Chiral decalins: Preparation from oleanolic acid and application in the synthesis of (-)-9-epi-ambrox

Article abstract of DOI:10.1021/np060159a

A novel and versatile process was developed to prepare the trans-decalins Δ⁹⁽¹¹⁾-3β-acetoxysclareolide (2) and Δ ⁹⁽¹¹⁾-3β-acetoxy-8-epi-sclareolide (3), respectively, with 4a-methoxycarbonyl-2,7,7-trimethyl-1-oxo-cis-decalin-2-ene (4

Full text of DOI:10.1021/np060159a

© Copyright 2006 by the American Chemical Society and the American Society of Pharmacognosy
Volume 69, Number 11
November 2006
Full Papers
Chiral Decalins: Preparation from Oleanolic Acid and Application in the Synthesis of
(-)-9-epi-Ambrox
Hai-Jun Yang,†,‡ Bo-Gang Li,† Xiao-Hua Cai,†,‡ Hua-Yi Qi,† Ying-Gang Luo,† and Guo-Lin Zhang*,†
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People’s Republic of China, and Graduate School of the
Chinese Academy of Sciences, Beijing 100039, People’s Republic of China
ReceiVed April 8, 2006
A novel and versatile process was developed to prepare the trans-decalins ∆9(11)-3â-acetoxysclareolide (2) and ∆9(11)
-
3â-acetoxy-8-epi-sclareolide (3), respectively, with 4a-methoxycarbonyl-2,7,7-trimethyl-1-oxo-cis-decalin-2-ene (4) and
its C-3 hydroxyl derivative 5 from oleanolic acid (3â-hydroxyolean-12-en-28-oic acid, 1). Three key steps were (a)
introduction of the AcO-12 group and the C-9,C-11 double bond at ring C of methyl 3â-acetoxyolean-12-en-28-oate (8)
to afford the diene, methyl 3,12-diacetoxyolean-9(11),12-dien-28-oate (11); (b) photolytic cleavage of the C-8,C-14
bond in the diene to give an acetoxy-substituted triene 14; and (c) oxidative cleavage of the triene or its hydrolyzed
R,â-unsaturated ketone product with m-CPBA/TsOH to give the cis- and trans-decalins 2-5. ∆9(11)-3â-Acetoxysclareolide
(2) was stereospecifically reduced to give 3â-acetoxy-9-epi-sclareolide (23), from which (-)-9-epi-ambrox (7) was
synthesized.
Decalin is one of the most prevalent structural units present in
natural products possessing diverse and significant biological
activities1 and olfactory and fixative properties.2 To date, numerous
syntheses of these kinds of compounds have been accomplished.1,3
Most of the syntheses are based on transformation of terpenes such
as sclareolide,4 abietic acid,5 labdanolic acid,6 sclareol,7 manool,8
larixol,9 and communic acid10 or well-established synthetic chiral
materials such as Wieland-Miescher ketone.11 Nevertheless, almost
all these semisynthetic materials are comparatively rare and
expensive, bear no functional groups on ring A (C-1 to C-4), possess
a Me-8â functionality, and may not be employed to synthesize
compounds with functional groups on ring A or those with a Me-
8R group. Thus, it would be highly advantageous to obtain chiral
decalins suitable for the versatile syntheses of these compounds
with or without functional groups on ring A and those with either
Me-8R or -8â substituents.
framework of the A/B rings, a 3â-hydroxy-4,4,8,10-tetramethyl-
trans-decalin, could be used as a versatile precursor for a large
number of natural products.1 In addition, the cis-decalin fragment
of the D/E rings could also be transformed into triterpenoids, such
as achilleol B13 and camelliols A and B.14 Thus, it would be of
importance to generate simultaneously cis- and trans-decalins
derived from the A/B and D/E fragments of 1 by cleavage of ring
C in a facile manner.
Ring C of 1 was converted into the triene G1, which could not
be directly cleaved with different oxidants. Indirectly, the C-11,C-
12 double bond in G2 was cleaved with RuCl3/NaIO4 to give G3
and G4 in a total yield of 30% from G1 (Scheme 1a).15 Compounds
G3 and G4 are unstable, and G3 possesses no chiral centers at
C-8 and C-9. The yield for the cleavage of the C-9,C-11 bond is
even poorer with low selectivity.15 To date, there have been no
examples reported concerning the cleavage of the C-12,C-13 bond.
Enol acetates can be transformed into ketols or R-acetoxy ketones
via enol acetate epoxide16 or hydrolyzed to ketones and then they
might undergo a Baeyer-Villiger reaction with peracids. It was
presumed that AcO-11 or AcO-12 trienes could thus be easily
cleaved and the cleavage of the C-9,C-11, C-11,C-12, or C-12,C-
13 bonds could probably be selectively realized. In this study, we
have explored a route to cleave ring C of 1, which involves
Oleanolic acid (3â-hydroxyolean-12-en-28-oic acid, 1), a pen-
tacyclic triterpene, is abundant as a natural resource.12 Both the
A/B and D/E rings of 1 constitute decalin ring systems. The
* To whom correspondence should be addressed. Tel/Fax: +86-28-
85225401. E-mail: zhanggl@cib.ac.cn.
† Chengdu Institute of Biology, Chinese Academy of Sciences.
‡ Graduate School of the Chinese Academy of Sciences, Beijing.
10.1021/np060159a CCC: $33.50
© 2006 American Chemical Society and American Society of Pharmacognosy
Published on Web 10/21/2006

1532 Journal of Natural Products, 2006, Vol. 69, No. 11
Yang et al.
Scheme 1. Key Steps of Ring C Cleavage of Oleanolic Acid
Chart 1. Ring C Cleaved Products 2-5 of Oleanolic Acid, (-)-Ambrox (6), and (-)-9-epi-Ambrox (7)
Scheme 2. Synthesis of Acetoxy-Substituted Dienesa
a Reagents and conditions: (a) (i) Ac2O, pyridine, CHCl3, reflux; (ii) CH2N2, THF, 0f5 °C, 81%; (b) O3, CHCl3, then BF3‚Et2O, -5f0 °C, 85% or H2O2/HCOOH,
CHCl3, rt, 82%; (c) Br2, HBr in CH3COOH (33%) (cat.), CH3COOH, rt, 92%; (d) Ac2O, H2SO4/TsOH (cat.), rt, 87%; (e) CrO3‚2pyridine, CH2Cl2, 65%; (f) Ac2O,
H2SO4/TsOH (cat.), 80 °C, 46%.
oxidative cleavage of the acetoxy-substituted trienes II or their
hydrolyzed dienone products III (Scheme 1b). Cleavage of the
AcO-12 triene or its hydrolyzed product was carried out, and
selective access was realized to the trans-decalin ∆9(11)-3â-
acetoxysclareolide (2) or its 8-epimer, ∆9(11)-3â-acetoxy-8-epi-
sclareolide (3), respectively, with cis-decalins 4 and 5 (Chart 1).
conditions.2a,19 In this study, (-)-9-epi-ambrox (7) was synthesized
starting from ∆9(11)-3â-acetoxysclareolide (2).
