First synthesis of (+)-α- and (+)-γ-Polypodatetraenes

Article abstract of DOI:10.1248/cpb.50.930

First synthesis of (+)-α-polypodatetraene (1) and (+)-γ-polypodatetraene (2) was achieved from (+)-albicanol (6) and (2)-drimenol (8), respectively. The absolute structure of natural (+)-2 was established to be (5S,9S,10S)-polypoda-7,13(E),17(E),21-tetrae

Full text of DOI:10.1248/cpb.50.930

930
Chem. Pharm. Bull. 50(7) 930—934 (2002)
Vol. 50, No. 7
a
g
First Synthesis of (؉)- - and (؉)- -Polypodatetraenes
Masako KINOSHITA, Mahisa OHTSUKA, Daisuke NAKAMURA, and Hiroyuki AKITA*
School of Pharmaceutical Sciences, Toho University; 2–2–1 Miyama, Funabashi, Chiba 274–8510, Japan.
Received February 12, 2002; accepted March 20, 2002
First synthesis of (؉)-a-polypodatetraene (1) and (؉)-g-polypodatetraene (2) was achieved from (؉)-albi-
canol (6) and (؊)-drimenol (8), respectively. The absolute structure of natural (؉)-2 was established to be
(5S,9S,10S)-polypoda-7,13(E),17(E),21-tetraene.
Key words (ϩ)-a-polypodatetraene; (ϩ)-g-polypodatetraene; total synthesis
Polypodanes constitute a new class of bicyclic triter- mide (CBr4) and triphenylphosphine (Ph3P) under neutral
penoids and their occurrence in nature is important for the conditions gave the corresponding bromide 14, which was
mechanistic study of the biosynthesis of polycyclic triter- treated with NaCN in DMSO to provide the nitrile 15 in 71%
penoids. (ϩ)-a-Polypodatetraene (1) and (ϩ)-g-polypodate- overall yield. Dibal-H reduction of 15 yielded an aldehyde 16
traene (2) are the first compound of this class and were iso- (82%), which was reacted with (carbethoxyethylidene)tri-
lated from the fresh leaves of Polypodium fauriei and phenylphosphorane to give selectively (E)-17 in quantitative
Lemmaphyllum microphyllum for (1), and Polystichum yield. Dibal-H reduction of (E)-17 gave an allyl alcohol 18 in
ovatopaleaceum and P. polyblephalum for (2), respectively.1) quantitative yield, which was treated with tosyl chloride to
Their planar structures were established to be polypoda- afford the allyl chloride 19 in 43% yield. The prepared 19
8(26),13,17,21-tetraene (1) and polypoda-7,13,17,21-tetraene was immediately treated with sodium benzene sulfinate
1
(2) by a careful analysis of H-, 13C-NMR, IR, and mass- (PhSO2Na·2H2O) to provide the sulfone 20 in 93% yield.
spectral data.1) The absolute structure of the natural (ϩ)-a- The sulfone 20 was treated with lithium diisopropylamide
polypodatetraene (ϩ)-1 is determined as depicted in 1 be- (LDA) to provide the corresponding carbanion, which was
cause the optical rotation shows opposite signs, [a]D ϩ27.4° treated with trans-geranyl bromide to furnish the alkylated
for the natural (ϩ)-1 and [a]D Ϫ18.9° for the synthetic ent-1 product 21 in 56% yield. Reductive elimination of phenylsul-
derived from copalic acid (3).2) On the other hand, the ab- fonyl group in 21 using sodium-amalgam (5% Na–Hg) gave
solute structure of the natural (ϩ)-g-polypodatetraene (2) the synthetic (ϩ)-1 ([a]D ϩ29.6° (cϭ0.22, CHCl3)) in 42%
was assumed by comparison of optical rotation between 1, 2 yield, which was consistent with the natural (ϩ)-1 ([a]D
([a]D ϩ8.7°) and a-onoceradiene (4) ([a]D ϩ22.4°), ono- ϩ27.4° (cϭ0.4, CHCl3)).1)
cera-7,14(27)-diene (5) ([a]D ϩ15.0°).1) Total synthesis of
Synthesis of (؉)-g-Polypodatetraene (2) from (؊)-Dri-
(Ϯ)-1 was reported based on mercury(II)trifluoromethane- menol (8) The elongation of the carbon chain from the
sulphonate–amine complex-induced olefin cyclization,3) primary alcohol group of the reported homodrimenol (22)4)
while total synthesis of (ϩ)-1 and (ϩ)-2 was not reported so derived from (Ϫ)-drimenol (8) was achieved stepwise by the
far. We previously reported that enantioselective acetylation following synthetic sequence. Bromination of 22 using CBr4
of (Ϯ)-albicanol (6) in the presence of isopropenyl acetate and Ph3P under neutral condition gave the corresponding
using lipase PL-266 from Alcaligenes sp. gave (ϩ)-albicanyl bromide 23, which was treated with NaCN in DMSO to
acetate (7) (Ͼ99% ee) and (Ϫ)-albicanol (6) (Ͼ99% ee). Re- provide the nitrile 24 in 78% overall yield. Dibal-H reduction
ductive deprotection of acetyl group in (ϩ)-7 afforded the of 24 yielded an aldehyde 25 (84%), which was reacted
natural (ϩ)-albicanol (6), which was treated with BF3·Et2O with (carbethoxyethylidene)triphenylphosphorane to give se-
to provide the natural (Ϫ)-drimenol (8).4) In this paper, we lectively (E)-26 in quantitative yield. Dibal-H reduction of
describe the first synthesis of the natural (ϩ)-a-polypodate- (E)-26 gave an allyl alcohol 27 in 89% yield, which was
traene (1) from (ϩ)-6 and (ϩ)-g-polypodatetraene (2) from subjected to bromination under neutral conditions (CBr4
(Ϫ)-8, and the determination of the absolute structure of and Ph3P) to afford the allyl bromide 28 in 73% yield. The
(ϩ)-2.
