Concise syntheses of coronarin A, coronarin E, austrochaparol and pacovatinin A

Article abstract of DOI:10.1248/cpb.56.398

Total syntheses of (+)-coronarin A (1), (+)-coronarin E (2), (+)-austrochaparol (3) and (+)-pacovatinin A (4) were achieved from the synthetic (+)-albicanyl acetate (6). Dess-Martin oxidation of (+)-albicanol (5) derived from the chemoenzymatic product (6) gave an aldehyde (7), which was subjected to Julia one-pot olefination using β-furylmethyl-heteroaromatic sulfones (8 or 9 ) gave (+)-trans coronarin E (2) and (+)-cis coronarin E (12) with high cis-selectivity. The synthesis of (+)-coronarin A (1) from (+)-trans coronarin E (2) was achieved, while (+)-cis coronarin E (12) was converted to the natural products (+)-(5S,9S,10S)-15,16-epoxy-8(17),13(16),14-labdatriene (13) and (+)-austrochaparol (3). By the asymmetric synthesis of (+)-3, the absolute structure of (+)-3 was determined to be 5S, 7R, 9R, 10S configurations. Homologation of (+)-albicanol (5) followed by allylic oxidation gave (7α)-hydroxy nitrile (17), which was finally converted to the natural (+)-pacovatinin A (4) in 8 steps from (+)-albicanol (5).

Full text of DOI:10.1248/cpb.56.398

398
Notes
Chem. Pharm. Bull. 56(3) 398—403 (2008)
Vol. 56, No. 3
Concise Syntheses of Coronarin A, Coronarin E, Austrochaparol and
Pacovatinin A
Takahiro MIYAKE,a,b Keisuke UDA,a Masako KINOSHITA,a Mikio FUJII,a and Hiroyuki AKITA*,a
a Faculty of Pharmaceutical Sciences, Toho University; 2–2–1 Miyama, Funabashi, Chiba 274–8510, Japan: and
b Tsukuba Research Institute, Novartis Pharma Co., Ltd.; 8 Ohkubo, Tsukuba, Ibaraki 300–2611, Japan.
Received November 15, 2007; accepted December 13, 2007; published online December 19, 2007
Total syntheses of (ꢀ)-coronarin A (1), (ꢀ)-coronarin E (2), (ꢀ)-austrochaparol (3) and (ꢀ)-pacovatinin A
(4) were achieved from the synthetic (ꢀ)-albicanyl acetate (6). Dess–Martin oxidation of (ꢀ)-albicanol (5)
derived from the chemoenzymatic product (6) gave an aldehyde (7), which was subjected to Julia one-pot olefina-
tion using b-furylmethyl-heteroaromatic sulfones (8 or 9 ) gave (ꢀ)-trans coronarin E (2) and (ꢀ)-cis coronarin E
(12) with high cis-selectivity. The synthesis of (ꢀ)-coronarin A (1) from (ꢀ)-trans coronarin E (2) was achiev-
ed, while (ꢀ)-cis coronarin E (12) was converted to the natural products (ꢀ)-(5S,9S,10S)-15,16-epoxy-
8(17),13(16),14-labdatriene (13) and (ꢀ)-austrochaparol (3). By the asymmetric synthesis of (ꢀ)-3, the absolute
structure of (ꢀ)-3 was determined to be 5S, 7R, 9R, 10S configurations. Homologation of (ꢀ)-albicanol
(5) followed by allylic oxidation gave (7a)-hydroxy nitrile (17), which was finally converted to the natural (ꢀ)-
pacovatinin A (4) in 8 steps from (ꢀ)-albicanol (5).
Key words (ꢀ)-coronarin A; (ꢀ)-coronarin E; (ꢀ)-austrochaparol; (ꢀ)-pacovatinin A; total synthesis
There are many natural products possessing a labdane The structures of these compounds are established by chemi-
skeleton in nature. Among them, (ꢀ)-coronarin A (1),1) (ꢀ)- cal and spectroscopic methods. The absolute structure of 1
coronarin E (2),2) (ꢀ)-austrochaparol (3)3) and (ꢀ)-pacova- was determined based on the allyic benzoate rule, because
tinin A (4)4) are typical compounds (Chart 1). For the synthe- the p-bromobenzoate of 1 showed a positive cotton curve at
sis of these compounds, (ꢀ)-albicanol (5) is the desirable 245 nm.1) (ꢀ)-Austrochaparol (3) is isolated from the aerial
compound as starting material. We reported that lipase-as- parts of Austroeupatorium chaparense and its absolute struc-
sisted resolution of racemic albicanol (ꢁ)-5 gave (ꢀ)-albi- ture has not been determined yet.3) The synthesis of (ꢀ)-1
canyl acetate (6, 56%, 67% ee) and (ꢂ)-albicanol (5, 38%, was achieved from natural product, (ꢀ)-sclareolide in ten
ꢃ99% ee) in the presence of acylating reagent.5) Hydrolysis steps.6) For the synthesis of these compounds, carbon–carbon
of 67% ee of (ꢀ)-6 gave 67% ee of (ꢀ)-albicanol (5), which bond formation between an aldehyde (7) and b-furylmethyl
was again subjected to lipase-assisted resolution to obtain the unit sulfone A or phosphonium salt B is necessary as shown
optically pure (ꢀ)-6 in 53% yield. This chemoenzymatic in Chart 2.
procedure was found to be effective for procurement as start-
The aldehyde (7) could be derived from the present enzy-
ing material for the synthesis of chiral decaline type matic product (6). Wittig reaction of 7 and phosphonium salt
sesquiterpenoids and diterpenoids. Herein we report the con- B was reported to give 2 in 32% yield.7) To overcome the low
cise synthesis of (ꢀ)-coronarin A (1), (ꢀ)-coronarin E (2), yield of this carbon–carbon bond formation process, one-pot
(ꢀ)-austrochaparol (3) and (ꢀ)-pacovatinin A (4) from (ꢀ)- Julia coupling8) of 7 and heteroaromatic sulfone A (8 or 9)
albicanyl acetate (6).
possessing b-furylmethyl moiety was carried out. The
Synthesis of (ꢀ)-Coronarin A (1), (ꢀ)-Coronarin E (2) straightforward synthesis of these compounds from (ꢀ)-albi-
and (ꢀ)-Austrochaparol (3) The furanolabdane diter- canyl acetate (6) is shown in Chart 3.