Results and Discussion
Cleavage of Ring C of Oleanolic Acid (1). The R,â-unsaturated
ketone 10 was prepared via oxidation of 820 with H2O2/HCOOH
or O321 and then dehydrogenation with Br2/HBr22 in acetic acid. In
the enol acetylation of 10 with Ac2O, different catalysts such as
H2SO4/TsOH,23 PPA, CF3COOH, pyridine,24 and CH3COONa24b,25
were tested. It was found that H2SO4/TsOH was effective, and the
enol acetate 11 was obtained in 87% yield (Scheme 2), whereas
long reaction times were needed and low conversion rates were
obtained when pyridine or CH3COONa was used. When synthesiz-
ing the enol acetate of the ∆12-11-oxo compound 12,26 no reaction
occurred when pyridine and CH3COONa were used and a very low
As one of the most valuable animal perfumes, ambergris
possesses unique olfactive and fixative properties,2b which is related
principally to the presence of (-)-ambrox (6) (Chart 1). To date,
several syntheses of 6 have been reported.17 Studies on the
configuration-odor relationship revealed that (-)-9-epi-ambrox
(7)2a,b,18 possesses the strongest scent and lowest threshold con-
centration (0.15 ppb) among all stereoisomers of (-)-ambrox (6).
However synthetic methods of compound 7 are few and need to
be improved in view of long reaction routes, low yields, or rigorous

Chiral Decalins
Journal of Natural Products, 2006, Vol. 69, No. 11 1533
Scheme 3. Photochemical Ring Opening of Acetoxy-Substituted
Diene 11a
Figure 1. ORTEP diagram of triene 14.
a Reagents and conditions: (a) hV (high-pressure mercury lamp), Pyrex,
CH3COOEt, rt, 94%; (b) hV (high-pressure mercury lamp), quartz, CH3COOEt,
rt, 49% (14) and 35% (15); (c) (i) KOH, CH3OH, H2O, rt, (ii) Ac2O, pyridine,
91%; (d) (i) KOH, CH3OH, H2O, rt, (ii) Ac2O, pyridine, 87%.
Villiger reaction with peracids; thus, m-CPBA was chosen for the
cleavage of compound 14 (Scheme 4). Oxidation of 14 with
m-CPBA in the presence of NaHCO3 or phosphate buffer (pH 7.5)
gave epoxide 17 or 18 as the major product without triene cleavage.
Direct oxidation of 14 with m-CPBA gave compounds 2, 4, 5, and
diepoxide 18, as well as lactone 19. Compound 19 was the major
product when 14 was oxidized with H2O2/HCOOH at 50 °C. The
configurations of 2, 17, and 19 were confirmed by X-ray crystal-
lographic analysis.30 The triene cleaved products 2, 4, and 5 were
detected even if 14 was oxidized directly with less than 1 molar
equiv of m-CPBA. On the basis of products from oxidation of 14
with m-CPBA or m-CPBA and NaHCO3, the triene cleavage is
presumed to be an acid-catalyzed process. Different acids including
TsOH, H2SO4, and CF3COOH were tested. It was found that a
catalytic amount of TsOH could largely inhibit the production of
diepoxide 18 and lactone 19 and obviously improve the reaction.
Other oxidants such as H2O2/CH3COOH and t-BuOOH gave no
satisfactory results. Here, the introduction of an acetoxy group at
C-12 and application of m-CPBA/TsOH made cleavage of the
C-12,C-13 bond of the triene facile and selective. At the same time,
oxidation of (8Z,11Z,13E)-triene 15 with m-CPBA/TsOH rendered
the same products 2, 4, and 5 (Scheme 4).
conversion rate was observed when H2SO4/TsOH was employed
at room temperature. Using H2SO4/TsOH as catalyst at 80 °C, ring
A was transformed into a five-membered ring and the double bond
was rearranged to give 13 (Scheme 2). A similar example using
PCl5 has also been documented.27
In ring C of 11, the conjugated double bonds and trans-
disposition between Me-8â and Me-14R allowed a six-electron-
system antarafacial reaction,28 which led to the cleavage of the bond
between C-8 and C-14 (Scheme 3). Irradiation of 11 in CH3COOEt
in a Pyrex flask under argon using a 500 W high-pressure Hg lamp
gave the (8Z,11E,13E)-triene 14 in 94% yield. The ring C opening
took place by a conrotatory photochemical electrocyclic reaction
similar to that evident in the transformation of ergosterol to
previtamin D.29 This process could be accomplished in different
solvents such as CH2Cl2, CHCl3, and EtOH. Interestingly, when
11 was irradiated in a quartz flask, 14 and its isomer (8Z,11Z,-
13E)-triene 15 were obtained in 49% and 35% yields, respectively.
The two isomers could interconvert when irradiated in a quartz
flask, indicating that compound 15 is a further photochemical
product of 14. The different results in Pyrex and quartz flasks are
probably due to the light of different wavelengths allowed to
penetrate. In fact, both compounds are unstable when irradiated in
a quartz flask, and thus long reaction times should be avoided to
prevent further reactions.
Significantly, oxidation of 16 with m-CPBA/TsOH gave 3, an
8-epimer of 2, and 2, 4, and 5 (Scheme 5). The ratio of 3/2 was
1
5:1, as determined from the H NMR spectrum. Slow recrystalli-
zation of the mixture of 3 and 2 from n-hexane/acetone (8:1) gave
crystals with two different shapes, which could be manually
separated to give pure 3 and 2. Similar to 14, compound 16 was
oxidized with m-CPBA in the presence of NaHCO3 to give epoxide
20 or 21. The configurations of 3 and 21 were determined by X-ray
crystallographic analysis.30
Compounds 2 and 3 possess a 3â-acetoxy-4,4,8,10-tetramethyl-
trans-decalin system and consequently are versatile synthons for
the syntheses of natural products with Me-8R or -8â groups and
with or without functional groups on ring A. Compounds 4 and 5,
with a cis-decalin framework, are also important intermediates for
the syntheses of tricyclic triterpenoids, such as achilleol B13 and
camelliols A and B.14
The spectroscopic data of 14 and 15 did not provide conclusive
evidence for their configurations. X-ray crystallographic analysis
of 14 confirmed the configuration of 14 as a (8Z,11E,13E)-triene
(Figure 1).30 Acetylation of the hydrolyzed products of 14 or 15
with Ac2O gave the same product, 16 (Scheme 3), and thus, the
structure of compound 15 was indirectly established as a (8Z,11Z,-
13E)-triene.
A [1,7]H sigmatropic shift in the transformation of provitamin
29
D2 to vitamin D2 and a [1,5]H sigmatropic migration of a
triterpenoid cis-triene15 have been reported. However, no H
sigmatropic shift reactions occurred when compound 14 or 15 was
irradiated with ultraviolet light. It is probably because the serious
distortion of these molecules as shown from the crystal structure
of 14 (Figure 1) destroys the conjugations of the trienes and prevents
the molecules from any antarafacial or suprafacial [1,7]H or [1,5]H
sigmatropic migration. The unconjugated triene is also revealed by
the fact that 14 possesses no ultraviolet absorption in the region of
a normal conjugated triene.