prepared 28 was immediately treated with sodium benzene
sulfinate to provide the sulfone 29 in 79% yield. The sulfone
29 was treated with LDA to provide the corresponding car-
Results and Discussion
a
Synthesis of (؉)- -Polypodatetraene (1) from (؉)-Albi- banion, which was treated with trans-geranyl bromide to fur-
canol (6) The method of elongation of the carbon chain nish the alkylated product 30 in 94% yield. Reductive elimi-
from the primary alcohol group of (ϩ)-6 was developed nation of 30 using [1,3-bis(diphenylphosphine)propane]-
stepwise by the following synthetic sequence. Mesylation of dichloropalladium (II) (PdCl2(dppp))5) gave the synthetic
(ϩ)-6 in pyridine gave the mesylate 9 (99%), which was (ϩ)-2 ([a]D ϩ6.9° (cϭ1.17, CHCl3)) in 59% yield, which
treated with NaCN in dimethyl sulfoxide (DMSO) to afford was consistent with the natural (ϩ)-2 ([a]D ϩ8.7° (cϭ0.9,
the nitrile compound 10 (49%) along with diexo-olefin 11 CHCl3)).1) This chiral synthesis of (ϩ)-2 indicates that the
(31%). Reduction of 10 with diisobutylaluminum hydride absolute configurations of the natural (ϩ)-2 are to be 5S, 9S,
(DIBAL) in toluene furnished the aldehyde 12 in 89% yield, 10S.
which was reduced with NaBH4 to provide the alcohol 13 in
quantitative yield. Bromination of 13 using carbon tetrabro- (1) and (ϩ)-g-polypodatetraene (2) was achieved from (ϩ)-
In conclusion, first synthesis of (ϩ)-a-polypodatetraene
To whom correspondence should be addressed. e-mail: akita @phar.toho-u.ac.jp
© 2002 Pharmaceutical Society of Japan

July 2002
931
Chart 1
Chart 2
recorded on JEOL AL 400 spectrometer in CDCl3. Carbon substitution de-
grees were established by distortionless enhancement by polarization trans-
fer (DEPT) pulse sequence. The fast atom bombardment mass spectra (FAB-
MS) were obtained with JEOL JMS 600H spectrometer. IR spectra were
recorded a JASCO FT/IR-300E spectrometer. Optical rotations were mea-
sured with a JASCO DIP-370 digital polarimeter. All evaporations were per-
formed under reduced pressure. For column chromatography, silica gel
albicanol (6) and (Ϫ)-drimenol (8), respectively. The ab-
solute structure of natural (ϩ)-2 was established to be
(5S,9S,10S)-polypoda-7,13(E),17(E),21-tetraene.
Experimental
All melting points were measured on a Yanaco MP-3S micro melting
point apparatus and are uncorrected. 1H- and 13C-NMR spectra were (Kieselgel 60) was employed.

932
Vol. 50, No. 7
NMR: d: 14.6 (q), 19.5 (t), 21.8 (q), 24.5 (t), 27.1 (t), 33.6 (s), 33.7 (q), 38.3
(t), 39.1 (t), 39.4 (s), 42.2 (t), 52.8 (d), 55.5 (d), 62.5 (t), 106.2 (t), 148.6 (s).
Anal. Calcd for C16H28O: C, 81.29; H, 11.94. Found: C, 81.02; H, 11.83%.
FAB-MS m/z: 237 (Mϩϩ1).
(1؅S,4a؅S,8a؅S)-(؉)-2-(1؅,2؅,3؅,4؅,4a؅,5؅,6؅,7؅,8؅,8a؅-Decahydro-
5؅,5؅,8a؅-trimethyl-2؅-methylene-1؅-naphtyl)-1-ethanol (13) 1) To
a
solution of (ϩ)-albicanol (6) (3.01 g, 13.5 mmol) and 4-dimethylaminopyri-
dine (DMAP) (0.161 g, 1.3 mmol) in pyridine (40 ml) was added MsCl
(1.93 g, 16.8 mmol) and the whole mixture was stirred for 2 h at room tem-
perature. The reaction mixture was diluted with saturated brine and extracted
with ether. The organic layer was washed with 2 M aqueous HCl, 7% aque-
ous NaHCO3 and dried over MgSO4. Evaporation of the organic solvent
gave a residue, which was chromatographed on silica gel (50 g, n-
hexane : AcOEtϭ20 : 1) to give a colorless oil 9 (4.06 g, 99%). 9: IR (neat):
1386, 1047 cmϪ1; [a]D30 ϩ27.5° (cϭ0.91, CHCl3); 1H-NMR: d: 0.74 (3H, s),
0.79 (3H, s), 0.86 (3H, s), 1.11 (1H, dd, Jϭ2.5, 12.5 Hz), 1.14—1.42 (4H,
m), 1.46—1.61 (2H, m), 1.66—1.75 (2H, m), 1.97—2.06 (1H, m), 2.10—
2.15 (1H, m), 2.40 (1H, ddd, Jϭ2, 4, 13 Hz), 2.96 (3H, s), 4.32 (1H, t,
Jϭ10 Hz), 4.47 (1H, dd, Jϭ4, 10 Hz), 4.59 (1H, br s), 4.89 (1H, br s). 13C-
NMR: d: 15.4 (q), 19.2 (t), 21.8 (q), 23.9 (t), 33.6 (s), 33.7 (q), 37.5 (t), 37.6
(q), 39.2 (t), 39.2 (s), 41.8 (t), 55.0 (d), 55.1 (d), 66.6 (t), 107.6 (t), 145.4 (s).
Anal. Calcd for C16H28O3S: C, 63.96; H, 9.39. Found: C,64.02; H, 9.41%.
