Preparation of two diastereoisomeric decalin synthons and (-)-ambrox

Article abstract of DOI:10.1002/hlca.200890074

Two diastereoisomeric decalins, (2S,4aS,5S,6R)- and (2S,4aS,5R,6R)-5-(2- hydroxyethyl)-1,1,4a,6-tetramethyldecalin-2,6-diol (5 and 6) were prepared from the degradation products of oleanolic acid. Starting from 6, (-)-ambrox (4) was synthesized.

Full text of DOI:10.1002/hlca.200890074

734
Helvetica Chimica Acta – Vol. 91 (2008)
Preparation of Two Diastereoisomeric Decalin Synthons and
(ꢀ)-Ambrox
by Yi-Peng Xiea)b)c), Bo-Gang Lia), Ying-Gang Luoa), Xiao-Zhen Chena), and Guo-Lin Zhang*a)
a) Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. China
(phone: þ 86-28-85225401; fax: þ 86-28-85225401; e-mail: zhanggl@cib.ac.cn)
b) Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. China
c) Graduate School of the Chinese Academy of Sciences, Beijing 100039, P. R. China
Two diastereoisomeric decalins, (2S,4aS,5S,6R)- and (2S,4aS,5R,6R)-5-(2-hydroxyethyl)-1,1,4a,6-
tetramethyldecalin-2,6-diol (5 and 6) were prepared from the degradation products of oleanolic acid.
Starting from 6, (ꢀ)-ambrox (4) was synthesized.
Introduction. – trans-4,4,8,10-Tetramethyldecalin is a common structural unit in
natural products, especially in the large family of terpenoids. The dominating
construction methods of decalins are Diels – Alder reactions, Robinson annulation,
and cation- or radical-induced polyene cyclization [1]. However, in the synthesis of the
corresponding natural products, these methods are often limited with respect to
suitable starting substrates, selectivity control, and product resolution. Asymmetric
syntheses of natural products containing the 4,4,8,10-tetramethyldecalin unit are
commonly based on chiral synthons from natural terpenes (e.g., sclareol, manool,
abietic acid, communic acid, larixol, carvone, or thujone), as well as from well-
established synthetic chiral materials such as the Wieland – Miescher ketone.
We have obtained the intermediates 1 (seven steps, 42% total yield) and 2 from
oleanolic acid [2]. Natural products possessing a decalin skeleton with a 9b-side chain
are more prevalent, but those with a 9a-side chain play also a very important role.
Polygodial with a 9b-side chain, for example, is an active antifeedant, but polygodial
with a 9a-side chain is inactive [3]. However, (ꢀ)-9-epi-ambrox (3) has a lower
threshold concentration than (ꢀ)-ambrox (4) [4]. Thus, the preparation of intermedi-
ates such as 5 and 6 from the same starting material by only adjusting some procedures
is fascinating, since they could be adapted conveniently for the synthesis of related
natural products and their 9-epimers.
(ꢀ)-Ambrox is a very important and a rather expensive ambergris odorant.
Therefore, many natural materials have been utilized for its preparation, but the
commercial synthesis of (ꢀ)-ambrox uses exclusively sclareol [5]. Sclareol is obtained
predominantly from the plant Salvia sclarea; the available amount and the price can
fluctuate enormously depending on the harvest of Salvia sclarea. Oleanolic acid is
distributed throughout the plant kingdom, and also commercially available for
approximately a third of the price of that of sclareol. Therefore, it is of interest to
use oleanolic acid in natural product synthesis and transformation.
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 91 (2008)
735
Results and Discussion. – For the catalytic hydrogenation of 1, the product with a
9b-side chain was expected, considering the conformation observed in the single-crystal
X-ray structure of 1 [2]. But to our surprise, only product 7 with a 9a-side chain was
obtained in the presence of H2 and 10% Pd/C (Scheme 1). The reduction of compound
1 by Mg/MeOH afforded compound 2 with the same configuration as observed for 7.
Thus, the conformational stability of the five-membered lactone may determine the
stereocontrol.
Scheme 1
We assumed that the lactone-ring-opened product may be suitable as a starting
material to obtain the 9-epimer 6 instead of 5. The stereochemical course of the

736
Helvetica Chimica Acta – Vol. 91 (2008)
hydrogenation may be influenced by a neighboring heteroatom [6][7]. In compound 1,
there is a potential a-OH group adjacent to the C¼C bond. Its affinity to the Pd/C
catalyst surface may result in the addition of H2 syn to the a-OH group [7].