Synthesis of (-)-9-epi-Ambrox (7) from 2. Compound 2
possesses substitution patterns and configurations similar to those
of (-)-9-epi-ambrox (7) and could be used as a starting material
for the synthesis of 7 (Scheme 6). The key step for the synthesis
of 7 from 2 was to reduce the C-9,C-11 double bond stereospe-
cifically. Unsaturated lactone 2 was reduced with Mg in CH3OH
1
to give 22. The H NMR and 13C NMR data of 22 were quite
The oxidation of compound 14 with KMnO4, KMnO4/NaIO4,
or O3 gave complex mixtures. Enol acetates can be transformed
into ketols or R-acetoxy ketones via enol acetate epoxides16 or
hydrolyzed to ketones, and then they might undergo a Baeyer-
different from those of 3â-hydroxysclareolide.31 Acetylation of 22
with Ac2O gave the product 23, which could also be obtained
directly from 2 in high yields by reduction with NaBH4/NiCl2‚
6H2O32 or by hydrogenation with H2 in the presence of 10% Pd/C.

1534 Journal of Natural Products, 2006, Vol. 69, No. 11
Scheme 4. Oxidation of Trienes 14 and 15a
Yang et al.
a Reagents and conditions: (a) m-CPBA (1 equiv), NaHCO3, CH2Cl2, rt, 74%; (b) m-CPBA (2 equiv), NaHCO3, CH2Cl2, rt, 56%; (c) m-CPBA (1 equiv), NaHCO3,
CH2Cl2, rt, 71%; (d) m-CPBA(3 equiv), CH2Cl2, rt, 51% (2), 23% (4), 22% (5), 8% (18), and 16% (19); (e) H2O2/HCOOH, CHCl3, 50 °C, 60%; (f) m-CPBA(3 equiv),
TsOH (cat.), CH2Cl2, rt, 82% (2), 57% (4), and 8% (5); (g) m-CPBA(3 equiv), TsOH (cat.), CH2Cl2, rt, 76% (2), 52% (4), and 10% (5).
Scheme 5. Oxidation of Dienone 16a
on the introduction of an AcO-12 group and a C-9,C-11 double
bond at ring C of methyl 3-acetoxyolean-12-en-28-oate (8),
photolytic cleavage of the C-8,C-14 bond in the resulting diene,
methyl 3,12-diacetoxyolean-9(11),12-dien-28-oate (11), and oxida-
tive cleavage of the resulting acetoxy-substituted triene 14 or its
hydrolyzed product 16, with a novel method using m-CPBA/TsOH.
All of the decalins, especially the trans ones, are useful and versatile
precursors for the syntheses of important natural products possessing
a decalin framework, with Me-8R or Me-8â groups and with or
without functional groups on ring A. The stereospecific reduction
of ∆9(11)-3â-acetoxysclareolide (2) gave 3â-acetoxy-9-epi-sclar-
eolide (23). Compound 23, an important synthon with 9S config-
uration, is difficult to prepare from other natural compounds. From
23, (-)-9-epi-ambrox (7) was synthesized.
Experimental Section
General Experimental Procedures. Melting points were determined
with an X-6 melting point apparatus and are uncorrected. Optical
rotations were measured on a Perkin-Elmer 341 automatic polarimeter.
UV and IR spectra were obtained on a Lambda 35 spectrometer and a
Perkin-Elmer FT-IR spectrometer, respectively. NMR spectra were
recorded on a Bruker Advance 600 spectrometer with TMS as internal
standard. Electrospray ionization mass spectra (ESIMS) were acquired
on a Finnigan LCQDECA mass spectrometer, and electron ionization mass
spectra (EIMS) were recorded on a VG7070E mass spectrometer.
HRESIMS were carried out on a BioTOF-Q mass spectrometer. Silica
gel (200-300 mesh) was used for column chromatography. Precoated
plates (silica gel GF254, 0-40 µm) activated at 110 °C for 2 h were
used for TLC detected with an UV lamp, I2, and an 8% ethanol solution
of phosphomolybolic acid or a 5% ethanol solution of H2SO4.
Commercial reagents were used without purification. All solvents
including petroleum ether (60-90 °C) were distilled prior to use.
Anhydrous THF was distilled from Na and benzophenone.
a Reagents and conditions: (a) m-CPBA (3 equiv), TsOH (cat.), CH2Cl2, rt,
69% (3 + 2, 3/2 ) 5:1), 49% (4) and 7% (5); (b) m-CPBA (1 equiv), NaHCO3,
CH2Cl2, rt, 84%; (c) m-CPBA (2 equiv), NaHCO3, CH2Cl2, rt, 45%; (d) m-CPBA
(1 equiv), NaHCO3, CH2Cl2, rt, 57%.
The X-ray crystallographic analysis of 23 suggested that 22 is 3â-
hydroxy-9-epi-sclareolide.30
Reductive removal of a sulfonate group with LAH can transform
sulfonate to the corresponding hydrocarbon.33 However, reduction
of sulfonate 24 or 25 with LAH in THF and then cyclization with
TsOH‚H2O34 in CH3NO2 did not afford the target compound 7 but
its 3â-hydroxylated derivative, 3â-hydroxy-9-epi-ambrox (26).
Cleavage of the S-O bond occurred probably because the C-O
bond of the sulfonate was sterically hindered.35 At the same time,
compound 26 was also obtained via reduction of 23 with LAH in
THF and then cyclization with TsOH‚H2O in CH3NO2. The
configuration of 26 was confirmed by X-ray crystallographic
analysis.30
Compound 26 was mesylated with methanesulfonyl chloride to
give the mesylate 27 in 93% yield (Scheme 6). Then, Zn/NaI35
was used to reductively remove the mesyloxy group in dimethoxy-
ethane (DME) under reflux, but a mixture of (-)-9-epi-ambrox (7),
28, and 29 was obtained. However, removal of the mesyloxy group
in 27 with LiCl in DMF at 100 °C rendered the alkene 28 in 80%
yield. Hydrogenation of 28 gave the target compound 7 quantita-
tively.