penoids, coronarin A (1) and coronarin E (2), are isolated
The synthesis of the desired sulfone A was shown in Chart
from rhizomers of the Brazilian antirheumatic medicinal 3. The reaction of 3-furylmethanol with 2-mercaptobenzo-
plant, Hedychium Coronarium (Zingiberaceae).1,2) These thiazole (BTSH) or 1-phenyl-1H-tetrazol-5-thiol (PTSH) in
compounds exhibit a significant cytotoxic effect against Chi- the presence of triphenylphosphine (Ph3P) and diethylazodi-
nese hamster V-79 cells and sarcoma 180 ascites in mice.1) carboxylate (DEAD) gave sulfides (10, 91% yield) or (11,
91% yield), which was separately oxidized with m-chloroper-
benzoic acid (m-CPBA) to afford sulfones (8, 67% yield) or
(9, 31% yield), respectively. Treatment of (ꢀ)-albicanyl
acetate (6) with K2CO3 gave (ꢀ)-albicanol (5) in quantitative
yield, which was treated with Dess–Martin reagent to afford
Chart 1
Chart 2
∗ To whom correspondence should be addressed. e-mail: akita@phar.toho-u.ac.jp
© 2008 Pharmaceutical Society of Japan

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399
Table 1. Stereoselectivity by One-Pot Julia Coupling
Hetero-sulfone
Yield
(%)
Entry
Base
Solvent
cis-12 : trans-2
(8 or 9)
1
2
3
4
5
8
8
8
8
9
LiN(TMS)2
NaN(TMS)2
KN(TMS)2
KN(TMS)2
KN(TMS)2
THF
THF
THF
DME
DME
88
74
75
86
73
87 : 13
88 : 12
91 : 9
97 : 3
98 : 2
Chart 3
the aldehyde (7) in 83% yield. The Julia one-pot olefination
between an aldehyde (7) and sulfone (8) in the presence of
lithium bis(trimethylsilylamide) gave (ꢀ)-coronarin E (2,
11% yield) and (ꢀ)-cis-coronarin E (12, 77% yield, [a]D23
Chart 4
ꢀ109.1° (cꢄ0.44, CHCl3)). The physical data ([a]D20 ꢀ22.4° isolated from seeds of the Brazilian medicinal plant, Re-
1
(cꢄ1.40, CHCl3) and H-NMR) of the synthetic (ꢀ)-2 were nealmia exaltata L.f. (Zingiberaceae), and its structure in-
1
identical with those ([a]D ꢀ22.3° (cꢄ0.44, CHCl3) and H- cluding absolute configurations was elucidated by spectro-
1
NMR)2) of the natural (ꢀ)-2. The H-NMR data of the syn- scopic analysis and a modified Mosher method.4) On the
thetic (ꢀ)-12 were in agreement with those of the reported other hand, hedychilactone A (4) was isolated from the
(ꢀ)-12 derived from natural (ꢂ)-sclareol.9) When the reac- methanolic extract of the fresh rhizome of Hedychium coro-
tion conditions (sulfone 8 or 9, base, solvent) were changed narium KOENG, and found to inhibit the increase of vascular
for the purpose of improvement of ratio of trans-(ꢀ)-2, the permeability induced by acetic acid in mice and nitric oxide
results were as shown in Table 1 (entries 1—5). High cis-se- production in lipopolysaccharide-activated mouse peritoneal
lectivity was observed in every case.
macrophages.11,12) Interestingly, hedychilactone A has been
Hydrogenation of the main cis-(ꢀ)-12 in the presence of already reported under a different name, pacovatinin A (4).
quinoline and 5% Pd–BaSO4 gave compound (ꢀ)-13 (86% The straightforward synthesis of (ꢀ)-4 from (ꢀ)-5 is shown
yield, [a]D23 ꢀ44.1° (cꢄ0.59, CHCl3)), which was in accord in Chart 4.
with the reported natural product (ꢀ)-(5S,9S,10S)-15,16-
Homologation of (ꢀ)-5 was accomplished by displace-
epoxy-8(17),13(16),14-labdatriene (13, [a]D26 ꢀ49.3° (cꢄ1.00, ment of the hydroxyl group with cyanide under Mitsunobu
CHCl3)).10) Allylic oxidation of (ꢀ)-13 with SeO2 gave (ꢀ)- conditions13,14) in the presence of acetone cyanohydrin to
austrochaparol (3, 50% yield, [a]D27 ꢀ5.6° (cꢄ0.50, CHCl3)). give nitrile 16 in 64% yield. H- and 13C-NMR data of the
1
The physical data ([a]D and 1H-NMR) of the synthetic (ꢀ)-3 synthetic 16 were identical with those of the reported (ꢀ)-16
were identical with those ([a]D24 ꢀ8.5° (cꢄ6.11, CHCl3) and by us.15) Allylic oxidation of 16 using a combination of SeO2
1H-NMR) of natural 3.3) Consequently, absolute configura- and tert-BuOOH gave the 7a-hydroxy compound (17) in
tions of natural 3 were confirmed to be 5S, 7R, 9R, 10S. Gen- 79% yield. Stereochemical inversion of 7a-configuration to
eration of 7a-hydroxy compound (3) could be explained by 7b-configuration was achieved by the Mitsunobu method.16)
an attack of the reagent from the less-hindered a-side. More- Treatment of 17 with benzoic acid in the presence of Ph3P
over, allylic oxidation of (ꢀ)-2 with SeO2 afforded (ꢂ)-epi- and diethylazodicarboxylate (DEAD) afforded 7b-acyloxy
coronarin A (14, 47% yield, [a]D23 ꢂ13.4° (cꢄ1.16, CHCl3)), nitrile (18, 79% yield), which was treated with K2CO3 in
which was subjected to oxidation with Dess–Martin reagent MeOH to provide 6b-alcohol (19) in 78% yield. Silylation of
to give a a,b-unsaturated ketone (15). NaBH4 reduction of the secondary alcohol group of 19 followed by Dibal reduc-
15 gave (ꢀ)-coronarin A [(1, mp 99—101 °C, [a]D23 ꢀ26.9° tion gave an aldehyde (21) in overall 84% yield (2 steps from
(cꢄ0.35, CHCl3)] in 78% yield from (ꢀ)-14. The physical 19). Horner–Emmons condensation of 21 and diethoxyphos-
data of the synthetic (ꢀ)-1 were identical with those (mp phonobutyrolactone in the presence of tert-BuOK gave the
100—101 °C, [a]D ꢀ25.4° (cꢄ0.28, CHCl3) and 1H-NMR)1) less polar compound (22, 27% yield) and the more polar one
of the natural (ꢀ)-1.
(23, 63% yield). Deprotection of silyl group of 23 provided
Synthesis of Pacovatinin A (4) Pacovatinin A (4) was (ꢀ)-4 [[a]D24 ꢀ12.8° (cꢄ1.0, CHCl3), 92% yield], of which

400
Vol. 56, No. 3
Chart 5. Proposed Mechanism for the One-Pot Julia Olefination
spectral data (1H- and 13C-NMR) were identical with those of were confirmed to be 5S, 7R, 9R, 10S. Homologation of albi-
the reported (ꢀ)-4 [[a]D23 ꢀ10.0° (cꢄ1.00, CHCl3)].4)
canol (ꢀ)-5 followed by allylic oxidation gave (7a)-hydroxy
nitrile 17, which was subjected to the Mitsunobu reaction to
provide the desired (7b)-acyloxy nitrile 18. This compound
Discussion
Julia one-pot olefination between aldehyde (7) and BT-sul- was converted to the (7b)-siloxy aldehyde 21, which was
fone (8) gave (ꢀ)-cis-coronain E (12) with high cis-selectiv- subjected to the Horner–Emmons reaction to afford the de-
ity. This high selectivity could be explained as shown in sired trans g-lactone 23. Deprotection of the silyl group of
Chart 5.
23 gave the natural (ꢀ)-pacovatinin A (4) in 15% overall
Metallated BT-sulfone (8) condenses with aldehyde (7) to yield (8 steps) from (ꢀ)-albicanol (5).
give anti isomer (24) and syn isomer (25), which are con-
verted to intermediates 26 and 27, respectively. Direct loss of
lithio-benzothiazolone and sulfur dioxide from intermediates
26 and 27 may yield trans isomer (2) via 28 and cis isomer
(12) via 29, respectively. The energy barrier to Smiles
rearrangement for the anti isomer (24) is presumably higher
than that for the corresponding syn isomer (25) due to the
eclipsed/gauche arrangement of R5 and R6 in the appropriate
transition state for spirocyclisation. Therefore, the formation
rate of 26 from 24 may be slow, while that of 27 from 25 may
be fast. The possibility of addition/retroaddition in the reac-
tion of metallated BT-sulfone with aldehyde has been estab-
lished experimentally.7) Equilibration between 24 and 25 to-
gether with faster Smiles rearrangement/elimination for the
latter provide a reasonable explanation for the high cis-selec-
tivity.
