, ethyl triphenylphosphonium bromide (1.6 g;
4.3 mmol) was added and the mixture was stirred for 1 h at
room temperature. A solution of 17 (0.40 g; 1.6 mmol) in an-
hydrous DMSO (10 mL) was added, the mixture was stirred
for 15 min at room temperature and then poured into H2O
(100 mL). After extraction with AcOEt, the organic layer
was washed with satd NaCl solution, dried over Na2SO4
and concentrated under reduced pressure. The crude product
was chromatographed on silica gel (hexanes/AcOEt, 9:1 as
eluent) to give a 1:1 mixture of 18a/18b (52%; 0.22 g,
0.83 mmol). 1H NMR d 5.50 (q, J 6.6 Hz, 1/2H), 5.23 (q, J
6.7 Hz, 1/2H), 5.08 (dd, J 10.4, 5.7 Hz, 1H), 2.90–1.20 (m,
15H), 2.00 (s, 3H), 1.16 (s, 3H), 1.06 (d, J 8.1 Hz, 3/2H),
1.02 (d, J 8.2 Hz, 3/2H); 13C NMR d 170.8, 135.7/135.5,
121.9/121.7, 77.4, 76.8/76.4, 43.6, 42.2, 39.2/39.1, 35.7/
35.3, 34.9/31.3, 26.4, 22.9/22.8, 21.2, 16.6/16.5, 16.1/15.8,
12.9/12.6; IR (film) nmax: 3509, 2959, 2931, 1714,
1263 cmꢁ1; MS (EI) m/z (%) 266 (Mꢂ+, 2), 124 (100);
Anal. Calcd for C16H26O3: C¼72.14%, H¼9.84%; Found:
C¼71.71%, H¼9.53%.
3. Experimental
3.1. General
Melting points (Kofler hot-stage) are uncorrected. 1H NMR
spectra were recorded at 200 MHz on a Bruker AC-200
spectrometer, in CDCl3, using TMS as an internal standard.
13C NMR spectra were recorded at 50.3 MHz on a Bruker
AC-200 spectrometer. IR spectra were measured on a
Perkin–Elmer 1750 or Nicolet 510 FT-IR Spectrometer.
Mass spectra were measured with a Finnigan MAT (ITD)
800. The intermediates 12–15 were prepared as previously
described.10
3.2. 1b-Acetoxy-5a-hydroxy-4b,10b-dimethyl-7,7-
ethylenodioxy-decalin (16)
To a solution of the alcohol 15 (0.15 g, 0.59 mmol) in Et3N
(5 mL) was added Ac2O (1 mL), followed by DMAP (some
crystals) at room temperature. After stirring for 72 h the
reaction mixture was diluted with MeOH (10 mL). The mix-
ture was concentrated under reduced pressure and the resi-
due was quenched with diluted HCl and extracted with
AcOEt. The organic layer was washed with satd aq NaHCO3
and brine, dried over Na2SO4 and concentrated under re-
duced pressure. The residue was purified by silica gel chro-
matography (CHCl3/AcOEt, 7:3 as eluent), to give 16 as an
oil, which decomposes partially to the corresponding ketone
17, and therefore was used without further purification
(75%; 0.13 g, 0.44 mmol). 1H NMR d 5.06 (dd, J 7.8,
6.1 Hz, 1H), 4.27 (s, 1H), 3.93–3.79 (m, 4H), 2.05 (d,
J 14.0 Hz, 1H), 1.90 (s, 3H), 2.22–1.15 (m, 10H), 0.99
(s, 3H), 0.89 (s, 3H); 13C NMR d 170.4, 109.6, 76.9,
76.8, 64.1, 63.7, 41.1, 39.2, 38.8, 31.2, 30.4, 25.8, 22.6,