Methyl 3,12-Diacetoxyolean-9(11),12-dien-28-oate (11). To a
solution of compound 10 (1 g, 1.9 mmol) in acetic anhydride (10 mL)
were added a drop of concentrated H2SO4 and a catalytic amount of
TsOH (20 mg). The reddish reaction mixture was stirred at room
temperature for 5 h and then poured into a mixture of ice/water. The
solid precipitate was filtered, washed with saturated aqueous NaHCO3
and water, dried, and purified over a silica gel column (eluted by
petroleum ether/AcOEt, 20:1) to render 11 (0.939 g, 87%). Compound
11 (colorless cubic crystals): mp 165.8-167.9 °C; [R]20 +194.4
D
(c 0.29, CHCl3); UV (MeOH) λmax (log ꢀ) 278 (3.96) nm; IR (KBr)
ν
max 2946, 2867, 1729, 1656, 1240 cm-1; 1H NMR (CDCl3, 600 MHz)
An efficient and convenient process was developed to prepare
δ 5.40 (1H, s, H-11), 4.51 (1H, dd, J ) 11.6, 4.7 Hz, H-3), 3.63 (3H,
s, -COOCH3), 3.22 (1H, dd, J ) 13.3, 3.8 Hz, H-18), 2.16 (3H, s,
CH3COO-12), 2.06 (3H, s, CH3COO-3), 1.22, 1.07, 1.06, 0.95, 0.92,
0.90, 0.87 (each 3H, s, Me); 13C NMR (CDCl3, 150 MHz) δ 177.9,
171.0, 169.2, 156.5, 140.8, 129.0, 114.9, 80.4, 51.7, 51.0, 45.3, 43.0,
the trans-decalin ∆9(11)-3â-acetoxysclareolide (2) or its 8-epimer,
∆
9(11)-3â-acetoxy-8-epi-sclareolide (3), respectively, with 4a-meth-
oxycarbonyl-2,7,7-trimethyl-1-oxo-cis-decalin-2-ene (4) and its C-3
hydroxyl derivative 5 from oleanolic acid (1). This process relies

Chiral Decalins
Journal of Natural Products, 2006, Vol. 69, No. 11 1535
Scheme 6. Synthesis of (-)-9-epi-Ambrox (7)a
a Reagents and conditions: (a) Mg, CH3OH, reflux, 74%; (b) Ac2O, pyridine, CH2Cl2, rt, 95%; (c) MsCl or TsCl, pyridine, 0 °C, 96% (24) and 78% (25); (d) (i)
LAH, THF, N2, reflux, (ii) TsOH‚H2O, CH3NO2, 73% from 24; (e) NaBH4, NiCl2‚6H2O, MeOH, 0 °C to rt, 97%; (f) (i) LAH, LiCl, THF, N2, reflux, (ii) TsOH‚H2O,
CH3NO2, 77%; (g) MsCl, pyridine, 0 °C, 93%; (h) Zn, NaI, DME, reflux, 42% (28), 14% (29), and 28% (7); (i) LiCl, DMF, 100 °C, 80%; (j) 10% Pd/C, H2 (4 MPa),
100%.
41.4, 40.4, 38.8, 37.9, 36.7, 33.8, 32.8, 32.7, 32.1, 32.0, 30.5, 28.1,
27.0, 25.0, 24.1, 23.4, 23.3, 21.3, 20.7, 20.2, 20.0, 18.0, 16.7; ESIMS
m/z 1158.9 [2M + Na]+ (64), 591.3 [M + Na]+ (100); HRESIMS m/z
[M + Na]+ 591.3665 (calcd for C35H52NaO6, 591.3656).
(KBr) νmax 2956, 1736, 1719, 1685, 1628, 1243 cm-1; 1H NMR (CDCl3,
600 MHz) δ 4.53 (1H, dd, J ) 11.7, 4.6 Hz, H-3), 3.71 (3H, s,
-COOCH3), 3.47 and 3.19 (each 1H, d, J ) 19.0 Hz, H-11), 3.08
(1H, dd, J ) 12.9, 3.2 Hz, H-18), 2.05 (3H, s, CH3COO-), 1.62 (3H,
s, H-27), 1.44 (3H, s, H-26), 0.96 (3H, s, Me), 0.92 (3H, s, Me), 0.90
(6H, s, Me), 0.88 (3H, s, Me); 13C NMR (CDCl3, 150 MHz) δ 204.9,
177.8, 170.8, 139.0, 133.0, 132.9, 129.8, 80.6, 51.8, 50.3, 44.9, 42.2,
39.9, 37.9, 37.7, 34.2, 34.1, 33.7, 33.4, 32.5, 31.8, 30.6, 29.9, 28.0,
23.9, 23.8, 22.6, 21.3, 20.4, 20.0, 19.9, 18.6, 16.6; ESIMS m/z 565.3
[M + K]+ (2), 549.4 [M + Na]+ (100), 489.3 (26); HRESIMS m/z [M
+ Na]+ 549.3527 (calcd for C33H50NaO5, 549.3550).
Methyl 3,12-Diacetoxy-8,14-seco-olean-8Z,11E,13E-trien-28-oate
(14). A solution of compound 11 (100 mg) in ethyl acetate (20 mL) in
a Pyrex flask under argon was irradiated using a 500 W high-pressure
Hg lamp at room temperature until compound 11 disappeared (moni-
tored by TLC). Then, the solvent was evaporated under reduced pressure
to give a syrup, which was purified over a silica gel column (petroleum
ether/AcOEt, 25:1) to afford 14 (94 mg, 94%) as a colorless oil. An
oily solution of 14 in a small amount of petroleum ether/AcOEt (25:1)
stood for several days, and colorless cubic crystals were obtained.
∆
9(11)-3â-Acetoxysclareolide (2), cis-Decalin 4, and cis-Decalin 5.
(1) Starting from 14: To a solution of 14 (100 mg, 0.18 mmol) in
CH2Cl2 (10 mL) were added a catalytic amount of TsOH and then
m-CPBA (75%) (120 mg, 0.52 mmol). The reaction mixture was stirred
for 12 h at room temperature. The resulting solution was washed with
saturated aqueous NaHSO3, saturated aqueous NaHCO3, and brine, dried
over MgSO4, filtered, and evaporated to dryness. The residue was
separated over a silica gel column (petroleum ether/AcOEt, 25:1, and
then petroleum ether/AcOEt, 4:1) to afford compounds 2 (44 mg, 82%),
4 (25 mg, 57%), and 5 (4 mg, 8%).
Compound 14 (colorless cubic crystals): mp 128.5-129.7 °C; [R]20
D
+170.6 (c 0.14, CHCl3); IR (KBr) νmax 2946, 2863, 1732, 1455, 1366,
1
1247, 1207, 1027 cm-1; H NMR (CDCl3, 600 MHz) δ 5.78 (1H, s,
H-11), 4.54 (1H, dd, J ) 11.2, 3.7 Hz, H-3), 3.65 (3H, s, -COOCH3),
2.86 (1H, br s), 2.10 and 2.07 (each 3H, s, CH3COO-3 and CH3COO-
12), 1.62 and 1.60 (each 3H, s, H-26 and H-27), 0.91 (6H, s, Me),
0.90 (3H, s, Me), 0.88 (6H, s, Me); 13C NMR (CDCl3, 150 MHz) δ
178.0, 171.0, 169.0, 147.1, 134.2, 133.3, 132.6, 132.0, 119.0, 80.8,
51.7, 51.2, 44.9, 41.9, 38.8, 37.8, 36.6, 35.4, 34.9, 33.9, 33.0, 30.6,
29.9, 28.2, 24.6, 24.3, 22.3, 22.1, 21.9, 21.6, 21.4, 18.6, 16.7; ESIMS
m/z 607.4 [M + K]+ (5), 591.3 [M + Na]+ (100), 568.5 [M + H]+
(3), 509.2 [M + H - CH3COOH]+ (17), 449.3 (26); HRESIMS m/z
[M + Na]+ 591.3642 (calcd for C35H52NaO6, 591.3656).