2) A mixture of 9 (4.14 g, 13.8 mmol) and NaCN (3.41 g, 69.9 mmol) in
DMSO (60 ml) was stirred for 12 h at 100 °C. The reaction mixture was di-
luted with saturated brine and extracted with ether. The organic layer was
dried over MgSO4. Evaporation of the organic solvent gave a residue, which
was chromatographed on silica gel (60 g) to give a colorless oil 11 (0.889 g,
31%) from n-hexane eluate and a colorless oil 10 (1.573 g, 49%) from n-
hexane : AcOEtϭ20 : 1 eluate. A part of 10 was recrystallized from n-hexane
to give colorless plates. Compound 10: mp 91 °C; [a]D27 ϩ41.8° (cϭ0.89,
CHCl3); IR (KBr): 2240 cmϪ1 (CN); 1H-NMR: d: 0.69 (3H, s), 0.82 (3H, s),
0.90 (3H, s), 1.13 (1H, dd, Jϭ2.5, 12.5 Hz), 1.14—1.25 (2H, m), 1.33 (1H,
dq, Jϭ4, 12 Hz), 1.40—1.45 (1H, m), 1.50—1.62 (3H, m), 1.76 (1H, Jϭ2,
13 Hz), 2.08 (1H, dt, Jϭ5, 13 Hz), 2.17 (1H, dd, Jϭ4, 11 Hz), 2.33 (1H, dd,
Jϭ11, 17 Hz), 2.45 (1H, ddd, Jϭ2, 4, 13 Hz), 2.54 (1H, dd, Jϭ4, 17 Hz),
4.62 (1H, br s), 4.96 (1H, br s). 13C-NMR: d: 13.7 (q), 13.9 (t), 19.1 (t), 21.7
(q), 23.7 (t), 33.5 (q and s), 37.2 (t), 39.1 (t), 39.3 (s), 41.7 (t), 53.2 (d), 55.0
(d), 107.8 (s), 120.3 (s), 146.3 (t). Anal. Calcd for C16H25N: C, 83.06; H,
10.89; N, 6.05. Found: C, 83.38; H, 10.85; N, 5.95%. FAB-MS m/z: 232
(Mϩϩ1). Compound 11: IR (neat): 2928, 1632, 1460 cmϪ1; [a]D26 Ϫ186.6°
(cϭ0.42, CHCl3); 1H-NMR: d: 0.85 (3H, s), 0.86 (3H, s), 0.93 (3H, s), 1.11
(1H, dd, Jϭ3, 12.5 Hz), 1.18 (1H, dt, Jϭ4.5, 13.5 Hz), 1.38—1.57 (4H, m),
1.59—1.67 (2H, m), 1.75—1.78 (1H, m), 2.06—2.15 (1H, m), 2.45 (1H,
ddd, Jϭ2.5, 4.5, 13.5 Hz), 4.52 (1H, d, Jϭ2 Hz), 4.63 (1H, t, Jϭ2.5 Hz),
4.74 (1H, d, Jϭ2 Hz), 4.78 (1H, t, Jϭ2.5 Hz). 13C-NMR: d: 19.3 (t), 20.8 (q),
22.2 (q), 22.8 (t), 33.5 (q), 33.9 (s), 36.0 (t), 37.6 (t), 40.3 (s), 42.4 (t), 52.6
(d), 103.0 (t), 108.8 (t), 149.9 (s), 161.5 (s). Anal. Calcd for C15H24: C,
88.16; H, 11.84. Found: C, 87.92; H, 11.52%. FAB-MS m/z: 205 (Mϩϩ1).
3) To a solution of 10 (1.573 g, 6.8 mmol) in toluene (20 ml) was added
1 M DIBAL in toluene (8.1 ml, 8.1 mmol) at Ϫ78°C, the whole was stirred
for 30 min at the same temperature. After addition of acetone (5 ml), the re-
action mixture was diluted with 2 M aqueous HCl and extracted with ether.
The organic layer was washed with saturated brine and dried over MgSO4.
Evaporation of the organic solvent gave a residue, which was chro-
matographed on silica gel (30 g) to give a colorless oil 12 (1.433 g, 89%)
(1؅S,4a؅S,8a؅S)-(؉)-3-(1؅,2؅,3؅,4؅,4a؅,5؅,6؅,7؅,8؅,8a؅-Decahydro-
5؅,5؅,8a؅-trimethyl-2؅-methylene-1؅-naphtyl)propionaldehyde (16) 1)
To a solution of 13 (1.403 g, 5.9 mmol) in THF (30 ml) was added Ph3P
(5.463 g, 20.8 mmol) and CBr4 (5.345 g, 16.1 mmol) and the whole was
stirred for 15 min at room temperature. The reaction mixture was diluted
with saturated brine and extracted with ether. The organic layer was dried
over MgSO4. Evaporation of the organic solvent gave a residue, which was
chromatographed on silica gel (50 g, n-hexane) to give a colorless oil 14
(3.698 g). 14: 1H-NMR: d: 0.67 (3H, s), 0.78 (3H, s), 0.86 (3H, s), 1.05 (1H,
dt, Jϭ4, 12 Hz), 1.11 (1H, dd, Jϭ2.5, 12 Hz), 1.17 (1H, dt, Jϭ4, 12 Hz),
1.30 (1H, ddd, Jϭ4, 13, 20 Hz), 1.36—1.41 (1H, m), 1.45—1.62 (2H, m),
1.66—1.75 (2H, m), 1.78—1.82 (1H, m), 1.88—2.07 (3H, m), 2.38 (1H,
ddd, Jϭ2, 4, 13 Hz), 3.25 (1H, ddd, Jϭ7.5, 8, 8.5 Hz), 3.51 (1H, ddd, Jϭ4,
8, 8.5 Hz), 4.45 (1H, br s), 4.82 (1H, br s). 13C-NMR: d: 14.8 (q), 19.4 (t),
21.8 (q), 24.4 (t), 28.0 (t), 33.6 (s), 33.6 (q), 33.7 (t), 38.2 (t), 39.0 (t), 39.6
(s), 42.1 (t), 55.3 (d), 55.4 (d), 106.2 (t), 147.7 (s).
2) A mixture of 14 (3.698 g) and NaCN (4.53 g, 92.4 mmol) in DMSO
(30 ml) was stirred for 0.5 h at 100 °C. The reaction mixture was diluted
with saturated brine and extracted with ether. The organic layer was dried
over MgSO4. Evaporation of the organic solvent gave a residue, which was
chromatographed on silica gel (50 g, n-hexane : AcOEtϭ20 : 1) to give a col-
orless oil 15 (1.035 g, 71% overall yield from 13). Compound 15: IR (KBr):
2263 cmϪ1; [a]D27 ϩ37.5° (cϭ0.89, CHCl3); H-NMR: d: 0.66 (3H, s), 0.72
1
(3H, s), 0.86 (3H, s), 1.04—1.21 (3H, m), 1.25—1.41 (2H, m), 1.46—1.58
(2H, m), 1.65—1.75 (4H, m), 1.84—2.02 (2H, m), 2.24 (1H, dt, Jϭ7.5,
9 Hz), 2.38 (1H, ddd, Jϭ2.5, 4, 13 Hz), 2.44 (1H, ddd, Jϭ4, 8, 13 Hz), 4.39
(1H, br s), 4.85 (1H, br s). 13C-NMR: d: 14.6 (q), 16.3 (t), 19.4 (t), 20.4 (t),
21.8 (q), 24.5 (t), 33.6 (s), 33.6 (q), 38.1 (t), 39.0 (t), 39.8 (s), 42.0 (t), 55.3
(d), 55.8 (d), 106.2 (t), 120.2 (s), 147.1 (s). Anal. Calcd for C17H27N: C,
83.20; H, 11.09; N, 5.71. Found: C, 83.17; H, 11.30; N, 5.68%. FAB-MS
m/z: 244 (MϩϪ1), 245 (Mϩ).