At first, as starting material, the 3-OH tert-butyl(dimethyl)silyl (TBDMS)-
protected compound 8 was used. The lactone ring could not be opened by base
hydrolysis or ester exchange. Referring to the reductive lactone ring opening by LiAlH4
[8][9], even at low temperature (08), the double bond was reduced as well; acetal 9 and
compound 10 with a saturated 9a-side chain were isolated (Scheme 2). The reduction
of the unsaturated lactone with LiAlH4 is a 1,4-reduction process [10]. When DIBAL-
H is used [11][12], and followed by reduction with LiAlH4 or NaBH4, most starting
material 8 was recovered at low temperature (ꢀ 70 to 08.) At elevated temperature
(40 – 608), the reduction of 8 led to a complex product mixture. Using NaBH4 and with
LiCl as additive in 1,2-dimethoxyethane, the desired product 11 containing a C¼C
Scheme 2

Helvetica Chimica Acta – Vol. 91 (2008)
737
bond was obtained, but the yield was low (40%). After examining various reduction
reagents, it was found that the reduction of 8 and 1, respectively, by Red-Al (sodium
bis(2-methoxyethoxy)aluminumhydride) gave triols 11 and 12 in 70 and 75% yield,
respectively (Scheme 2).
With compound 12 in hand, we tested and verified our speculation by catalytic
hydrogenation. Hydrogenation of 12 with 10% Pd/C in 95% EtOH in the presence of
NaNO2 [13][14] gave the saturated triol 6 with a 9b-side chain in 86% yield. Without
NaNO2, a considerable amount of by-products, resulting from hydrogenolysis and
isomerization of the allylic alcohol, were formed.
Based on the results obtained from the reduction of compound 8, the unsaturated
lactone 1 was reduced directly to the saturated triol 5 with 9a-side chain with LiAlH4
under reflux in THF (Scheme 1).
(ꢀ)-Ambrox (4) was synthesized following the procedure for (ꢀ)-9-epi-ambrox (3)
[2] (Scheme 3) with modifications. Intermediate 13 was prepared directly by mesylation
of triol 6 with methanesulfonyl chloride. The primary OH group at C(12) was probably
first mesylated, followed by intramolecular nucleophilic attack by the 8-OH group to
complete the cyclization, and then mesylation of the OH group at C(3) gave compound
13.
Scheme 3
Ring-A-substituted derivatives of (ꢀ)-ambrox, such as 15 – 19 are usually obtained
by the biotransformation of (ꢀ)-ambrox [15]. The yields for these derivatives of (ꢀ)-
ambrox are usually very low, and the fermentation time is long. The inhibitory activity
of these compounds against thymidine phosphorylase in vitro has been evaluated [15d],
but none of them has exhibited substantial potency.
Conclusions. – In summary, (2S,4aS,5S,6R)- and (2S,4aS,5R,6R)-5-(2-hydroxyeth-
yl)-1,1,4a,6-tetramethyldecalin-2,6-diol (5 and 6, resp.) were prepared from the same
starting material 1 by using different reduction sequences of the C¼C bond and the
lactone ring. (ꢀ)-Ambrox (4) was synthesized from 6. These intermediates could be
used for the synthesis of compounds with a 4,4,8,10-tetramethyldecalin skeleton
possessing 9a- or 9b-side chains.

738
Helvetica Chimica Acta – Vol. 91 (2008)
The authors are grateful to the National Natural Science Foundation of China (Grant 20572107) and
Chengdu Municipal Bureau of Science & Technology for financial support.
Experimental Part
General. All solvents including petroleum ether (PE; 60 – 908) were distilled prior to use. Anh. THF
was distilled from Na and benzophenone. Commercial reagents were used without purification. M.p.: X-6
melting point apparatus; uncorrected. Optical rotations: Perkin-Elmer 341 automatic polarimeter. IR
Spectra: Perkin-Elmer FT-IR spectrophotometer. NMR Spectra: Bruker Avance-600 spectrometer with
TMS as internal standard. Electrospray ionization mass spectra (ESI-MS) on a Finnigan LCQDECA mass
spectrometer, and electron ionization mass spectra (EI-MS) on a VG Micromass VG7070E mass
spectrometer.