Methyl 3â-Acetoxy-12-oxo-8,14-seco-olean-8Z,13E-dien-28-oate
(16). (1) Starting from 14: To a solution of compound 14 (100 mg,
0.18 mmol) in methanol (5 mL) were added KOH (15 mg, 0.27 mmol)
and water (0.2 mL). The reaction mixture was stirred at room
temperature for 12 h. Then, water (20 mL) was added and the mixture
was extracted with CH2Cl2 three times. The combined organic layer
was washed with water and brine and dried over MgSO4. After removal
of the MgSO4 via filtration, pyridine (0.5 mL) and acetic anhydride
(0.2 mL) were added directly. The resulting solution was stirred at room
temperature for 5 h and then washed with water, 5% HCl(aq), saturated
aqueous NaHCO3, and brine, dried over MgSO4, and filtered. Then,
the solvent was evaporated under reduced pressure to give a residue,
which was purified over a silica gel column (petroleum ether/AcOEt,
25:1) to afford compound 16 (84 mg, 91%).
(2) Starting from 15 with the same procedure as (1): 2 (75%), 4
(52%), and 5 (10%).
Compound 2: colorless cubic crystals; mp 171.1-171.9 °C; [R]20
D
-118.8 (c 0.14, CHCl3); UV (MeOH) λmax (log ꢀ) 215 (4.12) nm; IR
(KBr) νmax 3006, 2982, 2955, 2932, 2864, 1757, 1731, 1628, 1374,
1
1254, 1027, 955 cm-1; H NMR (CDCl3, 600 MHz) δ 5.56 (1H, s,
H-11), 4.50 (1H, dd, J ) 10.9, 4.5 Hz, H-3), 2.33 (1H, dt, J ) 12.1,
2.8 Hz, H-7), 2.09 (3H, s, CH3COO-), 1.84-1.91 (3H, m, H-1, H-2
and H-6), 1.76-1.82 (2H, m, H-1 and H-2), 1.59 (1H, m, H-6), 1.58
(3H, s, H-16), 1.52 (1H, dt, J ) 12.8, 3.7 Hz, H-7), 1.24 (3H, s, H-15),
1.04 (1H, dd, J ) 12.1, 2.3 Hz, H-5), 0.98 (3H, s, H-14), 0.92 (3H, s,
H-13); 13C NMR (CDCl3, 150 MHz) δ 183.3 (C-9), 172.0 (C-12), 170.7
(CH3COO-), 109.9 (C-11), 86.9 (C-8), 79.5 (C-3), 54.7 (C-5), 40.4
(C-7), 39.3 (C-10), 38.5 (C-4), 34.9 (C-1), 28.1 (C-13), 25.3 (C-16),
23.2 (C-2), 21.1 (CH3COO-), 19.2 (C-6), 18.2 (C-15), 16.6 (C-14);
ESIMS m/z 329.2 [M + Na]+ (63), 307.2 [M + H]+ (100); HRESIMS
m/z [M + Na]+ 329.1726 (calcd for C18H26NaO4, 329.1723).
Compound 4: white amorphous powder; [R]20 +8.3 (c 0.05,
D
AcOEt), [R]20578 +10.4 (c 0.05, AcOEt), [R]20546 +8.3 (c 0.05, AcOEt),
(2) Starting from 15 with the same procedure as (1), yield: 87%.
[R]20 -50.0 (c 0.05, AcOEt), [R]20 -547.9 (c 0.05, AcOEt); UV
436
365
Compound 16: colorless cubic crystals; mp 145.6-146.7 °C; [R]20
(MeOH) λmax (log ꢀ) 236 (3.84) nm; IR (KBr) νmax 2951, 2864, 1731,
D
1
+159.2 (c 0.25, CHCl3); UV (MeOH) λmax (log ꢀ) 244 (3.74) nm; IR
1673, 1453, 1255, 1200, 1169 cm-1; H NMR (CDCl3, 600 MHz) δ

1536 Journal of Natural Products, 2006, Vol. 69, No. 11
Yang et al.
6.60 (1H, d, J ) 5.5 Hz, H-3), 3.65 (3H, s, -COOCH3), 3.02 (1H, dd,
J ) 13.6, 4.2 Hz, H-8a), 2.69 (1H, dt, J ) 18.7, 2.1 Hz, H-4), 2.56
(1H, dd, J ) 18.7, 5.9 Hz, H-4), 1.74 (3H, s, H-9), 1.70 (1H, dd, J )
13.7, 4.6 Hz, H-5), 1.63 (1H, dt, J ) 13.7, 3.5 Hz, H-5), 1.46 (1H, dd,
J ) 13.8, 4.4 Hz, H-6), 1.42 (1H, m, H-8), 1.36 (1H, m, H-6), 1.26
10), 32.6 (C-11), 28.3 (C-13), 27.3 (C-16), 26.8 (C-2), 22.9 (C-15),
19.0 (C-6), 15.7 (C-14); ESIMS m/z 305.4 [M + K]+ (30), 289.4 [M
+ Na]+ (100); HRESIMS m/z [M + Na]+ 289.1778 (calcd for C16H26-
NaO3, 289.1774).
3â-Acetoxy-9-epi-sclareolide (23). (1) Starting from 2: NaBH4 (32
mg, 0.8 mmol) at 0 °C was added under stirring to a solution of 2 (55
mg, 0.18 mmol) and NiCl2‚6H2O (10 mg, 0.05 mmol) in MeOH (20
mL). The mixture was stirred for 1 h at 0 °C and then 2 h at room
temperature, quenched with saturated aqueous NH4Cl, and extracted
with AcOEt. The combined organic layer was washed with brine, dried
over MgSO4, and filtered. Concentration of the filtrate in vacuo followed
by flash chromatography (petroleum ether/AcOEt 4:1) afforded 23 (54
mg, 97%).
(2) Starting from 2: To a stainless steel autoclave of 20 mL were
added a solution of compound 2 (50 mg) in ethyl acetate (5 mL) and
10% Pd/C (10 mg). The autoclave was evacuated and purged with
hydrogen three times, and then the pressure of hydrogen was kept at 4
MPa. The reaction mixture was stirred at room temperature for 24 h.
Then, stirring was stopped and the autoclave was vented slowly.
Removal of the Pd/C by filtration and concentration in vacuo gave 23
quantitatively.
(3) Starting from 22: To a solution of 22 (20 mg, 0.08 mmol) in
pyridine (2 mL) was added acetic anhydride (0.2 mL). The reaction
mixture was stirred at room temperature for 5 h, poured into water,
and extracted with ethyl acetate. The combined extracts were washed
with 5% HCl(aq), water, saturated aqueous NaHCO3, and brine, dried
over MgSO4, and filtered. Concentration of the filtrate in vacuo followed
by flash chromatography (petroleum ether/AcOEt 4:1) afforded 23 (22
mg, 95%).