21.0, 16.2, 16.0; IR (film) nmax: 3431, 2931, 1730, 1247,
3.5. 1b-Acetoxy-4b,10b-dimethyl-5a-hydroxy-7a-
(10-hydroxy)-ethyl decalin (19a and 19b)
A solution of BH3$THF (1.0 M; 2.9 mL, 2.9 mmol) was
slowly added to a solution of 18 (0.19 g, 0.71 mmol) in
anhydrous THF (15 mL) at 0 ꢀC, under N2. The mixture was
stirred for 21 h at room temperature and then for 1 h at
reflux. The reaction mixture was cooled to 0 ꢀC, and a mix-
ture of NaOH 3 M (2 mL) and H2O2 30% (1.8 mL) was
added. After stirring for 15 h at room temperature, the mix-
ture was stirred for 1 h under reflux and then was allowed to
reach room temperature, when brine was added. The layers
were separated and the aqueous phase was then extracted
with CH2Cl2. The combined organic phases were concen-
trated under reduced pressure. The residue was purified by
silica gel chromatography (hexanes/AcOEt, 7:3 as eluent),
to give a 1:1 mixture of the diastereoisomeric diols 19a
and 19b (75%; 0.15 g, 0.53 mmol). Analytical samples
were obtained by further purification. 19a: 1H NMR
d 5.10 (dd, J 10.4, 5.8 Hz, 1H), 4.54 (br s, 2H), 3.90 (q,
J 6.4 Hz, 1H), 2.40 (dd, J 14.7, 7.9 Hz, 1H), 2.31–1.58
(m, 11H), 1.99 (s, 3H), 1.19 (d, J 6.4 Hz, 3H), 1.08 (s,
3H), 1.04 (d, J 7.7 Hz, 3H); 13C NMR d 171.0, 77.3, 75.8,
73.6, 41.0, 39.6, 38.1, 37.1, 31.5, 26.2, 22.8, 22.7, 21.2,
17.7, 17.2, 16.4; IR (film) nmax: 3367, 2931, 1714, 1248,
986 cmꢁ1
.
3.3. 1b-Acetoxy-4b,10b-dimethyl-5a-hydroxy-octal-7-
one (17)
A solution of 16 (0.53 g, 1.8 mmol) in AcOH (5 mL) was
stirred at 65 ꢀC for 20 min, and then cooled to 10 ꢀC,
when a satd solution of NaHCO3 was added. After extraction
with AcOEt, the organic layer was washed with brine, dried
over Na2SO4 and concentrated under reduced pressure. The
residue was purified by silica gel chromatography (hexanes/
AcOEt, 7:3 as eluent), affording 17 (94%; 0.42 g, 1.7 mmol)
as white crystals. Mp 184–185 ꢀC; 1H NMR d 5.12 (dd, J 8.0,
6.3 Hz, 1H), 2.90 (d, J 14.7 Hz, 1H), 2.85–1.32 (m, 11H),
2.00 (s, 3H), 1.27 (s, 3H), 1.06 (d, J 7.6 Hz, 3H); 13C
NMR d 211.9, 170.6, 80.5, 76.8, 50.0, 40.9, 40.6, 37.5,
33.9, 25.8, 22.6, 21.1, 17.2, 16.0; IR (film) nmax: 3405,
1083 cmꢁ1
.
1
19b: H NMR d 5.10 (dd, J 10.9, 5.4 Hz, 1H), 3.98 (q,
J 6.1 Hz, 1H), 3.41 (br s, 2H), 2.29–1.29 (m, 12H), 2.00
(s, 3H), 1.17 (d, J 6.2 Hz, 3H), 1.09 (s, 3H), 1.03 (d,
J 7.6 Hz, 3H); 13C NMR d 171.0, 77.1, 75.6, 70.9, 41.3,
39.8, 38.3, 30.5, 30.2, 26.2, 23.6, 22.8, 22.5, 21.2, 17.1,
16.3; IR (film) nmax: 3156, 2971, 2959, 1729, 1248 cmꢁ1
.

9236
H. M. C. Ferraz et al. / Tetrahedron 62 (2006) 9232–9236
Anal. Calcd for C16H28O4: C¼67.57%, H¼9.92%; Found:
67.30%, H¼10.13%.