3) To a solution of 15 (1.016 g, 4.1 mmol) in toluene (15 ml) was added
1 M DIBAL in toluene (10 ml, 10 mmol) at Ϫ78 °C, the whole was stirred for
15 min at the same temperature. The reaction mixture was worked up by the
same way as for the preparation of 12 to give a colorless oil 16 (0.842 g,
82%). Compound 16: IR (neat): 1726 cmϪ1; [a]D26 ϩ30.0° (cϭ0.66, CHCl3);
1H-NMR: d: 0.67 (3H, s), 0.78 (3H, s), 0.84 (3H, s), 1.01—1.08 (2H, m),
1.15 (1H, dt, Jϭ4, 13 Hz), 1.24—1.41 (2H, m), 1.44—1.61 (4H, m), 1.68—
1.79 (2H, m), 1.84—1.97 (2H, m), 2.23—2.38 (2H, m), 2.52—2.60 (1H, m),
4.40 (1H, br s), 4.81 (1H, br s), 9.73 (1H, t, Jϭ1.5 Hz). 13C-NMR: d: 14.4
(q), 16.0 (t), 19.5 (t), 21.8 (q), 24.5 (t), 33.6 (s), 33.7 (q), 38.3 (t), 39.1 (t),
39.9 (s), 42.2 (t), 43.3 (t), 55.5 (d), 56.3 (d), 106.4 (t), 147.8 (s), 202.5 (d).
Anal. Calcd for C17H28O: C, 82.20; H, 11.36. Found: C, 81.98; H, 11.18%.
FAB-MS m/z: 249 (Mϩϩ1).
(1؅S,2E,4a؅S,8a؅S)-(؉)-3-(1؅,2؅,3؅,4؅,4a؅,5؅,6؅,7؅,8؅,8a؅-Decahydro-
5؅,5؅,8a؅-trimethyl-2؅-methylene-1؅-naphtyl)-2-methyl-1-phenylsulfonyl-
2-pentene (20) 1) To a solution of 16 (0.826 g, 3.3 mmol) in benzene
(30 ml) was added Ph3PϭC(Me)COOEt (1.689 g, 4.6 mmol) and the whole
was refluxed for 12 h with stirring. The reaction mixture was evaporated to
give a residue, which was chromatographed on silica gel (50 g, n-
hexane : AcOEtϭ20 : 1) to give a colorless oil 17 (1.096 g, 99%). 17: IR
from n-hexane : AcOEtϭ20 : 1 eluate. Compound 12: IR (neat): 1725 cmϪ1
;
[a]D25 Ϫ18.1° (cϭ0.70, CHCl3); 1H-NMR: d: 0.71 (3H, s), 0.82 (3H, s), 0.90
(3H, s), 1.09 (1H, dt, Jϭ4.5, 13 Hz), 1.22 (1H, dd, Jϭ2.5, 12.5 Hz), 1.17—
1.24 (1H, m), 1.35 (1H, dq, Jϭ4, 12.5 Hz), 1.40—1.45 (1H, m), 1.47—1.53
(3H, m), 1.74 (1H, dq, Jϭ2.5, 13 Hz), 2.10 (1H, dt, Jϭ5, 12 Hz), 2.34—2.37
(1H, m), 2.42 (1H, ddd, Jϭ2.5, 4, 13 Hz), 2.43 (1H, ddd, Jϭ1.5, 4.5, 16 Hz),
2.49 (1H, ddd, Jϭ3, 10, 16 Hz), 9.64 (1H, dd, Jϭ1.5, 3 Hz). 13C-NMR: d:
14.6 (q), 19.2 (t), 21.7 (q), 23.9 (t), 33.5 (q and s), 37.5 (t), 38.9 (s), 39.4 (t),
39.8 (t), 42.0 (t), 51.0 (d), 55.3 (d), 108.0 (t), 148.5 (s), 203.5 (d). Anal.
Calcd for C16H26O: C, 81.98; H, 11.18. Found: C, 82.32; H, 11.28. FAB-MS
m/z: 235 (Mϩϩ1).
(neat): 1710 cmϪ1; [a]D27 ϩ40.7° (cϭ0.67, CHCl3); H-NMR: d: 0.64 (3H,
1
s), 0.77 (3H, s), 0.84 (3H, s), 0.99 (1H, dt, Jϭ4, 13 Hz), 1.06 (1H, dd, Jϭ3,
13 Hz), 1.15 (1H, dt, Jϭ4, 13 Hz), 1.22—1.63 (8H, m), 1.27 (3H, t,
Jϭ7 Hz), 1.68—1.73 (1H, m), 1.77 (3H, br s), 1.90—2.04 (2H, m), 2.22—
2.31 (1H, m), 2.34—2.40 (1H, m), 4.16 (2H, q, Jϭ7 Hz), 4.49 (1H, s), 4.82
(1H, s), 6.72 (1H, t, Jϭ8 Hz). 13C-NMR: d: 12.5 (q), 14.5 (q), 14.6 (q), 19.5
(t), 21.9 (q), 22.8 (t), 24.6 (t), 27.8 (t), 33.7 (s), 33.7 (q), 38.4 (t), 39.2 (t),
39.8 (s), 42.2 (t), 55.5 (d), 56.5 (d), 60.4 (t), 106.2 (t), 127.5 (s), 142.5 (d),
148.2 (s), 168.1 (s). Anal. Calcd for C22H36O2: C, 79.46; H, 10.91. Found: C,
79.51; H, 10.96%. FAB-MS m/z: 333 (Mϩϩ1).