(1H, t, J ) 13.5 Hz, H-8), 0.99, 0.96 (each 3H, s, H-11 and H-12); 13
C
NMR (CDCl3, 150 MHz) δ 201.1 (C-1), 177.2 (C-10), 141.8 (C-3),
134.4 (C-2), 52.4 (-COOCH3), 47.9 (C-4a), 46.1 (C-8a), 38.3 (C-8),
34.4 (C-6), 32.5 (C-11 or 12), 29.7 (C-5), 29.6 (C-7), 27.8 (C-4), 24.2
(C-11 or 12), 16.0 (C-9); ESIMS m/z 289 [M + K]+ (2), 251 [M +
H]+ (100), 191.1 [M + H - HCOOCH3]+ (94); HRESIMS m/z [M +
Na]+ 273.1457 (calcd for C15H22NaO3, 273.1461).
Compound 5: white amorphous powder; [R]20 -43.7 (c 0.05,
D
AcOEt), [R]20578 -45.8 (c 0.05, AcOEt), [R]20546 -56.3 (c 0.05, AcOEt),
[R]20436 -160.4 (c 0.05, AcOEt), [R]20365 -718.7 (c 0.05, AcOEt); UV
(MeOH) λmax (log ꢀ) 244 (4.03) nm; IR (KBr) νmax 3438, 2953, 2920,
1
1728, 1668, 1628, 1291, 1203 cm-1; H NMR (CDCl3, 600 MHz) δ
3.68 (3H, s, -COOCH3), 3.10 (1H, br d, J ) 18.5 Hz, H-4), 3.06 (1H,
dd, J ) 13.7, 4.4 Hz, H-8a), 2.93 (1H, d, J ) 18.5 Hz, H-4), 1.87 (3H,
s, H-9), 1.76 (1H, dt, J ) 13.7, 4.8 Hz, H-5), 1.64 (1H, dt, J ) 14.3,
3.4 Hz, H-5), 1.46 (1H, m, H-8), 1.42 (1H, dd, J ) 13.3, 4.2 Hz, H-6),
1.38 (1H, m, H-6), 1.25 (1H, t, J ) 13.5 Hz, H-8), 0.99, 0.97 (each
3H, s, H-11 and H-12); 13C NMR (CDCl3, 150 MHz) δ 198.0 (C-1),
176.2 (C-10), 150.0 (C-3), 132.0 (C-2), 52.6 (-COOCH3), 46.9 (C-
4a), 45.4 (C-8a), 38.3 (C-8), 36.3 (C-4), 34.2 (C-6), 32.4 (C-11 or 12),
29.7 (C-7), 29.3 (C-5), 24.1 (C-11 or 12), 12.4 (C-9); ESIMS m/z 265.6
[M - H]- (100); HRESIMS m/z [M - H]- 265.1450 (calcd for
C15H21O4, 265.1434).
∆
9(11)-3â-Acetoxy-8-epi-sclareolide (3). To a solution of 16 (82 mg,
0.16 mmol) in CH2Cl2 (5 mL) were added a catalytic amount of TsOH
and then m-CPBA(75%) (110 mg, 0.48 mmol). The reaction mixture
was stirred for 12 h at room temperature. The resulting solution was
washed with saturated aqueous NaHSO3, saturated aqueous NaHCO3,
and brine, dried over MgSO4, filtered, and concentrated in vacuo. The
residue was separated over a silica gel column (petroleum ether/AcOEt,
25:1, and then petroleum ether/AcOEt, 4:1) to afford a mixture of
compounds 3 and 2 (ratio of 3/2 ) 5:1) (33 mg, 69%), 4 (19 mg, 49%),
and 5 (3 mg, 7%). Slow recrystallization of the mixture of 3 and 2
from n-hexane/acetone (8:1) gave different crystal shapes, which could
be manually separated to give pure 3 as colorless needle crystals and
2 as colorless cubic crystals. Compound 3 (colorless needle crystals):
Compound 23: colorless cubic crystals; mp 189.2-189.8 °C; [R]20
D
-35.9 (c 0.20, CH3OH), [R]20578 -33.8 (c 0.20, CH3OH), [R]20546 -39.5
(c 0.20, CH3OH), [R]20 -71.3 (c 0.20, CH3OH), [R]20 -116.4 (c
436
365
0.20, CH3OH); IR (KBr) νmax 2982, 2951, 1769, 1756, 1726, 1627,
1267, 1245, 1025, 942 cm-1; 1H NMR (CDCl3, 600 MHz) δ 4.47 (1H,
dd, J ) 11.5, 5.1 Hz, H-3), 2.58 (1H, dd, J ) 17.2, 13.6 Hz, H-11),
2.43 (1H, dd, J ) 17.2, 8.2 Hz, H-11), 2.07 (3H, s, CH3COO-), 2.02-
2.08 (2H, m), 1.65-1.72 (3H, m), 1.59 (1H, m, H-7), 1.57 (3H, s,
H-16), 1.30-1.39 (3H, m), 1.21 (1H, dd, J ) 12.2, 1.8 Hz), 1.15, 0.93
and 0.88 (each 3H, s, Me); 13C NMR (CDCl3, 150 MHz) δ 175.1, 170.8,
85.6, 80.1, 56.5, 45.8, 37.3, 3.67, 35.7, 35.6, 32.5, 28.3, 27.3, 23.2,
22.9, 21.2, 18.9, 16.8; ESIMS m/z 655.3 [2M + K]+ (5), 639.5 [2M +
Na]+ (60), 347.2 [M + K]+ (33), 331.3 [M + Na]+ (100); HRESIMS
m/z [M + Na]+ 331.1878 (calcd for C18H28NaO4, 331.1880).
mp 65.5-66.8 °C; [R]25 +211.8 (c 0.09, CHCl3); UV (CHCl3) λmax
D
(log ꢀ) 240 (3.12) nm; IR (KBr) νmax 2924, 1755, 1714, 1624, 1259,
1
1025 cm-1; H NMR (CDCl3, 600 MHz) δ 5.71 (1H, s, H-11), 4.56
3â-Mesyloxy-9-epi-sclareolide (24). A solution of 22 (50 mg, 0.19
mmol) in pyridine (2 mL) was cooled to -5f0 °C in an ice/NaCl
bath, and then methanesulfonyl chloride (0.05 mL) was added. The
reaction mixture was stirred at the same temperature for 2 h, and ethyl
acetate was added. The mixture was washed with 5% HCl(aq), water,
saturated aqueous NaHCO3, and brine, dried (MgSO4), filtered, and
concentrated in vacuo. The yellow residue was separated over a silica
gel column (petroleum ether/AcOEt, 4:1) to give compound 24 (62
mg, 96%) as crystals. Compound 24: mp 164.9-165.8 °C; [R]20D -35.1
(c 0.21, AcOEt), [R]20578 -38.9 (c 0.21, AcOEt), [R]20546 -44.3 (c 0.21,
AcOEt), [R]20 -78.2 (c 0.21, AcOEt), [R]20 -127.5 (c 0.21,
(1H, dd, J ) 11.5, 4.5 Hz, H-3), 2.24 (1H, dt, J ) 11.4, 3.2 Hz), 2.08
(3H, s, CH3COO-), 1.89 (1H, dt, J ) 13.1, 3.3 Hz), 1.80-1.86 (3H,
m), 1.71-1.79 (2H, m), 1.64-1.69(2H, m), 1.63, 1.26, 0.96, and 0.92
(each 3H, s, Me); 13C NMR (CDCl3, 150 MHz) δ 186.6, 172.4, 170.8,
113.4, 86.7, 79.8, 44.3, 39.2, 37.8, 36.2, 30.3, 28.4, 27.3, 25.3, 24.1,
21.2, 16.6, 16.2; ESIMS m/z 345.1 [M + K]+ (10), 329.2 [M + Na]+
(100), 307.2 [M + H]+ (20); HRESIMS m/z [M + Na]+ 329.1716 (calcd
for C18H26NaO4, 329.1723).