Experimental
All melting points were measured on a Yanaco MP-3S micro melting
point apparatus and are uncorrected. 1H-NMR spectra were recorded on a
JEOL EX 400 spectrometer. Spectra were taken with 5—10% (w/v) solution
in CDCl3 with Me4Si as an internal reference. The mass spectra, FAB and
EI, were obtained with a JEOL JMS-600 H (matrix; glycerol, m-nitrobenzyl
alcohol) or a JEOL JMS-AM II 50 spectrometer, respectively. IR spectra
were recorded on a JASCO FT/IR-300 spectrometer. Optical rotations were
measured with a JASCO DIP-370 digital polarimeter. All evaporations were
performed under reduced pressure. For column chromatography, silica gel
(Kieselgel 60) was employed.
3-Furylmethyl Benzothiazol-2-yl Sulfide (10) To a solution of 3-furyl-
methanol (3.01 g, 30.6 mmol) in THF (70 ml) was added 2-mercaptoben-
zothiazole (10.2 g, 61.2 mmol), Ph3P (16.0 g, 61.2 mmol) and 2.2 M diethyl-
azodicarboxylate (DEAD) in toluene solution (28 ml, 61.2 mmol) at 0 °C and
the whole mixture was stirred under argon atmosphere for 14 h at room tem-
perature (rt). The reaction mixture was diluted with 2 M aqueous NaOH and
extracted with Et2O. The organic layer was washed with brine, and dried
over MgSO4. The organic layer was evaporated to give a crude residue,
which was chromatographed on silica gel (150 g, n-hexane : AcOEtꢄ100 : 1)
to afford 10 (6.90 g, 91%) as a pale yellow oil. 10: IR (neat): 3126, 3062,
Conclusion
Total syntheses of (ꢀ)-coronarin A (1), (ꢀ)-coronarin E 1503 cmꢂ1 1H-NMR d: 4.42 (2H, br s), 6.44 (1H, br s), 7.28 (1H, ddd,
;
Jꢄ9.0, 7.2, 1.2 Hz), 7.35 (1H, br s), 7.41 (1H, ddd, Jꢄ8.0, 7.2, 1.2 Hz), 7.47
(1H, m), 7.74 (1H, ddd, Jꢄ9.0, 1.2, 0.8 Hz), 7.88 (1H, ddd, Jꢄ9.0, 1.2,
0.8 Hz). 13C-NMR d: 28.0, 111.0, 120.3, 121.0, 121.5, 124.3, 126.1, 135.3,
141.1, 143.3, 153.0, 166.2. Anal. Calcd for C12H9NOS2: C, 58.27; H, 3.67;
N, 5.66. Found: C, 58.36; H, 3.86; N, 5.31. HR-MS (EI) Calcd for
C12H9NOS2: 247.0126. Found: 247.0127.
(2), (ꢀ)-austrochaparol (3) and (ꢀ)-pacovatinin A (4) were
achieved from (ꢀ)-albicanyl acetatel (6), which was effec-
tively obtained based on the enzymatic resolution of (ꢁ)-5.
Dess–Martin oxidation of (ꢀ)-albicanol (5) derived from
(ꢀ)-6 gave an aldehyde (7), which was subjected to Julia
one-pot olefination using b-furylmethyl-heteroaromatic sul-
fones (8 or 9) gave (ꢀ)-trans coronarin E (2) and (ꢀ)-cis
coronarin E (12) with high cis-selectivity. Allylic oxidation
of (ꢀ)-trans coronarin E (2) followed by consecutive oxida-
tion and NaBH4 reduction gave (ꢀ)-coronarin A (1). Partial
reduction of (ꢀ)-cis coronarin E (12) provided (ꢀ)-(5S,
9S,10S)-15,16-epoxy-8(17),13(16),14-labdatriene (13), which
was subjected to allylic oxidation to provide (ꢀ)-austrocha-
parol (3). Consequently, absolute configurations of natural 3
3-Furylmethyl Benzothiazol-2-yl Sulfone (8) To a solution of 10
(10.67 g, 43.1 mmol) in CH2Cl2 (200 ml) was added m-chloroperbenzoic
acid (m-CPBA; 27.96 g, 129 mmol) at 0 °C and the whole mixture was
stirred for 2 h at rt. The reaction mixture was diluted with 2 M aqueous
NaOH and extracted with CH2Cl2. The organic layer was washed with brine,
and dried over MgSO4. The organic layer was evaporated to give a
crude residue, which was chromatographed on silica gel (200 g, n-
hexane : AcOEtꢄ10 : 1) to afford 8 (8.08 g, 67%) as colorless needles. 8: mp
134—136 °C (colorless needles from n-hexane–AcOEt); IR (KBr): 3141,
1555, 1504 cmꢂ1
;
1H-NMR d: 4.62 (2H, br s), 6.35 (1H, br s), 7.34—7.36
(2H, m), 7.59 (1H, ddd, Jꢄ8.0, 7.2, 1.2 Hz), 7.64 (1H, ddd, Jꢄ8.0, 7.2, 1.2

March 2008
401
Hz), 7.97 (1H, ddd, Jꢄ8.0, 1.2, 0.8 Hz), 8.24 (1H, ddd, Jꢄ8.0, 1.2, 0.8 Hz). (1H, dd, Jꢄ12.4, 2.8 Hz), 1.15—1.24 (1H, m), 1.34—1.44 (3H, m), 1.46—
13C-NMR d: 51.7, 111.1, 111.5, 122.3, 125.4, 127.7, 128.0, 136.9, 143.4,
1.53 (2H, m), 1.63—1.74 (1H, m), 2.06—2.14 (1H, m), 2.40 (1H, d, Jꢄ
143.8, 152.5, 165.0. Anal. Calcd for C12H9NO2S2: C, 51.60; H, 3.25; N, 10.4 Hz), 2.45 (1H, ddd, Jꢄ13.4, 4.4, 2.4 Hz), 4.53 (1H, q, Jꢄ2.0 Hz), 4.75
5.01. Found: C, 51.73; H, 3.37; N, 4.59.
(1H, q, Jꢄ2.0 Hz), 5.97 (1H, dd, Jꢄ15.8, 10.0 Hz), 6.19 (1H, d, Jꢄ15.6 Hz),
6.54 (1H, br s), 7.33—7.36 (2H, m). 13C-NMR d: 15.0, 19.1, 22.0, 23.4, 33.6
(2C), 36.8, 39.1, 40.8, 42.3, 54.8, 61.5, 107.6, 108.0, 121.7, 124.5, 128.3,
139.6, 143.2, 150.2. HR-MS (EI) Calcd for C20H28O2: 284.2140. Found:
3-Furylmethyl 1-Phenyl-1H-tetrazol-5-yl Sulfide (11) To a solution of
3-furylmethanol (1.00 g, 10.2 mmol) in THF (20 ml) was added 1-phenyl-
1H-tetrazol-5-thiol (3.65 g, 20.5 mmol), Ph3P (5.36 g, 20.4 mmol) and 2.2 M
diethylazodicarboxylate (DEAD) in toluene solution (7.0 ml, 15.4 mmol) at 284.2138.
0 °C and the whole mixture was stirred under argon atmosphere for 3 h at rt.