4) To a solution of 12 (1.433 g, 6.1 mmol) in MeOH (30 ml) was added
NaBH4 (0.302 g, 8 mmol) at 0 °C, the whole was stirred for 30 min at the
same temperature. After addition of acetone (5 ml), the reaction mixture was
condensed to give a residue, which was diluted with saturated brine and ex-
tracted with ether. The organic layer was dried over MgSO4. Evaporation of
the organic solvent gave a residue, which was chromatographed on silica gel
(30 g, n-hexane : AcOEtϭ5 : 1) to afford a colorless oil 13 (1.432 g, 99%).
13: IR (neat): 3302 cmϪ1; [a]D24 ϩ27.6° (cϭ1.14, CHCl3); 1H-NMR: d: 0.65
(3H, s), 0.77 (3H, s), 0.84 (3H, s), 1.01 (1H, dt, Jϭ4, 13 Hz), 1.09 (1H, dd,
Jϭ3, 13 Hz), 1.15 (1H, dt, Jϭ4, 13 Hz), 1.24—1.39 (2H, m), 1.42—1.74
(8H, m), 1.96 (1H, dt, Jϭ5, 13 Hz), 2.35 (1H, ddd, Jϭ2.5, 4, 13 Hz), 3.44—
3.51 (1H, m), 3.65—3.71 (1H, m), 4.50 (1H, br s), 4.79 (1H, br s). 13C-
2) To a solution of 17 (1.076 g, 3.2 mmol) in toluene (20 ml) was added
1 M DIBAL in toluene (5 ml, 5 mmol) at Ϫ78 °C, the whole was stirred for
30 min at the same temperature. The reaction mixture was worked up by the
same way as for the preparation of 12 to give a colorless oil 18 (0.937 g,
99%). Compound 18: IR (neat): 3314 cmϪ1; [a]D27 ϩ6.8° (cϭ0.88, CHCl3);
1H-NMR: d: 0.65 (3H, s), 0.77 (3H, s), 0.85 (3H, s), 0.98 (1H, dt, Jϭ4,
13 Hz), 1.06 (1H, dd, Jϭ3, 12 Hz), 1.15 (1H, dt, Jϭ4, 13 Hz), 1.22—1.61
(8H, m), 1.61 (3H, br s), 1.68—1.74 (2H, m), 1.78—2.00 (2H, m), 2.09—
2.18 (1H, m), 2.37 (1H, ddd, Jϭ2, 3, 12 Hz), 3.98 (2H, br s), 4.51 (1H, br s),

July 2002
933
4.81 (1H, br s), 5.37 (1H, dt, Jϭ1, 7 Hz). 13C-NMR: d: 13.8 (q), 14.6 (q), (d), 123.2 (d), 133.4 (s). FAB-MS m/z: 299 (MϩϪ1), 297 (MϩϪ1).
19.5 (t), 21.9 (q), 23.6 (t), 24.6 (t), 26.7 (t), 33.7 (s), 33.7 (q), 38.5 (t), 39.2
(t), 39.7 (s), 42.3 (t), 55.6 (d), 56.4 (d), 69.1 (t), 106.1 (t), 126.8 (d), 134.5
2) A mixture of 23 (2.69 g) and NaCN (2.64 g, 53.9 mmol) in DMSO
(25 ml) was stirred for 0.5 h at 100 °C. The reaction mixture was worked up
(s), 148.5 (s). Anal. Calcd for C20H34O: C, 82.69; H, 11.80. Found: C, 82.77; by the same way as for the preparation of 15 to give a colorless oil 24
H, 11.91%. FAB-MS m/z: 291 (Mϩϩ1).
(1.004 g, 78% overall yield from 22). Compound 24: IR (neat): 2220 cmϪ1
;
1
3) To a solution of 18 (0.836 g, 2.88 mmol) and DMAP (0.176 g, [a]D24 Ϫ4.0° (cϭ0.8, CHCl3); H-NMR: d: 0.74 (3H, s), 0.83 (3H, s), 0.86
1.44 mmol) in CH2Cl2 (20 ml) was added TsCl (0.659 g, 3.45 mmol) at 0 °C
(3H, s), 1.04 (1H, dt, Jϭ4, 12.5 Hz), 1.16 (1H, dt, Jϭ4, 12.5 Hz), 1.19 (1H,
and the whole mixture was stirred for 7 h at room temperature. The reaction dd, Jϭ5, 12 Hz), 1.37—1.58 (4H, m), 1.65 (3H, br s), 1.73 (1H, br s), 1.79—
mixture was worked up by the same way as for the preparation of 14 to give 1.88 (3H, m), 1.93—2.02 (1H, m), 2.33 (1H, dt, Jϭ8.5, 17 Hz), 2.50 (1H,
a colorless oil 19 (0.382 g, 43%). Compound 19: [a]D24 ϩ25.3° (cϭ0.56, ddd, Jϭ5.5, 8.5, 17 Hz). 13C-NMR: d: 13.8 (q), 18.8 (t), 19.1 (t), 21.9 (q),
1
CHCl3); H-NMR: d: 0.64 (3H, s), 0.78 (3H, s), 0.84 (3H, s), 0.98 (1H, dt,
22.1 (q), 23.3 (t), 23.8 (t), 33.0 (s), 33.2 (q), 36.8 (s), 39.2 (t), 42.1 (t), 49.9
Jϭ4, 12.5 Hz), 1.06 (1H, dd, Jϭ3, 12.5 Hz), 1.15 (1H, dt, Jϭ4, 13 Hz), (d), 53.9 (d), 119.8 (s), 123.8 (d), 132.7 (s). FAB-MS m/z: 246 (Mϩϩ1).
1.24—1.60 (8H, m), 1.67 (3H, br s), 1.67—1.73 (1H, m), 1.80—1.99 (2H,
m), 2.09—2.18 (1H, m), 2.37 (1H, ddd, Jϭ2.5, 4.5, 13 Hz), 4.00 (2H, s),
4.40 (1H, br s), 4.81 (1H, br s), 5.49 (1H, t, Jϭ7 Hz).