3â-Hydroxy-9-epi-sclareolide (22). To a stirred solution of com-
pound 2 (100 mg, 0.33 mmol) in methanol (5 mL) was added
magnesium turnings (16 mg, 0.67 mmol). The reaction mixture was
heated and kept refluxing slowly. When Mg was consumed, a second
portion of Mg (16 mg) was added; then the addition was repeated until
the reaction was complete (monitored by TLC). The mixture was cooled
to room temperature, and 5% HCl(aq) was added. The resulting mixture
was extracted with ethyl acetate, and the combined organic layer was
washed with saturated aqueous NaHCO3 and brine, dried over MgSO4,
and concentrated in vacuo. Separation of the residue via silica gel
chromatography (petroleum ether/AcOEt, 4:1) yielded 22 (64 mg, 74%)
as crystals. Compound 22: mp 151.9-154.9 °C; [R]20D -64.3 (c 0.12,
CH3OH), [R]20578 -66.1 (c 0.12, CH3OH), [R]20546 -76.5 (c 0.12, CH3-
OH), [R]20436 -130.4 (c 0.12, CH3OH), [R]20365 -212.2 (c 0.12, CH3-
436
365
AcOEt); IR (KBr) νmax 2935, 1759, 1631, 1349, 1172, 941, 914 cm-1
;
1H NMR (CDCl3, 600 MHz) δ 4.33 (1H, dd, J ) 11.3, 5.2 Hz, H-3),
3.04 (3H, s, CH3SO3-), 2.56 (1H, dd, J ) 17.1, 13.7 Hz, H-11), 2.43
(1H, dd, J ) 17.1, 8.4 Hz, H-11), 1.57 (3H, s, H-16), 1.16, 1.09, and
0.89 (each 3H, s, Me); 13C NMR (CDCl3, 150 MHz) δ 174.8, 88.9,
85.4, 56.3, 46.0, 38.9, 38.2, 36.6, 35.7, 35.5, 32.4, 28.4, 24.8, 22.9,
22.8, 19.1, 16.5; ESIMS m/z 383.1 [M + K]+ (40), 367.2 [M + Na]+
(100); HRESIMS m/z [M + Na]+ 367.1536 (calcd for C17H28NaO5S,
367.1550).
3â-Hydroxy-9-epi-ambrox (26). (1) Starting from 24: LiAlH4 (33
mg, 0.88 mmol) was added to a stirred solution of compound 24 (77
mg, 0.22 mmol) in THF (5 mL) under argon. The mixture was refluxed
slowly for 2 h and then cooled to room temperature. Then, 5% HCl-
(aq) was added, and the mixture was extracted with Et2O three times.
The combined Et2O layer was washed with saturated aqueous NaHCO3
and saturated aqueous Na2SO4, dried over Na2SO4, filtered, and
concentrated in vacuo. Nitromethane (10 mL) and then TsOH‚H2O (19
mg, 0.10 mmol) were directly added to the residue. This mixture was
stirred at room temperature for 6 h, diluted with Et2O, washed with
saturated aqueous NaHCO3 and brine, dried over MgSO4, and filtered.
OH); IR (KBr) νmax 3462, 2928, 1758, 1739, 1388, 1062, 946 cm-1
;
1H NMR (CDCl3, 600 MHz) δ 3.24 (1H, dd, J ) 10.6, 5.6 Hz, H-3),
2.58 (1H, dd, J ) 17.2, 13.6 Hz, H-11), 2.42 (1H, dd, J ) 17.2, 8.3
Hz, H-11), 2.06 (1H, dd, J ) 13.6, 8.3 Hz, H-9), 2.03 (1H, m, H-7),
1.62-1.68 (3H, m, 1H-6 and 2H-2), 1.57 (3H, s, H-16), 1.55 (1H, m,
H-7), 1.32-1.39 (2H, m, H-1 and H-6), 1.26 (1H, m, H-1), 1.12 (3H,
s, H-15), 1.11 (1H, m, H-5),1.05 (3H, s, H-13), 0.81 (3H, s, H-14);
13C NMR (CDCl3, 150 MHz) δ 175.3 (C-12), 85.8 (C-8), 78.6 (C-3),
56.5 (C-9), 45.6 (C-5), 38.5 (C-4), 36.8 (C-7), 36.1 (C-1), 35.8 (C-

Chiral Decalins
Journal of Natural Products, 2006, Vol. 69, No. 11 1537
The filtrate was concentrated in vacuo and purified over a silica gel
column (petroleum ether/AcOEt, 4:1) to afford compound 26 (41 mg,
73%).
3), 38.7 (C-1), 36.0 (C-10), 35.8 (C-7), 33.6 (C-13 or C-14), 32.9 (C-
4), 28.8 (C-11), 27.7 (C-16), 22.8 (C-15), 21.8 (C-13 or C-14), 20.4
(C-6), 18.5 (C-2); EIMS m/z 236 [M]+ (13), 221 [M - Me]+ (100),
206 (19), 151 (6),137 (72), 121 (15), 109 (24), 97 (31), 81 (28), 67
(30), 55 (59), 41 (69).
(2) Starting from 23 with the same procedure as (1), yield: 77%.
Compound 26: colorless needle crystals; mp 132.5-134.6 °C; [R]25
D
-8.0 (c 0.97, CHCl3); [R]25 -8.1 (c 0.97, CHCl3); [R]25 -9.0 (c
578
546
Acknowledgment. The authors are grateful to the National Natural
Science Foundation of China (Grant 20572107), Chengdu Municipal
Bureau of Science & Technology, and the Diao Group for financial
support.
0.97, CHCl3); [R]25 -14.6 (c 0.97, CHCl3); [R]25 -21.1 (c 0.97,
436
365
CHCl3); IR (KBr) νmax 3451, 2965, 2929, 1462, 1384, 1123, 1063, 1037
1
cm-1; H NMR (CDCl3, 600 MHz) δ 3.85 (1H, dt, J ) 9.1, 2.9 Hz),
3.77 (1H, q, J ) 8.5 Hz), 3.22 (1H, dd, J ) 9.0, 7.3 Hz), 1.96-2.05
(1H, m), 1.88-1.94 (1H, m), 1.64-1.68 (3H, m), 1.56-1.62 (3H, m),
1.52 (1H, dt, J ) 13.2, 4.2 Hz), 1.38 (3H, s, Me), 1.17 (1H, dd, J )
12.1, 2.0 Hz), 1.10, 1.02, and 0.79 (each 3H, s, Me); 13C NMR (CDCl3,
150 MHz) δ 80.6, 79.1, 64.0, 58.7, 45.8, 38.6, 36.5, 35.8, 35.4, 28.8,
28.4, 27.6, 27.2, 22.9, 20.1, 15.6; EIMS m/z 252 [M]+ (3), 237 [M -
Me]+ (45), 219 [M - Me - H2O]+ (19), 152 (29), 135 (80), 97 (42),
84 (35), 55 (42), 43 (100).