(2S,4aS,5S,6R)-5-(2-Hydroxyethyl)-1,1,4a,6-tetramethyldecahydronaphthalene-2,6-diol (5). LiAlH4
(49 mg, 1.3 mmol) was added to a soln. of compound 1 (100 mg, 0.32 mmol) in 5 ml THF at r.t. under
Ar. The mixture was refluxed for 4 h, allowed to cool to r.t. The reaction was quenched with H2O ( 50ml),
15% NaOH (50 ml), and additional H2O (150 ml). The resulting suspension was filtered and washed with
THF. The combined filtrate was concentrated under reduced pressure and purified by silica gel (SiO2)
chromatography (PE/acetone 2:1) to afford 5 (79 mg, 92%). Colorless crystals (MeOH). M.p. 164 – 1658.
[a]2D0 ¼ ꢀ2.9 (c ¼ 1.0, MeOH). IR (KBr): 3406, 3370, 2961, 2913, 2857, 1343, 1114, 1033, 932. 1H-NMR
(600 MHz, CD3OD): 3.46 (t, J ¼ 7.6, 2 H); 3.15 (dd, J ¼ 11.4, 4.2, 1 H); 2.03 – 1.99 (m, 1 H); 1.82 – 1.70 (m,
2 H); 1.62 – 1.48 (m, 4 H); 1.44 (s, 3 H); 1.41 – 1.36 (m, 1 H); 1.15 – 1.12 (m, 1 H); 1.12 (s, 3 H); 1.06 (dd,
J ¼ 12.09, 2.49, 1 H); 0.97 (s, 3 H); 0.75 (s, 3 H). 13C-NMR (150 MHz, CD3OD): 78.2; 72.1; 63.7; 56.7;
45.7; 38.2; 37.9; 36.5; 34.4; 30.5; 29.5; 27.0; 26.5; 23.9; 19.9; 14.1. HR-ESI-MS (pos.): 293.2082 ([ M þ
Na]þ, C16H30NaOþ3 ; calc. 293.2087).
D9(11)-3b-[(tert-Butyl)dimethylsilyloxy]sclareolide (¼(3aR,7S,9aS)-7-({[(tert-Butyl)dimethylsilyl]-
oxy}methyl)-3a,6,6,9a-tetramethyl-4,5,5a,6,7,8,9,9a-octahydronaphtho[2,1-b]furan-2(3aH)-one; 8). To a
soln. of 1 (100 mg, 0.33 mmol) in 10 ml MeOH was added NaOH (40 mg, 1 mmol). The mixture was
stirred at r.t. for 4 h. Most of the solvent was removed under reduced pressure, and 30 ml AcOEt was
added. The resulting mixture was washed with H2O and brine, and dried (Na2SO4). After concentration
under reduced pressure, the crude product was obtained and used directly without purification. DMF
(5 ml) was added to the above product and then tert-butyl(chloro)dimethylsilane (TBDMSCl) (230 mg)
and imidazole (113 mg). This mixture was stirred at 908 for 5 h and then cooled to r.t., diluted with 30 ml
AcOEt, washed with brine, and dried (Na2SO4). Concentration of the filtrate under reduced pressure
followed by chromatography (SiO2; PE/AcOEt 10 :1) afforded 8 (110 mg, 90%). Off-white solid. IR
1
(KBr): 2949, 2934, 2860, 1747, 1625, 1463, 1253, 1218, 1191, 1115, 1094, 1076, 955, 881, 837, 775. H-NMR
(600 MHz, CDCl3): 5.51 (s, 1 H); 3.21 (dd, J ¼ 11.0, 4.7, 1 H); 2.30 – 2.28 (m, 1 H); 1.85 – 1.82 (m, 1 H);
1.78 – 1.71 (m, 2 H); 1.70 – 1.66 (m, 1 H); 1.64 – 1.62 (m, 1 H); 1.55 (s, 3 H); 1.20 (s, 3 H); 0.93 (s, 3 H); 0.90
(br., 9 H); 0.85 (s, 3 H); 0.06 (s, 3 H); 0.04 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 184.2; 172.2; 109.6;
87.1; 78.6; 54.7; 40.6; 40.3; 39.4; 35.2; 28.6; 27.3; 25.8 (3 C); 25.3; 19.5; 18.2; 18.1; 15.9; ꢀ 3.8; ꢀ 5.0. HR-
ESI-MS (pos.): 401.2487 ([ M þ Na]þ, C22H38NaO3Siþ; calc. 401.2482).