The reaction mixture was diluted with 2 M aqueous NaOH and extracted
(ꢀ)-(5S,9S,10S)-15,16-Epoxy-8(17),13(16),14-labdatriene (13) A mix-
ture of (ꢀ)-12 (0.300 g, 1.05 mmol), quinoline (0.05 g, 0.38 mmol) and 5%
with Et2O. The organic layer was washed with brine, and dried over MgSO4. Pd–BaSO4 (0.200 g) in MeOH (10.0 ml) was subjected to hydrogenation
The organic layer was evaporated to give a crude residue, which was chro- under hydrogen atmosphere for 3 d at ordinary temperature. The reaction
matographed on silica gel (100 g, n-hexane : AcOEtꢄ30 : 1) to afford 11 mixture was filtered with the aid of celite and filtrate was condensed to give
(2.38 g, 91%) as a pale yellow oil. 11: IR (neat): 3137, 3068, 1595, 1499 a residue which was chromatographed on silica gel (20.0 g, n-hexane) to
cmꢂ1; 1H-NMR d: 4.48 (2H, s), 6.23 (1H, dd, Jꢄ1.6, 0.4 Hz), 7.36 (1H, dd, provide (ꢀ)-13 (0.259 g, 86%) as a colorless oil. (ꢀ)-13: [a]D23 ꢀ44.1°
Jꢄ1.6, 1.6 Hz), 7.51—7.55 (6H, m). 13C-NMR d: 27.9, 110.7, 119.4, 123.7 (cꢄ0.59, CHCl3). IR (neat): 1644, 1564, 1496 cmꢂ1 1H-NMR (CDCl3) d:
.
(2C), 129.7 (2C), 130.1, 133.5, 141.4, 143.4, 153.7. HR-MS (EI) Calcd for 0.69 (3H, s), 0.80 (3H, s), 0.86 (3H, s), 0.97 (1H, dd, Jꢄ12.6, 4.0 Hz), 1.07
C12H10N4OS: 258.0565. Found: 258.0575.
3-Furylmethyl 1-Phenyl-1H-tetrazol-5-yl Sulfone (9) To a solution of
(1H, dd, Jꢄ12.8, 2.8 Hz), 1.16 (1H, dd, Jꢄ13.2, 4.0 Hz), 1.29—1.53 (3H,
m), 1.54—1.66 (3H, m), 1.69—1.79 (3H, m), 1.97 (1H, ddd, Jꢄ12.8, 12.8,
11 (0.201 g, 0.779 mmol) in CH2Cl2 (3.5 ml) was added m-chloroperbenzoic 5.2 Hz), 2.19—2.28 (1H, m), 2.40 (1H, ddd, Jꢄ12.6, 3.8, 2.0 Hz), 2.55 (1H,
acid (m-CPBA; 0.836 g, 4.84 mmol) at 0 °C and the whole mixture was ddd, Jꢄ14.0, 10.0, 2.8 Hz), 4.56 (1H, s), 4.86 (1H, s), 6.26 (1H, br s), 7.19
stirred for 15 h at rt. The reaction mixture was diluted with 2 M aqueous
NaOH and extracted with CH2Cl2. The organic layer was washed with brine, 33.6 (2C), 38.3, 39.0, 39.6, 42.1, 55.5, 56.1, 106.2, 111.0, 125.6, 138.7,
and dried over MgSO4. The organic layer was evaporated to give a 142.6, 148.5. HR-MS (EI) Calcd for C20H30O2: 286.2297. Found: 286.2300.
(1H, br s), 7.34 (1H, br s). 13C-NMR d: 14.5, 19.4, 21.7, 23.6, 24.0, 24.4,
crude residue, which was chromatographed on silica gel (200 g, n-
hexane : AcOEtꢄ5 : 1) to afford 9 (0.069 g, 31%) as colorless needles. 9: mp
(ꢀ)-Austrochaparol (3) To a solution of (ꢀ)-13 (0.050 g, 0.175 mmol)
in CH2Cl2 (1.50 ml) was added SeO2 (0.160 g, 1.43 mmol) at 0 °C and the
138—140 °C (colorless needles from n-hexane–AcOEt); IR (KBr): 3121, whole mixture was stirred for 12 h at rt. The reaction mixture was diluted
1
3070, 1601, 1497 cmꢂ1; H-NMR d: 4.84 (2H, s), 6.43 (1H, dd, Jꢄ2.0, 0.8 with saturated Na2S2O3 and extracted with AcOEt. The organic layer was
Hz), 7.40 (1H, dd, Jꢄ1.6, 1.6 Hz), 7.48—7.63 (6H, m). 13C-NMR d: 53.3, washed with brine and dried over MgSO4. Removal of the organic solvent
109.7, 111.7, 125.1 (2C), 129.5 (2C), 131.4, 132.8, 143.9, 144.2, 152.7. gave a crude residue, which was chromatographed on silica gel (5.00 g, n-
Anal. Calcd for C12H10N4O3S: C, 49.65; H, 3.47; N, 19.30. Found: C, 49.85; hexane : AcOEtꢄ10 : 1) to afford (ꢀ)-3 (0.026 g, 50%) as a colorless oil.
H, 3.58; N, 19.48.
(ꢀ)-trans-Coronarin E (2) and (ꢀ)-cis-Coronarin E (12) 1) A sus- (CDCl3) d: 0.67 (3H, s), 0.80 (3H, s), 0.88 (3H, s), 1.05 (1H, ddd, Jꢄ17.0,
pension of (ꢀ)-6 (4.50 g, 17.0 mmol) and K2CO3 (8.36 g, 60.5 mmol) in 13.0, 4.0 Hz), 1.21 (1H, ddd, Jꢄ17.0, 13.0, 4.0 Hz), 1.35—1.65 (7H, m),
(ꢀ)-3: [a]D27 ꢀ5.6° (cꢄ0.50, CHCl3). IR (KBr): 3330 cmꢂ1 1H-NMR
.
MeOH (50.0 ml) was stirred for 12 h at rt. The reaction mixture was evapo- 1.70—1.84 (2H, m), 1.84—1.90 (1H, m), 2.17 (1H, dd, Jꢄ10.0, 1.3 Hz),
rated, diluted with saturated brine and extracted with Et2O. The organic layer 2.20—2.29 (1H, m), 2.53 (1H, ddd, Jꢄ14.2, 10.0, 4.0 Hz), 4.40 (1H, br s),
was dried over MgSO4 and evaporated to afford a crude product which was 4.70 (1H, dd, Jꢄ1.3, 1.1 Hz), 5.09 (1H, dd, Jꢄ1.1, 1.1 Hz), 6.27 (1H, d, Jꢄ
chromatographed on silica gel (100.0 g) to give (ꢀ)-5 (3.78 g, 99% yield)
from n-hexane : AcOEtꢄ30 : 1 eluent. (ꢀ)-5: mp 71—73 °C (colorless nee-
1.0 Hz), 7.20 (1H, dd, Jꢄ1.1, 1.1 Hz), 7.35 (1H, dd, Jꢄ1.6, 1.6 Hz). 13C-
NMR d: 13.5, 19.4, 21.5, 23.4, 23.7, 31.0, 33.1, 33.3, 38.8, 39.8, 42.1, 47.6,
dles from n-hexane), [a]D24 ꢀ10.8° (cꢄ0.5, CHCl3, corresponds to ꢃ98% 50.4, 74.2, 109.7, 110.9, 125.4, 138.7, 142.7, 149.6. HR-MS (EI) Calcd for
1
ee), H-NMR data of (ꢀ)-5 were identical with those of the reported (ꢀ)-
C20H30O2: 302.2246. Found: 302.2244.