Supporting Information Available: Experimental data of com-
pounds 13, 15, 17-21, 25, and 29, NMR and selected HRMS spectra
of compounds 2-5, 7, 11, and 13-29, and ORTEP diagrams of 2, 3,
14, 17, 19, 21, 23, and 26. This material is available free of charge via
the Internet at http://pubs.acs.org.
References and Notes
3â-Mesyloxy-9-epi-ambrox (27). A mixture of 26 (50 mg, 0.20
mmol), pyridine (0.2 mL), and CH2Cl2 (3 mL) was cooled to -5 f 0
°C in an ice/NaCl bath, and then methanesulfonyl chloride (0.05 mL)
was added. The mixture was kept at -5f0 °C for 2 h, and additional
CH2Cl2 was added. The mixture was washed with 5% HCl(aq), water,
saturated aqueous NaHCO3, and brine, dried (MgSO4), filtered, and
concentrated in vacuo. The yellow residue was separated over a silica
gel column to give 27 (61 mg, 93%). Compound 27 (pale yellow cubic
crystals): mp 114.8-116.6 °C; [R]25D -4.8 (c 0.08, CHCl3); IR (KBr)
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ν
max 2925, 2858, 1465, 1354, 1334, 1174, 939, 912, 873 cm-1; 1H NMR
(CDCl3, 600 MHz) δ 4.34 (1H, dd, J ) 9.2, 8.0 Hz, H-3), 3.86 (1H,
dt, J ) 8.4, 3.2 Hz, H-12), 3.78 (1H, q, J ) 8.4 Hz, H-12), 3.03 (3H,
s, CH3SO3-), 1.89-2.01 (4H, m), 1.38, 1.14, 1.06 and 0.87 (each 3H,
s, Me); 13C NMR (CDCl3, 150 MHz) δ 90.0, 80.4, 64.0, 58.5, 46.1,
38.9, 38.3, 36.1, 35.5, 35.2, 28.7, 28.5, 27.6, 25.2, 22.7, 20.2, 16.4;
EIMS m/z 330 [M]+ (1), 315 [M - Me]+ (58), 234 [M - CH3SO3H]+
(15), 219 (43), 201 (5), 191 (16), 175 (10), 135 (100).
∆
2(3)-9-epi-Ambrox (28). To a solution of compound 27 (30 mg,
0.09 mmol) in DMF (5 mL) was added anhydrous LiCl (20 mg, 0.47
mmol). The mixture was stirred at 100 °C for 4 h and then cooled to
room temperature. Ethyl acetate was added, and the resulting solution
was washed with water three times and brine, dried over MgSO4, and
filtered. Evaporation in vacuo and purification over a silica gel column
(n-hexane/AcOEt, 50:1) gave 28 (17 mg, 80%) as a colorless oil.
Compound 28: [R]20 -4.3 (c 0.24, CHCl3), [R]20 -5.1 (c 0.24,
D
578
CHCl3), [R]20546 -6.4 (c 0.24, CHCl3), [R]20436 -10.2 (c 0.24, CHCl3),
[R]20365 -13.6 (c 0.24, CHCl3); IR (KBr) νmax 2928, 2866, 1630, 1380,
1132, 1115, 1093, 1055, 1039, 723 cm-1; 1H NMR (CDCl3, 600 MHz)
δ 5.46 (1H, ddd, J ) 9.9, 6.0, 1.6 Hz, H-2), 5.35 (1H, dd, J ) 9.9, 2.7
Hz, H-3), 3.86 (1H, dt, J ) 8.4, 2.7 Hz, H-12), 3.78 (1H, q, J ) 8.4
Hz, H-12), 2.00-2.07 (2H, m, H-1 and H-11), 1.93 (1H, m, H-11),
1.69 (1H, dd, J ) 12.2, 8.2 Hz, H-9), 1.63 (1H, dd, J ) 16.4, 6.0 Hz,
H-1), 1.54-1.60 (3H, m, 1H-6 and 2H-7), 1.50 (1H, dd, J ) 12.5, 2.6
Hz, H-5), 1.39 (3H, s, H-16), 1.35 (1H, m, H-6), 1.11 (3H, s, H-15),
0.98 and 0.88 (each 3H, s, H-13 and H-14); 13C NMR (CDCl3, 150
MHz) δ 137.8 (C-3), 121.6 (C-2), 80.6 (C-8), 63.9 (C-12), 56.9 (C-9),
43.7 (C-5), 38.2 (C-1), 35.1 (C-10), 34.6 (C-7), 34.5 (C-4), 31.7 (C-13
or 14), 29.4 (C-11), 26.9 (C-16), 23.1 (C-15), 22.9 (C-13 or 14), 21.3
(C-6); ESIMS m/z 257.1 [M + Na]+ (90), 235.2 [M + H]+ (100);
HRESIMS m/z [M + H]+ 235.2059 (calcd for C16H27O, 235.2056).
(-)-9-epi-Ambrox (7). To a stainless steel autoclave of 20 mL with
a magnetic stirrer were added a solution of 28 (50 mg) in ethyl acetate
(5 mL) and 10% Pd/C (10 mg). The autoclave was evacuated and
purged with hydrogen three times, and then the pressure of hydrogen
was kept at 4 MPa during the entire reaction process. After 12 h, the
stirring was stopped and the autoclave was vented slowly. Removal of
the Pd/C by filtration and concentration in vacuo gave 7 quantitatively
as a colorless oil. The spectroscopic data were the same as those
published.2a,36 Compound 7: [R]25 -6.2 (c 1.0, CHCl3) (lit.19a [R]25
D
D
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-6.0, c 1.0, CHCl3); IR (KBr) νmax 2924, 2854, 1463, 1260, 1098,
1060, 1048, 1025, 802 cm-1; 1H NMR (CDCl3, 600 MHz) δ 3.85 (1H,
dt, J ) 8.5, 3.0 Hz, H-12), 3.77 (1H, q, J ) 8.5 Hz, H-12), 2.04 (1H,
m, H-11), 1.91 (1H, m, H-11), 1.64 (1H, m, H-2), 1.51-1.59 (4H, m,
H-6, 2H-7, and H-9), 1.39-1.42 (2H, m, H-2 and H-3), 1.37 (3H, s,
H-16), 1.21-1.28 (3H, m, 2H-1 and H-6), 1.19 (1H, dd, J ) 12.4, 1.4
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150 MHz) δ 80.8 (C-8), 64.1 (C-12), 59.0 (C-9), 46.7 (C-5), 42.3 (C-

1538 Journal of Natural Products, 2006, Vol. 69, No. 11
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NP060159A