3.6. 5-7(10)-Hemiacetal of 1b-acetoxy-4b,10b-dimethyl-
5a-hydroxy-7a-(10-oxo-10-methyl)-decalin (21)
3H), 1.96–1.32 (m, 9H), 1.75 (s, 3H), 1.24 (s, 3H), 1.19 (d,
J 7.5 Hz, 3H); 13C NMR d 215.8, 149.5, 108.9, 78.6, 51.2,
40.5, 39.3, 37.2, 34.2, 30.1, 27.9, 25.4, 21.1, 20.4, 17.7; IR
(film) nmax: 3430, 2959, 2927, 2859, 1692 cmꢁ1; MS (EI)
m/z (%) 236 (Mꢂ+, 10), 109 (100).
To a solution of 19a/19b (0.080 g, 0.28 mmol) in CH2Cl2
(10 mL), was added PCC (0.16 g, 0.74 mmol), followed by
anhydrous NaOAc (0.018 mg, 0.22 mmol). After stirring
for 3 h at room temperature, the reaction mixture was
quenched with water and diluted with CH2Cl2. The organic
layer was washed with NaHCO3 (5%) and brine, dried over
MgSO4 and concentrated under reduced pressure. The crude
product was chromatographed on silica gel (hexanes/AcOEt,
7:3 as eluent), to give 21 (64%; 0.051 g, 0.18 mmol). This
product showed to be very unstable and was employed in
the next step without any purification. 1H NMR d 4.92 (dd,
J 9.2, 6.7 Hz, 1H), 2.18–1.19 (m, 13H), 2.01 (s, 3H), 1.50
(s, 3H), 1.11 (s, 3H), 1.03 (d, J 7.5 Hz, 3H); 13C NMR
d 170.8, 104.7, 90.8, 79.8, 44.9, 42.4, 39.4, 36.0, 33.8,
27.0, 23.5, 22.4, 22.3, 21.2, 17.4, 16.7.
Acknowledgements
The authors are grateful to Prof. Mauricio G. Constantino,
for fruitful discussions, and to Profs. Nicola Petragnani,
Luiz F. Silva Jr and Tiago O. Vieira, for their valuable sug-
gestions and criticisms. We also thank FAPESP, CNPq and
CAPES for their generous financial support.
References and notes
1. Garbarino, J. A.; Gambaro, V.; Chamy, M. C. J. Nat. Prod.
1985, 48, 323.
2. Nyasse, B.; Tih, R. G.; Sondengam, B. L.; Martin, M. T.; Bodo,
B. Phytochemistry 1988, 27, 179.
3. Gordon-Gray, K. D.; Ward, C. J.; Edwards, T. J. S. Afr. J. Bot.
2006, 72, 147 and references cited therein.
3.7. Octahydro-4b,8ab-dimethyl-6b-(1-methylethenyl)-
1b,4aa-(2H)-naphthalenediol; corymbolol (2b)2
4. Zoghbi, M. G. B.; Andrade, E. H. A.; Oliveira, J.; Carreira,
L. M. M.; Guilhon, G. M. S. P. J. Essent. Oil Res. 2006, Jan/Feb.
5. Maxwell, N. Americas; Organization of American States:
Washington, DC, 1977; Vol. 29, portuguese version, p 2.
6. Garbarino, J. A.; Chamy, M. C.; Gambaro, V. Phytochemistry
1985, 24, 2726.
7. Ngo Bum, E.; Lingenhoehl, K.; Rakotonirina, A.; Olpe, H.-R.;
Schmutz, M.; Rakotonirina, S. J. Ethnopharmacol. 2004, 95,
303.
8. Duarte, M. C. T.; Figueira, G. M.; Sartoratto, A.; Rehder,
V. L. G.; Delarmelina, C. J. Ethnopharmacol. 2005, 97, 305.
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61, 147.
10. Souza, A. J. C.; Ferraz, H. M. C.; Tenius, B. S. M. Quim. Nova
1993, 16, 105.