(3aR,7S,9aS,9bS)-7-({[(tert-Butyl)dimethylsilyl]oxy}methyl)-3a,6,6,9a-tetramethyldodecahydro-
naphtho[2,1-b]furan-2-ol (9). To a soln. of 8 (100 mg, 0.26 mmol) in anh. THF (10 ml) was added 20 mg
(0.53 mmol) of LiAlH4 at 08 under Ar atmosphere. The soln. was stirred at 08 for 2 h, followed by
addition of H2O (0.1 ml), 15% NaOH (0.1 ml), and additional H2O (0.3 ml). The suspension was filtered,
and the precipitate was washed with THF. The filtrate was combined and concentrated under reduced
pressure. Purification of the residue by chromatography (SiO2; PE/AcOEt 4 :1) afforded compound 9
(49 mg, 48%) as an off-white solid. IR (KBr): 3434, 2951, 2858, 1651, 1465, 1389, 1361, 1253, 1095, 1073,
880, 836, 774. 1H-NMR (600 MHz, CDCl3): 5.48 – 5.45, 5.34 – 5.33 (2m, 1 H); 3.17 (dd, J ¼ 7.0, 4.4, 1 H);
1.97 – 1.94, 1.90 – 1.87 (2m, 2 H); 1.46, 1.45 (2s, 3 H); 1.11, 1.09 (2s, 3 H); 0.94, 0.93 (2s, 3 H); 0.89 (br.,
9 H); 0.75, 0.74 (2s, 3 H); 0.05, 0.04, 0.03, 0.02 (4s, 6 H). 13C-NMR (150 MHz, CDCl3): 97.2; 95.9; 83.3;
82.4; 79.6; 59.4; 55.2; 46.2; 45.5; 39.1; 38.2; 37.7; 37.6; 36.6; 36.5; 36.3; 35.8; 35.3; 29.3; 28.9; 28.8; 27.8; 27.6;
27.6; 25.9; 22.9; 22.9; 20.5; 20.1; 18.1; 16.2; 16.0; ꢀ 3.8; ꢀ 4.9. HR-ESI-MS (pos.): 405.2791 ([ M þ Na]þ,
C22H42NaO3Siþ; calc. 405.2795).

Helvetica Chimica Acta – Vol. 91 (2008)
739
(1Z,2R,6S,8aS)-6-({[(tert-Butyl)dimethylsilyl]oxy}methyl)-1-(2-hydroxyethylidene)-2,5,5,8a-tetra-
methyldecahydronaphthalen-2-ol (11). To a stirred soln. of 8 (40 mg, 0.11 mmol) in anh. THF (10 ml) was
syringed 90 ml of Red-Al (70 wt.-% in toluene, 0.32 mmol) at r.t. under Ar. The mixture was stirred at 608
for 7 h, followed by quenching the reaction with 2 ml of 23% aq. potassium sodium tartrate (Rochelle
salt), and the mixture was stirred vigorously until the soln. turned clear. AcOEt (10 ml) was added to the
mixture, the org. layer was separated, and the aq. layer was extracted with AcOEt. The combined org.
layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduce pressure. The
residue was purified by chromatography (SiO2; PE/AcOEt 2 :1) to afford 11 (28 mg, 70%) as off-white
solid. IR (KBr): 3411, 2930, 2857, 1473, 1463, 1386, 1368, 1251, 1110, 1074, 1008, 943, 886, 837, 771.
1H-NMR (600 MHz, CDCl3): 5.52 (t, J ¼ 6.3, 1 H); 4.44 (dd, J ¼ 13.2, 6.5, 1 H); 4.30 (dd, J ¼ 13.2, 6.1,
1 H); 3.17 (dd, J ¼ 11.2, 4.9, 1 H); 1.98 (dt, J ¼ 12.4, 3.3, 1 H); 1.81 (dt, J ¼ 13.0, 3.4, 1 H); 1.72 – 1.66 (m,
2 H); 1.65 – 1.61 (m, 2 H); 1.57 – 1.52 (m, 3 H); 1.41 – 1.37 (m, 1 H); 1.26 (s, 3 H); 1.09 (s, 3 H); 1.01 (dd,
J ¼ 11.7, 2.5, 1 H); 0.92 (s, 3 H); 0.89 (br., 9 H); 0.77 (s, 3 H); 0.05 (s, 3 H); 0.03 (s, 3 H). 13C-NMR
(150 MHz, CDCl3): 157.7; 122.0; 78.8; 74.4; 60.2; 52.0; 45.4; 40.4; 39.8; 37.3; 30.6; 28.6; 28.2; 25.9 (3 C);
23.7; 19.8; 18.1; 15.9; ꢀ 3.8; ꢀ 5.0. HR-ESI-MS (pos.): 405.2805 ([ M þ Na]þ, C22H42NaO3Siþ; calc.