(ꢁ)-epi-Coronarin A (14) To a solution of (ꢀ)-2 (0.050 g, 0.176 mmol)
5.10 Anal. Calcd for C15H22O: C, 81.02; H, 11.79. Found: C, 81.19; H, 11.97.
2) To a solution of (ꢀ)-5 (1.00 g, 4.49 mmol) in CH2Cl2 (65.0 ml) was added in CH2Cl2 (1.50 ml) was added SeO2 (0.039 g, 0.252 mmol) at 0 °C and the
NaHCO3 (5.89 g, 70.1 mmol) and Dess–Martin reagent (3.15 g, 7.43 mmol)
at 0 °C and the reaction mixture was stirred for 2 h at rt. The reaction mix-
whole mixture was stirred for 30 min at 0 °C. The reaction mixture was di-
luted with brine and extracted with CH2Cl2. The organic layer was dried over
ture was directly subjected to chromatography on silica gel (100 g, n- MgSO4. Removal of the organic solvent gave a crude residue, which was
hexane : AcOEtꢄ200 : 1) to give 7 (0.823 g, 83% yield) as a colorless oil. 7; chromatographed on silica gel (5.00 g, n-hexane : AcOEtꢄ20 : 1) to afford
1H-NMR (CDCl3) d: 0.87 (3H, s), 0.89 (3H, s), 1.03 (1H, dd, Jꢄ12.6, 2.8 (ꢂ)-14 (0.025 g, 47%) as a colorless oil. (ꢂ)-14: [a]D23 ꢂ13.4° (cꢄ1.16,
Hz), 1.15 (3H, s), 1.17—1.28 (2H, m), 1.38—1.50 (3H, m), 1.54—1.66 (2H, CHCl3). IR (neat): 3390, 1647 cmꢂ1. 1H-NMR (CDCl3) d: 0.81 (3H, s), 0.83
m), 1.69—1.75 (1H, m), 2.05—2.13 (1H, m), 2.37—2.49 (2H, m), 4.50 (1H, (3H, s), 0.90 (3H, s), 1.03—1.13 (1H, m), 1.16—1.28 (2H, m), 1.37—1.67
br s), 4.92 (1H, br s), 9.87 (1H, d, Jꢄ4.8 Hz). 13C-NMR d: 16.0, 18.7, 21.9, (6H, m), 1.81—1.91 (1H, m), 2.88 (1H, d, Jꢄ10.0 Hz), 4.38—4.42 (1H, m),
23.1, 33.4, 33.5, 36.7, 39.0, 39.9, 41.9, 54.0, 67.9, 109.2, 145.0, 205.7. 3) To 4.69 (1H, dd, Jꢄ1.6, 1.6 Hz), 4.98 (1H, dd, Jꢄ1.6, 1.6 Hz), 5.90 (1H, dd, Jꢄ
a solution of 8 (1.14 g, 4.09 mmol) in THF (15.0 ml) was added 1.0 M solu-
15.8, 10.0 Hz), 6.24 (1H, d, Jꢄ15.8 Hz), 6.50—6.53 (1H, m), 7.31—7.37
tion of lithium bis(trimethylsilylamide) in toluene (4.10 ml, 4.10 mmol) at (2H, m). 13C-NMR d: 14.0, 19.0, 21.7, 30.0, 33.1, 33.2, 39.4, 40.4, 42.2,
ꢂ78 °C under argon atmosphere. After being stirred at ꢂ78 °C for 20 min, 7 46.9, 56.0, 73.4, 107.5, 111.8, 122.4, 124.3, 127.2, 139.7, 143.3, 151.3. HR-
(0.819 g, 3.72 mmol) in THF (5 ml) was slowly added. The mixture was MS (EI) Calcd for C20H28O2: 300.2089. Found: 300.2082.
stirred for 0.5 h at ꢂ78 °C. The reaction was diluted with brine and extracted
(ꢀ)-Coronarin A (1) To a solution of (ꢂ)-14 (0.009 g, 0.03 mmol) in
with Et2O. The organic layer was washed with brine and dried over MgSO4.
CH2Cl2 (1.00 ml) was added Dess–Martin reagent (0.038 g, 0.09 mmol) at
The organic layer was evaporated to give a crude residue, which was chro- 0 °C and the whole mixture was stirred for 1 h at the same temperature. The
matographed on silica gel (100 g, n-hexane) to afford (ꢀ)-12 (0.814 g, 77%)
and (ꢀ)-2 (0.116 g, 11%) in elution order.
reaction mixture was filtered and the filtrate was condensed to give a crude
15, which was used for the next reaction without further purification. To a
(ꢀ)-12 (Colorless Oil): [a]D23 ꢀ109.1° (cꢄ0.44, CHCl3). IR (neat): 1644 solution of the above 15 in MeOH (1.00 ml) was added NaBH4 (0.001 g,
1
cmꢂ1. H-NMR (CDCl3) d: 0.84 (3H, s), 0.86 (3H, s), 0.87 (3H, s), 0.91— 0.03 mmol) at 0 °C and the whole mixture was stirred for 20 min at the same
0.95 (1H, m), 1.11 (1H, dd, Jꢄ12.5, 2.8 Hz), 1.14—1.22 (1H, m), 1.35— temperature. The reaction mixture was diluted with saturated NaHCO3 and
1.42 (3H, m), 1.47—1.54 (1H, m), 1.55—1.57 (1H, m), 1.70—1.72 (1H, m), extracted with Et2O. The organic layer was dried over MgSO4. Removal of
2.06—2.14 (1H, m), 2.50 (1H, ddd, Jꢄ13.4, 4.4, 2.3 Hz), 2.81 (1H, d, Jꢄ the organic solvent gave a residue, which was chromatographed on silica gel
10.0 Hz), 4.61 (1H, dd, Jꢄ3.7, 2.0 Hz), 4.75 (1H, dd, Jꢄ3.7, 2.0 Hz), 5.62
(1H, dd, Jꢄ11.8, 9.4 Hz), 6.32 (1H, d, Jꢄ12.0 Hz), 6.34 (1H, t, Jꢄ1.2 Hz),
(3.00 g, n-hexane : AcOEtꢄ20 : 1) to provide (ꢀ)-1 (0.007 g, 78%) as a col-
orless oil. (ꢀ)-1: mp 99—101 °C (colorless needles from n-hexane), [a]D23
1
7.32 (1H, t, Jꢄ1.2 Hz), 7.34 (1H, t, Jꢄ1.2 Hz). 13C-NMR d: 14.3, 19.0, ꢀ26.9° (cꢄ0.35, CHCl3). IR (neat): 3351, 1650 cmꢂ1. H-NMR (CDCl3) d:
21.9, 23.4, 33.4 (2C), 36.4, 39.0, 39.9, 42.1, 54.9, 57.0, 108.4, 111.0, 120.7, 0.85 (3H, s), 0.85 (3H, s), 0.93 (3H, s), 0.93—1.04 (1H, m), 1.13—1.56
122.2, 130.0, 140.7, 142.4, 148.0. HR-MS (EI) Calcd for C20H28O2: (7H, m), 1.82 (1H, br s), 2.10 (1H, ddd, Jꢄ12.0, 5.6, 2.4 Hz), 2.35 (1H, d,
284.2140. Found: 284.2145. (ꢀ)-2: mp 94—96 °C (colorless needles from
Jꢄ9.6 Hz), 4.10 (1H, dd, Jꢄ11.2, 5.6 Hz), 4.74 (1H, s), 5.13 (1H, s), 5.99
(1H, dd, Jꢄ15.6, 9.6 Hz), 6.21 (1H, d, Jꢄ15.6 Hz), 6.55 (1H, s), 7.37 (2H,
n-hexane). [a]D20 ꢀ22.4° (cꢄ1.4, CHCl3). IR (neat): 1643 cmꢂ1 1H-NMR
.