3) To a solution of 24 (1.003 g, 4.1 mmol) in toluene (15 ml) was added
1 M DIBAL in toluene (11 ml, 11 mmol) at Ϫ78 °C, the whole was stirred for
1 h at the same temperature. The reaction mixture was worked up by the
4) To a solution of 19 (0.138 g, 0.44 mmol) in dimethylformamide (DMF) same way as for the preparation of 16 to give a colorless oil 25 (0.856 g,
(5 ml) was added PhSO2Na·2H2O (0.84 g, 6.2 mmol) at room temperature 84%). Compound 25: IR (neat): 1730 cmϪ1; [a]D24 Ϫ0.4° (cϭ1.11, CHCl3);
and the whole was stirred for 2 h at 60 °C. The reaction mixture was diluted 1H-NMR: d: 0.76 (3H, s), 0.82 (3H, s), 0.85 (3H, s), 0.92 (1H, dt, Jϭ4,
with saturated brine and extracted with ether. The organic layer was dried 13 Hz), 1.12 (1H, dt, Jϭ4, 13 Hz), 1.14 (1H, dd, Jϭ5, 12 Hz), 1.35—1.54
over MgSO4. Evaporation of the organic solvent gave a residue, which was (4H, m), 1.63 (3H, br s), 1.78—1.99 (4H, m), 2.37—2.45 (1H, m), 2.62 (1H,
chromatographed on silica gel (15 g, n-hexane : AcOEtϭ20 : 1) to afford a dddd, Jϭ1.5, 5, 10, 17 Hz), 5.40 (1H, br s), 9.72 (1H, t, Jϭ1.5 Hz). 13C-
colorless oil 20 (0.173 g, 93%). 20: IR (neat): 1386, 1307 cmϪ1; [a]D27 NMR: d: 13.7 (q), 18.9 (t), 19.2 (t), 22.0 (q), 22.3 (q), 23.9 (t), 33.0 (s), 33.3
ϩ25.2° (cϭ0.94, CHCl3); 1H-NMR: d: 0.61 (3H, s), 0.77 (3H, s), 0.84 (3H,
s), 0.91 (1H, dt, Jϭ4, 12.5 Hz), 1.02 (1H, dd, Jϭ3, 12.5 Hz), 1.11—1.17
(2H, m), 1.21—1.71 (11H, m), 1.68 (3H, s), 1.90—2.35 (2H, m), 3.70 (2H,
s), 4.36 (1H, br s), 4.77 (1H, br s), 5.02 (1H, t, Jϭ6.5 Hz), 7.51 (2H, t,
Jϭ1.5 Hz), 7.61 (1H, t, Jϭ1.5 Hz), 7.82 (2H, d, Jϭ1.5 Hz). 13C-NMR: d:
(q), 37.0 (s), 39.5 (t), 42.3 (t), 46.1 (t), 50.1 (d), 54.3 (d), 123.1 (d), 133.9
(s), 202.1 (d). FAB-MS m/z: 247 (MϩϪ1).
(1؅S,2E,4a؅S,8a؅S)-(؉)-5-(1؅,4؅,4a؅,5؅,6؅,7؅,8؅,8a؅-Octahydro-
2؅,5؅,5؅,8a؅-tetramethyl-1؅-naphtyl)-2-methyl-1-phenylsulfonyl-2-pen-
tene (29) 1) To a solution of 25 (0.856 g, 3.4 mmol) in benzene (20 ml)
14.6 (q), 16.8 (q), 19.5 (t), 21.8 (q), 23.1 (t), 24.5 (t), 27.5 (t), 33.7 (s), 33.7 was added Ph3PϭC(Me)COOEt (3.15 g, 9.7 mmol) and the whole was
(q), 38.4 (t), 39.2 (t), 39.7 (s), 42.2 (t), 55.5 (d), 56.3 (d), 66.3 (t), 106.0 (t), heated at 60 °C for 30 min with stirring. The reaction mixture was worked
122.9 (s), 128.4 (d), 128.4 (s), 128.7 (d), 133.3 (d), 136.9 (d), 148.3 (s).
Anal. Calcd for C26H38O2S: C, 75.31; H, 9.24. Found: C, 75.02; H, 9.01%..
FAB-MS m/z: 415 (Mϩϩ1).
up by the same way as for the preparation of 17 to give a colorless oil 26
(1.135 g, 99%). 26: IR (neat): 1711 cmϪ1; [a]D25 ϩ13.5° (cϭ0.79, CHCl3);
1H-NMR: d: 0.73 (3H, s), 0.84 (3H, s), 0.86 (3H, s), 0.94 (1H, dt, Jϭ4,
(؉)-a-Polypodatetraene (1) 1) n-Butyllithium (1.6 M n-BuLi in 13 Hz), 1.14 (1H, dt, Jϭ4, 13 Hz), 1.16 (1H, dd, Jϭ5, 12 Hz), 1.23—1.34
hexane, 0.5 ml, 0.8 mmol) was added to a stirred solution of diisopropyl- (1H, m), 1.27 (3H, t, Jϭ7 Hz), 1.36—1.48 (3H, m), 1.49—1.59 (2H, m),
amine (0.077 g, 0.76 mmol) in tetrahydrofuran (THF) (2 ml) at Ϫ78 °C under 1.62 (1H, br s), 1.69 (3H, br s), 1.82 (3H, br s), 1.79—1.88 (2H, m), 1.91—
an argon atmosphere and the mixture was stirred for 15 min at the same tem-
perature. A solution of 20 (0.154 g, 0.37 mmol) in THF (2 ml) was added to
the resulting LDA-THF solution and the whole mixture was stirred for (q), 14.4 (q), 18.9 (t), 22.0 (q), 22.3 (q), 23.9 (t), 26.2 (t), 31.0 (t), 33.1 (s),
15 min at the same temperature. To the above reaction mixture was added a 33.3 (q), 36.9 (s), 39.3 (t), 42.3 (t), 50.2 (d), 54.5 (d), 60.4 (t), 122.5 (d),
1.99 (1H, m), 2.07—2.17 (1H, m), 2.29—2.38 (1H, m), 4.17 (2H, q,
Jϭ7 Hz), 5.38 (1H, br s), 6.74 (1H, t, Jϭ8 Hz). 13C-NMR: d: 12.6 (q), 13.6
solution of trans-geranyl bromide (0.167 g, 0.77 mmol) in THF (2 ml) and
127.5 (s), 134.6 (s), 142.1 (d), 168.0 (s). Anal. Calcd for C22H36O2: C, 79.46;
the whole mixture was stirred for 15 min at Ϫ78 °C, for 1 h at Ϫ20 °C and H, 10.91. Found: C, 79.10; H, 10.93%. FAB-MS m/z: 333 (Mϩϩ1).
for 1 h at room temperature. The reaction mixture was diluted with saturated
brine and extracted with Et2O. The organic layer was dried over MgSO4. Re-
2) To a solution of 26 (1.151 g, 3.5 mmol) in toluene (15 ml) was added
1 M DIBAL in toluene (9 ml, 9 mmol) at Ϫ78 °C, the whole was stirred for
moval of the organic solvent gave an oily product, which was chro- 30 min at the same temperature. The reaction mixture was worked up by the
matographed on silica gel (15 g, n-hexane : AcOEtϭ20 : 1) to afford 21 as a same way as for the preparation of 18 to give a colorless oil 27 (0.894 g,
homogeneous oil (0.115 g, 56%). FAB-MS m/z: 551 (Mϩϩ1).