405.2795).
(2S,4aS,5Z,6R)-5-(2-Hydroxyethylidene)-1,1,4a,6-tetramethyldecahydronaphthalene-2,6-diol (12).
The process was similar to the preparation of 11. Yield: 75%. Colorless crystal (MeOH). M.p. 201 –
202.58. [a]2D0 ¼ þ5.3 (c ¼ 1.0, MeOH). IR (KBr): 3351, 2971, 2933, 2861, 1622, 1471, 1073, 1043, 975,
930. 1H-NMR (600 MHz, CD3OD): 5.37 (dd, J ¼ 5.9, 4.1, 1 H); 4.49 (dd, J ¼ 14.8, 6.1, 1 H); 4.40 (dd, J ¼
14.8, 3.8, 1 H); 3.14 (dd, J ¼ 9.4, 7.0, 1 H); 1.93 – 1.90 (m, 2 H); 1.73 – 1.68 (m, 3 H); 1.61 – 1.57 (m, 1 H);
1.55 – 1.50 (m, 1 H); 1.48 – 1.43 (m, 1 H); 1.41 (s, 3 H); 1.12 (s, 3 H); 1.03 (dd, J ¼ 11.4, 2.2, 1 H); 0.99 (s,
3 H); 0.80 (s, 3 H). 13C-NMR (150 MHz, CD3OD): 154.7; 124.0; 77.8; 73.0; 60.1; 52.1; 44.4; 40.0; 38.9;
37.4; 28.4; 27.4; 27.1; 23.1; 19.3; 14.7. HR-ESI-MS (pos.): 291.1926 ([ M þ Na]þ, C16H28NaO3þ ; calc.
291.1931).
(2S,4aS,5R,6R)-5-(2-Hydroxyethyl)-1,1,4a,6-tetramethyldecahydronaphthalene-2,6-diol (6). a) Start-
ing from 12. To a soln. of 12 (80 mg, 0.3 mmol) in 95% EtOH (10 ml) was added 10% Pd/C (10 mg) and
NaNO2 (1 mg). After stirring for 30 min, the mixture was hydrogenated for 16 h at r.t. Pd/C was removed
by filtration, and the filtrate was concentrated. The residue was purified by chromatography (SiO2; PE/
acetone 2:1) to give 6 (69 mg, 86%) as an off-white solid.
b) Starting from 11. Substrate 11 (50 mg, 0.13 mmol) was used. The hydrogenation procedure was
analogous to the hydrogenation of 12. After removal of Pd/C and the solvent, a residue was obtained, to
which MeOH (5 ml) and 1n HCl (0.5 ml) were added. The mixture was stirred at r.t. for 6 h. AcOEt
(30 ml) was added, and the resulting soln. was washed with sat. aq. NaHCO3, brine, and dried (Na2SO4),
filtered, and concentrated under reduced pressure. The residue was purified by chromatography (SiO2;
PE/acetone 2:1) to give 6 (29 mg, 82% two steps). Colorless crystal (MeOH). M.p. 207 – 2088. [a]D20
¼
ꢀ8.4 (c ¼ 1.0, MeOH). IR (KBr): 3406, 3352, 2958, 2931, 2874, 2855, 1629, 1130, 1043, 905. 1H-NMR
(600 MHz, CD3OD): 3.60 – 3.51 (m, 2 H); 3.15 (dd, J ¼ 11.4, 4.9, 1 H); 1.87 – 1.84 (m, 1 H); 1.74 – 1.71 (m,
1 H); 1.70 – 1.66 (m, 2 H); 1.64 – 1.54 (m, 3 H); 1.16 (s, 3 H); 1.09 – 1.04 (m, 2 H); 0.97 (s, 3 H); 0.92 – 0.90
(m, 1 H); 0.84 (s, 3 H); 0.76 (s, 3 H). 13C-NMR (150 MHz, CD3OD): 78.1; 72.4; 63.6; 58.1; 55.1; 43.5; 38.5;
38.3; 37.8; 27.9; 27.3; 26.4; 22.7; 19.8; 14.6 (2 C). HR-ESI-MS: 293.2082 ([M þ Na]þ, C16H30NaO3þ ; calc.