(CDCl3) d: 0.84 (3H, s), 0.85 (3H, s), 0.90 (3H, s), 1.02—1.07 (1H, m), 1.11 m). 13C-NMR d: 15.0, 19.0, 21.9, 33.1, 33.5 (2C), 39.1, 40.3, 42.0, 52.5,

402
Vol. 56, No. 3
59.7, 73.3, 104.8, 107.6, 122.2, 124.3, 126.9, 139.8, 143.3, 152.1. HR-MS layer was evaporated to give a crude residue, which was chromatographed
(EI) Calcd for C20H28O2: 300.2089. Found: 300.2080.
on silica gel (10 g, n-hexane : AcOEtꢄ10 : 1) to afford (ꢀ)-20 (0.186 g,
(ꢀ)-(1R,4aS,8aS)-Decahydro-5,5,8a-trimethyl-2-methylene-1-naph- 97%) as colorless needles (n-hexane). (ꢀ)-20: mp 69 °C; [a]D27 ꢀ20.8° (cꢄ
1
thaleneacetonitrile (16) To a solution of (ꢀ)-5 (0.60 g, 2.7 mmol) in
toluene (10 ml) was added acetone cyanohydrin (2.5 ml, 27 mmol), Ph3P 0.67 (3H, s), 0.82 (3H, s), 0.91 (3H, s), 0.93 (9H, s), 1.13 (1H, dd, Jꢄ12.9,
(1.1 g, 4.1 mmol) and diisopropylazodicarboxylate (DIAD, 0.8 ml, 4.1 mmol) 2.3 Hz), 1.21 (1H, dd, Jꢄ11.9, 6.3 Hz), 1.24—1.37 (2H, m), 1.42—1.49
0.75, CHCl3); IR (KBr): 2245 cmꢂ1; H-NMR d: 0.09 (3H, s), 0.10 (3H, s),
and the mixture was stirred for 1 d at 70 °C. The reaction mixture was di-
(1H, m), 1.51—1.62 (2H, m), 1.95 (1H, ddd, Jꢄ12.6, 5.5, 2.5 Hz), 2.03—
luted with water (ice) and extracted with AcOEt. The organic layer was 2.10 (1H, m), 2.39 (1H, dd, Jꢄ16.9, 10.6 Hz), 2.55 (1H, dd, Jꢄ16.7, 4.3
washed with brine and dried over MgSO4. Evaporation of the organic sol- Hz), 3.98 (1H, dd, Jꢄ10.8, 5.3 Hz), 4.73 (1H, br s), 5.37 (1H, br s). 13C-
vent gave a crude oil, which was chromatographed on silica gel (40 g, n- NMR d: ꢂ4.8, ꢂ4.7, 13.9, 14.1, 18.6, 19.2, 21.8, 26.0 (3C), 33.4, 33.5,
hexane : AcOEtꢄ19 : 1) to afford a nitrile (16) (0.400 g, 64%) as colorless
34.1, 39.1, 39.2, 41.7, 51.6, 52.6, 74.0, 105.6, 119.8, 147.8. Anal. Calcd for
1
plates (n-hexane). H- and 13C-NMR data of the synthetic 16 were identical C22H39NOSi: C, 73.07; H, 10.87; N, 3.87. Found: C, 73.04; H, 11.02; N,
with those of the reported (ꢀ)-16.15)
3.64. MS (FAB) m/z: 384 (MꢀꢀNa).
(ꢀ)-(1R,3S,4aS,8aS)-Decahydro-5,5,8a-trimethyl-3-hydroxy-2-methyl-
(ꢁ)-(1R,3R,4aS,8aS)-Decahydro-5,5,8a-trimethyl-3-tert-butyl-
ene-1-naphthaleneacetonitrile (17) To
1 mmol) in CH2Cl2 (5 ml) was added 5.5 M tert-BuOOH in decane solution
a
solution of SeO2 (0.111 g, dimethylsiloxy-2-methylene-naphthaleneacetoaldehyde (21) To a solu-
tion of (ꢀ)-20 (0.185 g, 0.51 mmol) in toluene (1.5 ml) was added 1 M di-
(0.73 ml, 4 mmol) and the mixture was stirred for 1 h at rt. A solution of 16 isobutylaluminum hydride (Dibal) in toluene solution (0.6 ml, 0.6 mmol) at
(0.462 g, 2 mmol) in CH2Cl2 (1 ml) was added to the above solution and the ꢂ78 °C and the reaction mixture was stirred for 30 min at at ꢂ78 °C. To the
whole mixture was stirred for 1 d at rt. The reaction mixture was diluted
with saturated Na2S2O3 solution and extracted with AcOEt. The organic
reaction mixture was added acetone (0.2 ml) at 0 °C. The reaction mixture
was acidified with 2 M HCl solution and extracted with Et2O. The organic
layer was washed with brine and dried over MgSO4. The organic layer was layer was washed with brine, and dried over MgSO4. The organic layer was
evaporated to give a crude residue, which was chromatographed on silica gel evaporated to give a crude residue, which was chromatographed on silica gel
(40 g, n-hexane : AcOEtꢄ3 : 1) to afford (ꢂ)-17 (0.392 g, 79%). Recrystal-
lization of (ꢂ)-17 from n-hexane gave colorless needles. (ꢂ)-17: mp 149— less oil. (ꢂ)-21: [a]D24 ꢂ14.7° (cꢄ1.02, CHCl3); IR (KBr): 1726 cmꢂ1; H-
150 °C; [a]D23 ꢂ24.9° (cꢄ0.83, CHCl3); IR (KBr): 3445, 2259 cmꢂ1 1H- NMR d: 0.069 (3H, s), 0.076 (3H, s), 0.70 (3H, s), 0.82 (3H, s), 0.91 (3H,
NMR d: 0.67 (3H, s), 0.82 (3H, s), 0.91 (3H, s), 1.18—1.29 (2H, m), 1.38— s), 0.93 (9H, s), 1.00—1.09 (1H, m), 1.14—1.27 (1H, m), 1.28—1.40 (1H,
1.48 (1H, m), 1.51—1.62 (5H, m), 1.71 (1H, dd, Jꢄ13.6, 3.0 Hz), 1.91 (1H, m), 1.40—1.61 (3H, m), 1.96 (1H, ddd, Jꢄ12.6, 5.5, 2.0 Hz), 2.27 (1H, dd,
ddd, Jꢄ13.6, 2.5, 2.5 Hz), 2.30 (1H, dd, Jꢄ16.6, 10.8 Hz), 2.58 (1H, dd, Jꢄ Jꢄ10.6, 4.0 Hz), 2.45 (1H, ddd, Jꢄ16.6, 4.0, 1.0 Hz), 2.55 (1H, ddd,
(10 g, n-hexane : AcOEtꢄ20 : 1) to afford (ꢂ)-21 (0.163 g, 87%) as a color-
1
;
16.6, 3.8 Hz), 2.73 (1H, ddd, Jꢄ19.9, 1.9, 2.0 Hz), 4.43 (1H, br s), 4.77 (1H,
Jꢄ16.9, 10.6, 3.0 Hz), 3.98 (1H, dd, Jꢄ11.1, 5.5 Hz), 4.54 (1H, br s), 5.24
d, Jꢄ1.8 Hz), 5.18 (1H, d, Jꢄ1.5 Hz). 13C-NMR d: 13.0, 13.8, 19.2, 21.6,
(1H, br s), 9.63 (1H, dd, Jꢄ3.5, 1.0 Hz). 13C-NMR d: ꢂ4.8, ꢂ4.7, 14.7,
30.3, 33.1, 33.3, 38.9, 39.6, 41.8, 47.2, 47.9, 73.2, 110.6, 119.8, 147.8. MS 18.6, 19.4, 21.8, 26.0 (3C), 33.5 (2C), 34.3, 38.7, 39.4, 39.7, 42.0, 49.3,
(FAB) m/z: 248 (Mꢀꢀ1), 230 (Mꢀꢀ1-H2O).