89%). Compound 27: IR (neat): 3332 cmϪ1; [a]D22 ϩ3.2° (cϭ0.81, CHCl3);
2) A mixture of 21 (0.115 g, 0.21 mmol) and 5% Na–Hg (1.32 g, 1H-NMR: d: 0.74 (3H, s), 0.85 (3H, s), 0.87 (3H, s), 0.95 (1H, dt, Jϭ4,
0.3 mmol) in MeOH (20 ml) was refluxed for 12 h with stirring. The reaction 9 Hz), 1.15 (1H, dt, Jϭ4, 9 Hz), 1.17 (1H, dd, Jϭ5, 12 Hz), 1.20—1.28 (1H,
mixture was evaporated to give a residue, which was diluted with saturated m), 1.30 (1H, br s), 1.38—1.56 (4H, m), 1.63 (1H, br s), 1.68 (3H, br s), 1.71
brine and extracted with ether. The organic layer was dried over MgSO4. (3H, br s), 1.80—1.90 (2H, m), 1.93—2.05 (2H, m), 2.18—2.27 (1H, m),
Evaporation of the organic solvent gave a residue, which was chro- 4.00 (2H, br s), 5.39 (1H, br s), 5.42 (1H, t, Jϭ7 Hz). 13C-NMR: d: 14.0 (q),
matographed on silica gel (15 g, n-hexane) to give a colorless oil (ϩ)-1
14.3 (q), 19.3 (t), 22.3 (q), 22.6 (q), 24.3 (t), 27.4 (t), 30.4 (t), 33.4 (s), 33.6
(t), 37.2 (s), 39.6 (t), 42.7 (t), 50.5 (d), 54.8 (d), 69.3 (t), 122.5 (d), 126.8 (d),
(0.036 g, 42%) as a colorless oi. Compound (ϩ)-1: IR (neat): 3076,
1
1655 cmϪ1; [a]D26 ϩ29.6° (cϭ0.22, CHCl3); H-NMR: d: 0.64 (3H, s), 0.77 134.8 (s), 135.4 (s). Anal. Calcd for C20H34O: C, 82.69; H, 11.80. Found: C,
(3H, s), 0.85 (3H, s), 0.98 (1H, dt, Jϭ4, 12.5 Hz), 1.06 (1H, dd, Jϭ2.5, 82.43; H, 11.80%. FAB-MS m/z: 291 (Mϩϩ1).
12.5 Hz), 1.15 (1H, dt, Jϭ4, 13 Hz), 1.23—1.84 (17H, m), 1.54 (3H, br s),
3) To a solution of 27 (0.681 g, 2.3 mmol) in THF (20 ml) was added Ph3P
1.57 (6H, br s), 1.65 (3H, br s), 1.92—2.09 (2H, m), 2.33—2.49 (2H, m),
(1.34 g, 5.1 mmol) and CBr4 (1.64 g, 4.9 mmol) and the whole was stirred for
4.51 (1H, br s), 4.80 (1H, br s), 5.05—5.12 (3H, m). 13C-NMR (BCM): d: 1 h at room temperature. The reaction mixture was worked up by the same
14.5, 16.0, 16.0, 17.8, 19.6, 21.9, 23.8, 24.6, 25.7, 26.8, 26.8, 29.7, 33.6, way as for the preparation of 23 to give a colorless oil 28 (0.606 g, 73%).
33.6, 38.5, 39.1, 39.6, 39.8, 39.8, 42.3, 55.6, 56.2, 106.1, 124.2, 124.4,
125.1, 131.1, 134.8, 134.8, 148.4. Anal. Calcd for C30H50: C, 87.73; H,
12.27. Found: C, 87.77; H, 12.01%. EI-MS m/z: 409 (MϩϪ1), 411 (Mϩϩ1).
Compound 28: IR (neat): 2929 cmϪ1; [a]D22 ϩ3.2° (cϭ0.81, CHCl3); 1H-
NMR: d: 0.72 (3H, s), 0.84 (3H, s), 0.86 (3H, s), 0.94 (1H, dt, Jϭ4, 13 Hz),
1.10—1.27 (3H, m), 1.36—2.04 (9H, m), 1.68 (3H, br s), 1.75 (3H, br s),
(1؅S,4a؅S,8a؅S)-(؉)-3-(1؅,4؅,4a؅,5؅,6؅,7؅,8؅,8a؅-Octahydro-2؅,5؅,5؅,8a؅- 2.15—2.25 (1H, m), 3.96 (2H, s), 5.38 (1H, br s), 5.59 (1H, t, Jϭ7 Hz). 13C-
tetramethyl-1؅-naphtyl)propionaldehyde (25) 1) To a solution of 22 NMR: d: 13.6 (q), 14.9 (q), 18.9 (t), 22.0 (q), 22.3 (q), 23.9 (t), 26.6 (t), 30.6
(1.234 g, 5.2 mmol) in THF (20 ml) was added Ph3P (2.74 g, 10.4 mmol) and (t), 33.1 (s), 33.3 (q), 36.8 (s), 39.3 (t), 42.0 (t), 42.4 (t), 50.2 (d), 54.2 (d),
CBr4 (3.45 g, 10.4 mmol) and the whole was stirred for 30 min at room tem- 122.3 (d), 131.6 (d), 131.6 (s), 134.9 (s).
perature. The reaction mixture was worked up by the same way as for the
4) To a solution of 28 (0.578 g, 1.6 mmol) in DMF (20 ml) was added
preparation of 14 to give a colorless oil 23 (2.69 g). 23: IR (neat): PhSO2Na·2H2O (0.813 g, 4.1 mmol) at room temperature and the whole was
2927 cmϪ1; [a]D25 ϩ9.9° (cϭ0.78, CHCl3); NMR: d: 0.74 (3H, s), 0.86 (3H,
s), 0.87 (3H, s), 1.01 (1H, dt, Jϭ4, 13 Hz), 1.15 (1H, dt, Jϭ4, 13 Hz), 1.18
stirred for 30 min at 60 °C. The reaction mixture was worked up by the same
way as for the preparation of 20 to give a colorless oil 29 (0.539 g, 79%).