293.2087).
Compound 6 has also been obtained from the biotransformation of (ꢀ)-ambrox (4) [15c][16].
3b-(Mesyloxy)-9-ambrox (¼ [(3aR,7S,9aS,9bR)-3a,6,6,9a-Tetramethyldodecahydronaphtho[2,1-
b]furan-7-yl]methyl Methanesulfonate; 13). MsCl (0.05 ml) was added to a mixture of 6 (50 mg,
0.20 mmol), pyridine (0.2 ml), and CH2Cl2 (3 ml), the mixture was stirred at r.t. for 5 h, and then AcOEt
(15 ml) was added. The resulting soln. was washed with 5% HCl (aq.), sat. aq. NaHCO3, and brine, and
dried (Na2SO4). The filtrate was concentrated under reduced pressure, and the residue was purified by
chromatography (SiO2; PE/AcOEt 4 :1) to give 13 (57 mg, 93%). Colorless crystals (AcOEt). M.p. 150 –
151.58. [a]2D0 ¼ ꢀ15.6 (c ¼ 1.0, CHCl3). IR (KBr): 2971, 2951, 2927, 2878, 1350, 1332, 1170, 1004, 923, 906.
1H-NMR (600 MHz, CDCl3): 4.36 (dd, J ¼ 11.1, 5.8, 1 H); 3.90 – 3.94 (m, 1 H); 3.84 (q, J ¼ 8.0, 1 H); 3.02
(s, 3 H); 2.03 – 1.95 (m, 3 H); 1.80 – 1.71 (m, 3 H); 1.59 – 1.57 (m, 1 H); 1.44 – 1.33 (m, 3 H); 1.26 – 1.21 (m,
1 H); 1.09 (s, 3 H); 1.05 (s, 3 H); 1.02 – 0.99 (m, 1 H); 0.89 (s, 3 H); 0.88 (s, 3 H). 13C-NMR (150 MHz,

740
Helvetica Chimica Acta – Vol. 91 (2008)
CDCl3): 90.0; 79.6; 64.9; 59.8; 56.1; 39.4; 38.8; 38.6; 37.8; 35.7; 28.4; 25.1; 22.6; 21.0; 20.4; 16.0; 15.1. HR-
ESI-MS (pos.): 683.3624 ([2 M þ Na]þ, C34H60NaO8S2þ ; calc. 683.3622).
The procedures for the syntesis of D2(3)-ambrox (14) from 3b-(mesyloxy)-9-ambrox (13), and (ꢀ)-
ambrox (4) are similar to those in [2] (Scheme 3).
D2(3)-Ambrox (¼(3aR,9aS,9bR)-3a,6,6,9a-Tetramethyl-1,2,3a,4,5,5a,6,9,9a,9b-decahydronaph-
tho[2,1-b]furan; 14). Colorless crystals (AcOEt). M.p. 88 – 898. [a]2D0 ¼ þ12.2 (c ¼ 1.0, CHCl3). IR
1
(KBr): 2925, 2866, 1632, 1380, 1132, 1115, 1093, 1055, 1039, 723. H-NMR (600 MHz, CDCl3): 5.45 (ddd,
J ¼ 10.0, 5.3, 2.4, 1 H); 5.40 (dd, J ¼ 10.1, 2.4, 1 H); 3.93 (dt, J ¼ 9.0, 3.0, 1 H); 3.84 (q, J ¼ 8.3, 1 H); 1.99 –
1.97 (m, 1 H); 1.83 – 1.73 (m, 5 H); 1.47 – 1.37 (m, 3 H); 1.30 – 1.26 (m, 1 H); 1.11 (s, 3 H); 0.99 (s, 3 H);
0.91 (s, 3 H); 0.88 (s, 3 H). 13C-NMR (150 MHz, CDCl3): 138.6; 121.2; 79.8; 64.9; 58.9; 52.9; 40.5; 39.1;
35.2; 34.5; 31.9; 22.7; 22.2; 21.5; 20.5; 15.2. ESI-MS: 257.1 ([ M þ Na]þ).