(ꢀ)-(1R,3R,4aS,8aS)-Decahydro-5,5,8a-trimethyl-3-benzoyloxy-2- 11.06. Found: C, 72.39; H, 10.99. MS (FAB) m/z: 387 (MꢀꢀNa).
methylene-1-naphthaleneacetonitrile (18) To solution of (ꢂ)-17 Horner–Emmons Condensation of (ꢁ)-21 and Diethoxyphosphonobuty-
(0.209 g, 0.84 mmol) in THF (6 ml) was added benzoic acid (0.642 g, rolactone To solution of diethoxyphosphonobutyrolactone (0.510 g,
53.1, 74.4, 105.8, 149.8, 202.7. Anal. Calcd for C22H40O2Si: C, 72.46; H,
a
a
5.3 mmol), Ph3P (1.324 g, 5.1 mmol) and 49% diethylazodicarboxylate in 2.3 mmol) in DMSO (2.5 ml) was added t-BuOK (0.213 g, 1.9 mmol) and
toluene solution (2.2 ml, 5.1 mmol) at 0 °C and the whole mixture was the reaction mixture was stirred for 30 min at rt. To a solution of (ꢂ)-21
stirred for 1 h at 0 °C. The reaction mixture was diluted with 7% aqueous
(0.163 g, 0.44 mmol) in DMSO (0.5 ml) was added the above ylide solution
NaHCO3 and extracted with Et2O. The organic layer was washed with at rt and the whole mixture was stirred for 30 min at rt. The reaction mixture
brine, and dried over MgSO4. The organic layer was evaporated to give a was diluted with brine and extracted with Et2O. The organic layer was dried
crude residue, which was chromatographed on silica gel (40 g, n-hexane : over MgSO4. The organic layer was evaporated to give a crude residue,
AcOEtꢄ5 : 1) to afford (ꢀ)-18 (0.234 g, 79%) as colorless prisms (n- which was chromatographed on silica gel (15 g, n-hexane : AcOEtꢄ5 : 1) to
hexane/AcOEt). (ꢀ)-18: mp 150—151 °C; [a]D25 ꢀ89.7° (cꢄ0.95, CHCl3);
afford the less polar (ꢀ)-22 (0.053 g, 27%) as a colorless amorphous solid
1
IR (KBr): 3349 cmꢂ1; H-NMR d: 0.78 (3H, s), 0.85 (3H, s), 0.94 (3H, s), and the more polar (ꢀ)-23 (0.122 g, 63%) as colorless needles (n-hexane).
1.16—1.29 (3H, m), 1.32 (1H, dd, Jꢄ13.1, 2.5 Hz), 1.45—1.68 (4H, m),
(ꢀ)-22: mp 104 °C; [a]D24 ꢀ21.8° (cꢄ1.0, CHCl3); IR (KBr): 1745,
2.18—2.27 (2H, m), 2.44 (1H, dd, Jꢄ16.6, 10.0 Hz), 2.61 (1H, dd, Jꢄ16.6, 1660 cmꢂ1; 1H-NMR d: 0.069 (3H, s), 0.082 (3H, s), 0.72 (3H, s), 0.81 (3H,
4.6 Hz), 4.82 (1H, br s), 5.31 (1H, br s), 5.46 (1H, dd, Jꢄ16.6, 5.5 Hz), 7.47
s), 0.88 (3H, s), 0.93 (9H, s), 1.00—1.22 (3H, m), 1.24—1.38 (2H, m),
(2H, t, Jꢄ7.6 Hz), 7.59 (1H, t, Jꢄ7.5 Hz), 8.13 (2H, d, Jꢄ7.7 Hz). 13C-NMR 1.38—1.45 (1H, m), 1.46—1.56 (1H, m), 1.66 (1H, d, Jꢄ10.6 Hz), 1.74—
d: 13.9, 14.0, 19.1, 21.7, 30.1, 33.5, 33.6, 39.0, 39.2, 41.6, 51.5, 52.4, 74.3, 1.81 (1H, m), 1.93 (1H, ddd, Jꢄ12.1, 5.0, 2.0 Hz), 2.69—2.79 (1H, m),
105.7, 119.3, 128.3 (2C), 129.5 (2C), 130.1, 132.9, 143.8, 165.0. Anal.
Calcd for C23H29NO2: C, 78.59; H, 8.32; N, 3.98. Found: C, 78.39; H, 8.51; 4.26—4.34 (2H, m), 4.52 (1H, d, Jꢄ1.5 Hz), 5.25 (1H, d, Jꢄ1.5 Hz), 6.01—
N, 3.50. MS (FAB) m/z: 352 (Mꢀꢀ1). 6.18 (1H, m). 13C-NMR d: ꢂ4.7 (2C), 14.5, 18.7, 19.4, 21.8, 22.9, 26.1
(ꢀ)-(1R,3R,4aS,8aS)-Decahydro-5,5,8a-trimethyl-3-hydroxy-2-methyl- (3C), 29.2, 33.5, 33.6, 34.6, 39.0, 39.4, 42.0, 53.2, 55.5, 65.3, 74.9, 105.3,
ene-1-naphthaleneacetonitrile (19) mixture of (ꢀ)-18 (0.160 g, 122.9, 144.6, 149.4, 170.0. Anal. Calcd for C26H44O3Si: C, 72.17; H, 10.25.