(1H, dd, Jϭ5, 12 Hz), 1.37—1.58 (4H, m), 1.66 (3H, br s), 1.70—1.89 (4H, Compound 29: IR (neat): 1310, 1141 cmϪ1; [a]D23 ϩ13.7° (cϭ1.51, CHCl3);
m), 1.93—2.04 (2H, m), 3.34 (1H, q, Jϭ8.5 Hz), 3.56 (1H, dt, Jϭ4, 8.5 Hz), 1H-NMR: d: 0.70 (3H, s), 0.85 (3H, s), 0.87 (3H, s), 0.82—0.91 (1H, m),
5.42 (1H, br s). 13C-NMR: d: 13.8 (q), 18.8 (t), 22.0 (q), 22.2 (q), 23.9 (t),
0.94—1.20 (1H, m), 1.10—1.18 (1H, m), 1.13 (1H, dd, Jϭ5, 12 Hz), 1.20—
31.4 (t), 33.1 (s), 33.2 (q), 34.5 (t), 36.7 (s), 39.3 (t), 42.3 (t), 50.1 (d), 54.0 1.27 (1H, m), 1.37—1.54 (4H, m), 1.62 (3H, br s),1.69—1.75 (1H, m), 1.75

934
Vol. 50, No. 7
(3H, br s), 1.82—1.98 (3H, m), 2.15—2.30 (1H, m), 3.73 (2H, s), 5.04 (1H, oration of the organic solvent gave a residue, which was chromatographed
t, Jϭ7 Hz), 5.37 (1H, br s), 7.52 (2H, t, Jϭ8 Hz), 7.62 (1H, t, Jϭ8 Hz), 7.84
(2H, d, Jϭ8 Hz). 13C-NMR: d: 13.4 (q), 16.6 (q), 18.7 (t), 21.8 (q), 22.0 (q),
on silica gel (15 g, n-hexane) to give a colorless oil (ϩ)-2 (0.021 g, 59%) as
a colorless oil. Compound (ϩ)-2: IR (neat): 2921, 1448 cmϪ1; [a]D24 ϩ6.9°
23.7 (t), 26.3 (t), 30.5 (t), 32.9 (s), 33.1 (q), 36.6 (s), 39.1 (t), 42.2 (t), 49.4 (cϭ1.17, CHCl3); 1H-NMR: d: 0.72 (3H, s), 0.83 (3H, s), 0.85 (3H, s), 0.94
(d), 54.2 (d), 66.1 (t), 122.2 (d), 122.8 (s), 128.2 (d), 128.5 (d), 133.1 (d), (1H, dt, Jϭ4, 13 Hz), 1.09—1.23 (3H, m), 1.31—1.70 (9H, m), 1.57 (6H, s),
134.5 (s), 136.3 (d), 138.0 (s). Anal. Calcd for C16H28O: C, 81.29; H,
11.94%. Found: C, 81.27; H, 12.04%. FAB-MS m/z: 415 (Mϩϩ1).
(؉)-g-Polypodatetraene (2) 1) n-Butyllithium (1.6 M n-BuLi in hexane,
1.59 (3H, s), 1.66 (3H, s), 1.79—1.88 (2H, m), 1.90—2.20 (10H, m), 2.67
(1H, t, Jϭ7 Hz), 5.06—5.14 (2H, m), 5.36 (1H, br s). 13C-NMR (BCM): d:
13.6, 16.1, 16.3, 17.8, 19.0, 21.9, 22.3, 23.9, 25.8, 26.7, 26.9, 27.4, 30.3,
0.95 ml, 1.5 mmol) was added to a stirred solution of diisopropylamine 33.0, 33.3, 36.8, 39.3, 39.8, 39.8, 42.4, 50.2, 54.3, 121.9, 124.1, 124.3,
(0.094 g, 0.9 mmol) in THF (3 ml) at Ϫ78 °C under an argon atmosphere and 124.7, 131.1, 134.8, 134.8, 135.5. Anal. Calcd for C30H50: C, 87.73; H,
the mixture was stirred for 15 min at the same temperature. A solution of 29 12.27. Found: C, 87.89; H, 12.35%. FAB-MS m/z: 409 (MϩϪ1).
(0.193 g, 0.5 mmol) in THF (1 ml) was added to the resulting LDA-THF so-
lution and the whole mixture was stirred for 15 min at the same temperature. References
To the above reaction mixture was added a solution of trans-geranyl bromide
(0.203 g, 0.9 mmol) in THF (1 ml) and the whole mixture was stirred for
30 min at Ϫ78 °C and for 2 h at Ϫ20 °C. The reaction mixture was worked
up by the same way as for the preparation of 21 to give a colorless oil 30
(0.241 g, 94%).
2) To a solution of 30 (0.048 g, 0.1 mmol) and PdCl2 (dppp) (20.6 mg,
0.05 mmol) in THF was added 1 M LiHBEt3 in THF (0.54 ml, 0.54 mmol)
and the whole mixture was stirred for 2 h at room temperature. The reaction
mixture was diluted with 2 M aqueous NaOH and extracted with ether. The
organic layer was washed with saturated brine and dried over MgSO4. Evap-
1) Shiojima K., Arai Y., Masuda K., Kamada T., Ageta H., Tetrahedron
Lett., 24, 5733—5736 (1983).
2) Imamura P. M., Pantarotto H., Liebigs Ann., 1995, 1891—1894
(1995).
3) Nishizawa M., Nishide H., Hayashi Y., J. Chem. Soc., Chem.
Commun., 1984, 467—468 (1984).
4) Akita H., Nozawa M., Mitsuda A., Ohsawa H., Tetrahedron: Asymme-
try, 11, 1375—1388 (2000).
5) Mohri M., Kinoshita H., Inomata K., Kotake H., Chem. Lett., 1985,
451—454 (1985).