(ꢀ)-Ambrox (¼(3aR,9aS,9bR)-3a,6,6,9a-Tetramethyldodecahydronaphtho[2,1-b]furan; 4). Color-
less crystals (AcOEt). M.p. 73 – 758 ([17a]: 74 – 768, [17b]: 77 – 77.58). [a]2D0 ¼ ꢀ25.0 (c ¼ 1.0, CHCl3)
([17a]: [a]2D0 ¼ ꢀ24.7, c ¼ 1.0, CHCl3; [17b]: [a]D25 ¼ ꢀ25.1, c ¼ 1.0, CHCl3). IR (KBr): 2924, 2854, 1463,
1260, 1098, 1060, 1048, 1025, 802. The 1H- and 13C-NMR, and MS data were identical with those in
[17][18].
REFERENCES
[1] T. Tricotet, R. Brückner, Eur. J. Org. Chem. 2007, 1069.
[2] H.-J. Yang, B.-G. Li, X.-H. Cai, H.-Y. Qi, Y.-G. Luo, G.-L. Zhang, J. Nat. Prod. 2006, 69, 1531.
[3] B. J. M. Jansen, A. de Groot, Nat. Prod. Rep. 1991, 8, 309.
[4] L. A. Paquette, R. E. Maleczka Jr., J. Org. Chem. 1991, 56, 912.
´
[5] G. Frater, J. A. Bajgrowicz, P. Kraft, Tetrahedron 1998, 54, 7633.
[6] M. Bartok, J. Czombos, K. Felfoldi, L. Gera, G. Gondos, A. Molnar, F. Notheisz, I. Palinko, G.
Wittmann, A. G. Zsigmond, in ꢁStereochemistry of Heterogeneous Metal Catalysisꢂ, Wiley,
Chichester, 1985.
[7] A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem. Rev. 1993, 93, 1307.
[8] C. E. Masse, M. Yang, J. Solomon, J. S. Panek, J. Am. Chem. Soc. 1998, 120, 4123.
[9] D. R. Williams, A. L. Nold, R. J. Mullins, J. Org. Chem. 2004, 69, 5374.
[10] M. B. Smith, in ꢁOrganic Synthesisꢂ, 2nd edn., McGraw-Hill, 2001, p. 311.
[11] N. Sydorenko, R. P. Hsung, O. S. Darwish, J. M. Hahn, J. Liu, J. Org. Chem. 2004, 69, 6732.
[12] M. Shindo, T. Sugioka, Y. Umaba, K. Shishido, Tetrahedron Lett. 2004, 45, 8863.
[13] E. G. Nidy, R. A. Johnson, J. Org. Chem. 1975, 40, 1415.
[14] J.-M. Poudrel, P. Hullot, J.-P. Vidal, J.-P. Girard, J.-C. Rossi, A. Muller, C. Bonne, V. Bezuglov, I.
Serkov, P. Renard, B. Pfeiffer, J. Med. Chem. 1999, 42, 5290.
[15] a) J. R. Hanson, A. Truneh, Phytochemistry, 1996, 42, 1021; b) A. Farooq, S. Tahara, Z. Naturforsch.,
C 2000, 55, 341; c) M. I. Choudhary, S. G. Musharraf, A. Sami, Atta-ur-Rahman, Helv. Chim. Acta
2004, 87, 2685; d) A. Nasib, S. G. Musharraf, S. Hussain, S. Khan, S. Anjum, S. Ali, Atta-ur-Rahman,
M. I. Choudhary, J. Nat. Prod. 2006, 69, 957.
[16] T. Hashimoto, Y. Noma, Y. Asakawa, Heterocycles 2001, 54, 529.
[17] a) J. P. Kutney, Y.-H. Chen, Can. J. Chem. 1994, 72, 1570; b) G. Ohloff, W. Giersch, W. Pickenhagen,
A. Furrer, B. Frei, Helv. Chim. Acta 1985, 68, 2022.
[18] S. Nakamura, K. Ishihara, H. Yamamoto, J. Am. Chem. Soc. 2000, 122, 8131.
Received November 14, 2007