2.84—2.91 (2H, m), 2.97—3.07 (1H, m), 3.91 (1H, dd, Jꢄ11.1, 5.0 Hz),
A
0.46 mmol) and K2CO3 (0.077 g, 0.55 mmol) in MeOH (2 ml) was stirred for
3 h at rt. The reaction mixture was diluted with 7% aqueous NaHCO3 and
Found: C, 71.74; H, 10.15. HR-MS (EI) m/z: Calcd for C26H44O3Si:
432.3060. Found: 432.3050. (ꢀ)-23: mp 97 °C; [a]D24 ꢀ7.0° (cꢄ1.0,
1
extracted with Et2O. The organic layer was washed with brine, and dried CHCl3); IR (KBr): 1745, 1660 cmꢂ1; H-NMR d: 0.070 (3H, s), 0.083 (3H,
over MgSO4. The organic layer was evaporated to give a crude residue, s), 0.71 (3H, s), 0.82 (3H, s), 0.90 (3H, s), 0.93 (9H, s), 0.96—1.80 (9H, m),
which was chromatographed on silica gel (10 g, n-hexane : AcOEtꢄ5 : 1) to 1.94 (1H, ddd, Jꢄ12.6, 5.6, 2.5 Hz), 2.22—2.44 (2H, m), 2.80—2.96 (2H,
afford (ꢀ)-19 (0.088 g, 78%) as colorless plates (n-hexane/AcOEt). (ꢀ)-19: m), 3.92 (1H, dd, Jꢄ11.1, 5.5 Hz), 4.38 (2H, t-like), 4.52 (1H, d, Jꢄ1.0 Hz),
mp 107—108 °C; [a]D23 ꢀ35.3° (cꢄ0.92, CHCl3); IR (KBr): 3425, 2260
5.26 (1H, d, Jꢄ1.5 Hz), 6.68 (1H, ddd, Jꢄ9.9, 6.5, 3.0 Hz). 13C-NMR d:
1
cmꢂ1; H-NMR d: 0.68 (3H, s), 0.83 (3H, s), 0.93 (3H, s), 1.07—1.34 (5H, ꢂ4.7 (2C), 14.5, 18.6, 19.4, 21.8, 24.4, 25.6, 26.1 (3C), 33.5 (2C), 34.4,
m), 1.43—1.49 (1H, m), 1.51—1.62 (2H, m), 1.79 (1H, d, Jꢄ5.0 Hz),
39.2, 39.3, 42.0, 53.0, 54.4, 65.3, 74.5, 105.2, 124.6, 141.6, 149.3, 170.9.
2.06—2.17 (2H, m), 2.41 (1H, dd, Jꢄ16.6, 10.6 Hz), 2.59 (1H, dd, Jꢄ16.6, Anal. Calcd for C26H44O3Si: C, 72.17; H, 10.25. Found: C, 72.10; H, 10.32.
4.0 Hz), 4.07 (1H, dd, Jꢄ11.0, 5.0 Hz), 4.81 (1H, br s), 5.34 (1H, br s). 13C- MS (FAB) m/z: 455 (MꢀꢀNa).
NMR d: 13.8, 13.9, 19.1, 21.6, 33.1, 33.4 (2C), 38.9, 39.0, 41.5, 51.3, 52.4,
72.8, 104.7, 119.7, 148.2. Anal. Calcd for C16H25NO: C, 77.68; H, 10.19; N, a mixed solvent [MeOH (2 ml)/THF (0.5 ml)] was added 10-camphorsufonic
5.66. Found: C, 77.71; H, 10.28; N, 5.33. MS (FAB) m/z: 270 (MꢀꢀNa).
acid (CSA; 0.073 g, 0.32 mmol) at rt and the reaction mixture was stirred for
(ꢀ)-Pacovatinin A (4) To a solution of (ꢀ)-23 (0.091 g, 0.21 mmol) in
(ꢀ)-(1R,3R,4aS,8aS)-Decahydro-5,5,8a-trimethyl-3-tert-butyl- 6 h rt. The reaction mixture was diluted with 7% aqueous NaHCO3 and ex-
dimethylsiloxy-2-methylene-naphthaleneacetonitrile (20) A mixture of tracted with Et2O. The organic layer was washed with brine, and dried over
(ꢀ)-19 (0.131 g, 0.53 mmol), tert-butyldimethylsilyl chloride (TBDMSCl; MgSO4. The organic layer was evaporated to give a crude residue, which
0.123 g, 0.82 mmol) and imidazole (0.063 g, 0.92 mmol) in DMF (1.5 ml)
was stirred for 1 h at rt. The reaction mixture was diluted with brine and ex-
was chromatographed on silica gel (5 g, n-hexane : AcOEtꢄ2 : 1) to afford
(ꢀ)-4 (0.062 g, 92%) as a colorless amorphous solid. (ꢀ)-4: mp 146—
tracted with Et2O. The organic layer was dried over MgSO4. The organic 147 °C; [a]D24 ꢀ12.8° (cꢄ1.0, CHCl3); IR (KBr): 3266, 1747, 1677 cmꢂ1
;

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1H-NMR d: 0.72 (3H, s), 0.83 (3H, s), 0.92 (3H, s), 1.05 (1H, ddd, Jꢄ12.6,
12.6, 4.0 Hz), 1.17 (1H, dd, Jꢄ12.6, 2.5 Hz), 1.21—1.35 (2H, m), 1.41—
1.48 (1H, m), 1.48—1.64 (2H, m), 1.71 (1H, br d, Jꢄ5.0 Hz), 1.80 (1H, br d,
Jꢄ8.1 Hz), 2.11 (1H, ddd, Jꢄ11.6, 5.6, 2.5 Hz), 2.23—2.34 (1H, m), 2.35—
2.45 (1H, m), 2.84—2.92 (2H, m), 4.00 (1H, ddd, Jꢄ10.8, 5.3, 5.3 Hz), 4.39
(2H, t-like), 4.52 (1H, br s), 5.20 (1H, br s), 6.68 (1H, ddd, Jꢄ10.1, 6.8,
3.0 Hz). 13C-NMR d: 14.3, 19.3, 21.6, 25.2, 25.2, 33.5, 33.5, 33.5, 39.1,
39.2, 41.8, 53.0, 54.4, 65.3, 73.6, 104.2, 124.9, 141.5, 150.1, 171.2. Anal.
Calcd for C20H30O3·0.5H2O: C, 73.36; H, 9.54. Found: C, 73.87; H, 9.24.
HR-MS (EI) m/z: Calcd for C20H30O3: 318.2195. Found: 318.2198.
5) Amano Y., Kinoshita M., Akita H., J. Mol. Catalysis B: Enzymatic, 32,
141—148 (2005).
6) Oh S., Jeong I. H., Shin W-S., Lee S., Bioorg. Med. Chem. Lett., 13,
2009—2012 (2003).
7) Review: Blakemore P. R., J. Chem. Soc. Perkin Trans. 1, 2002, 2563—
2585 (2002).
8) Maria K., Maria L., Valentine R., Tetrahedron, 61, 2003—2010
(2005).
9) Jung M., Ko I., Lee S., J. Nat. Prod., 61, 1394—1396 (1998).
10) Akita H., Amano Y., Kato K., Nozawa M., Tetrahedron: Asymmetry,
15, 725—732 (2004).
11) Matsuda H., Morikawa T., Sakamoto Y., Toguchida I., Yoshikawa M.,
Heterocycles, 56, 45—56 (2002).
12) Morikawa T., Matsuda H., Sakamoto Y., Ueda K., Yoshikawa M.,
Chem. Pharm. Bull., 50, 1045—1049 (2002).
References and Notes
1) Itokawa H., Morita H., Katou I., Takya K., Cavalheiro A. J., de
Oliveira R. C. B., Ishige M., Motidome M., Planta Medica, 1988,
311—315 (1988).
13) Tsunoda T., Uemoto K., Nagin C., Kawamura M., Kaku H., Ito S.,
Tetrahedron Lett., 40, 7355—7358 (1999).
2) Itokawa H., Morita H., Takya K., Motidome M., Chem. Pharm. Bull.,
36, 2682—2684 (1988).
14) Micheal T. C., Franck C., J. Am. Chem. Soc., 128, 3128—3129 (2006).
15) Kinoshita M., Ohtsuka M., Nakamura D., Akita H., Chem. Pharm.
Bull., 50, 930—934 (2002).
3) Bohlmann F., Zdero C., Gupta R. K., King R. M., Robinson H., Phyto-
chemistry, 19, 2695—2705 (1980).
4) Sekiguchi M., Shigenori H., Ohsaki A., Kobayashi J., J. Nat. Prod., 64,
1102—1106 (2001).
16) Mitsunobu O., Synthesis, 1981, 1—28 (1981).