To anhydrous DMSO (20 mL) under N2, n-BuLi (2.5 M in
hexane; 0.92 mL, 2.3 mmol) was added. After stirring for
30 min, methyl triphenylphosphonium bromide (0.82 g;
2.3 mmol) was added and the mixture was stirred for 1 h.
A solution of 21 (0.13 g; 0.46 mmol) in anhydrous DMSO
(5 mL) was added and the mixture was stirred for 7 h at
50 ꢀC. After this period the reaction mixture was quenched
with water (50 mL) and extracted with AcOEt, the organic
layer was washed with satd NaCl solution, dried over
Na2SO4 and concentrated under reduced pressure. The crude
product was chromatographed on silica gel (hexanes/AcOEt,
7:3 as eluent), to give 2b as an oil (74%; 0.081 g,
1
0.34 mmol). H NMR d 4.73 (s, 2H), 3.89 (dd, J 10.5,
5.9 Hz, 1H), 2.48–1.19 (m, 14H), 1.75 (s, 3H), 1.04 (d,
J 7.2 Hz, 3H), 1.02 (s, 3H); 13C NMR d 150.2, 108.5, 77.4,
74.1, 41.7, 41.1, 39.6, 38.3, 33.2, 26.7, 26.3, 25.9, 21.0,
16.7, 15.5; IR (film) nmax: 3422, 2941, 2867, 1456,
1011 cmꢁ1; MS (EI) m/z (%) 220 ([MꢁH2O]ꢂ+, 2), 109
(100).
11. Boyce, C. B. C.; Whitehurst, J. S. J. Chem. Soc. 1960, 2680.
12. Heathcock, C. H.; Ratcliffe, R. J. Am. Chem. Soc. 1971, 93,
1746.
13. Danishefsky, S. J.; Masters, J. J.; Young, W. B.; Link, J. T.;
Snyder, L. B.; Magee, T. V.; Jung, D. K.; Isaacs, R. C. A.;
Bornmann, W. G.; Alaimo, C. A.; Coburn, C. A.; Di Grandi,
M. J. J. Am. Chem. Soc. 1996, 118, 2843.
3.8. Octahydro-4aa-hydroxy-4b,8ab-dimethyl-6b-(1-
methylethenyl)-1(2H)-naphthalenone; corymbolone (1)1
14. Castellano, E. E.; Zukerman-Schpector, J.; Ferraz, H. M. C.;
Souza, A. J. C.; Tenius, B. S. M. Acta Crystallogr. 1992,
C48, 2080.
To a solution of 2b (0.040 g, 0.17 mmol) in CH2Cl2 (10 mL),
PCC (0.11 g, 0.51 mmol) was added. After stirring for 3 h at
room temperature, the reaction mixture was quenched with
water and diluted with CH2Cl2. The organic layer was
washed with NaHCO3 (5%) and brine, dried over MgSO4
and concentrated under reduced pressure. The crude product
was chromatographed on silica gel (hexanes/AcOEt, 7:3 as
15. Ferraz, H. M. C.; Muzzi, R. M.; Vieira, T. O.; Viertler, H.
Tetrahedron Lett. 2000, 41, 5021.
16. Kesselmans, R. P. W.; Wijnberg, J. B. P. A.; Minnaard, A. J.;
Walinga, R. E.; de Groot, A. J. Org. Chem. 1991, 56, 7237.
17. Fuhshuku, K.; Funa, N.; Akeboshi, T.; Ohta, H.; Hosomi, H.;
Ohba, S.; Sugai, T. J. Org. Chem. 2000, 65, 129 and references
cited therein.
1
eluent), to give 1 as an oil (76%; 0.031 g, 0.13 mmol). H
NMR d 4.74 (s, 2H), 2.72–2.60 (m, 1H), 2.48–2.33 (m,
18. Kasai, Y.; Shimanuki, K.; Kuwahara, S.; Watanabe, M.;
Harada, N. Chirality 2006, 18, 177.