Total synthesis of a monocyclofarnesane dinorsesquiterpenoid isolated from mushroom ingested by beetle: Selectivity in solid-state Baeyer-Villiger reaction

Article abstract of DOI:10.1039/b003571h

Dinorsesquiterpenoid 1 is synthesised starting from (S)-(+)-Wieland-Miescher ketone analogue 5 via solid-state Baeyer-Villiger reaction as a key step. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b003571h

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Total synthesis of a monocyclofarnesane dinorsesquiterpenoid
isolated from mushroom ingested by beetle: Selectivity in solid-
state Baeyer–Villiger reaction
1
Hisahiro Hagiwara,*a Hidenori Nagatomo,a Fumiko Yoshii,a Takashi Hoshi,a Toshio Suzukia
and Masayoshi Andob
a Graduate School of Science and Technology, Niigata University, 8050, 2-nocho, Ikarashi,
Niigata 950-2181, Japan
b Faculty of Engineering, Niigata University, 8050, 2-nocho, Ikarashi, Niigata 950-2181, Japan
Received (in Cambridge, UK) 4th May 2000, Accepted 4th July 2000
Published on the Web 31st July 2000
Dinorsesquiterpenoid 1 is synthesised starting from (S)-(ϩ)-Wieland–Miescher ketone analogue 5 via solid-state
Baeyer–Villiger reaction as a key step.
Dinorsesquiterpenoid 1 was isolated by Hashimoto and
Asakawa1 along with norsesquiterpenoid 3 from the dry,
powdery, inedible mushroom Cryptoporus volvatus, bio-
transformed by the beetle Tibolium castaneum, and might be
one of the metabolites of cryptoporic acid 4 which has strong
inhibitory activity against the release of superoxide anion rad-
ical from guinea pig peritoneal macrophages. The structure of
compound 1 was determined as the methyl ester 2 because of
the instability of 1 and the absolute stereostructure at C-2 was
established to be R as depicted in Fig. 1 by applying Kusumi’s
PGME method (phenylglycine methyl ester).2 Our continuing
interest in total syntheses of monocyclofarnesane terpenoids
delineates herein the first total synthesis of the dinorsesquiter-
penoid 2 subsequent to our previous synthesis of 3.3
requisite stereocentres (Scheme 1). Reduction of α,β-
unsaturated moiety of the enone 6 with lithium in liquid
ammonia provided, in 84% yield, the ketone 7, which was
reduced with lithium aluminium hydride to give a mixture of
two inseparable isomeric alcohols 8 and 9. Deprotection of the
ketal provided β-alcohol 10 and α-alcohol 11 in 83 and 12%
yield, respectively in two steps. Coupling constants of the pro-
ton at C-5 of 10 (δ 2.64, ddq, J 14.0, 13.8 and 7.0 Hz) revealed
the equatorial orientation of the methyl group at C-5 and the
trans ring junction of the decalin framework. Protection of
β-alcohol 10 with chlorotrimethylsilane (TMSCl) provided
TMS ether 12 in 94% yield.
Monomethylation at C-2 of 12 and its derivatives was not
trivial, as anticipated from literature precedents.3,5 Attempts to
introduce a methoxycarbonyl or formyl group to activate C-2
have failed. Reaction with potassium hydride as a base gave an
inseparable mixture of mono- and di-methylated products
along with O-methylated product. Several initial attempts using
lithium diisopropylamide (LDA) and iodomethane (MeI)
led only to recovered ketone 12. Addition of hexamethyl-
phosphoric triamide (HMPA) increased the amount of
dimethylated product. After several investigations, we finally
found that treatment of the ketone 12 with LDA at Ϫ20 ЊC
followed by addition of MeI provided an inseparable 1:1
diastereomeric mixture of monomethylated products 13 and 14
in 73% yield. When the hydroxy group at C-6 was protected as
its tert-butyldimethylsilyl (TBDMS) ether, all similar attempts
have failed.
Results and discussion
According to the plausible biogenetic pathway1 of 3 via bio-
Baeyer–Villiger reaction, synthesis has started from the known
enone
6 derived from optically active (S)-(ϩ)-Wieland–
Miescher ketone analogue 54 [>95% enantiomeric excess (ee)]
targeting 1-decalones 14 or 16 as a key intermediate with all
The mixture of 13 and 14, upon treatment with sodium
methoxide, equilibrated in 98% yield with concomitant depro-
tection of the TMS group to afford thermodynamically stable
α-isomer 15 in which orientation of the methyl group was
apparent from coupling patterns of the proton at C-2 (δ 2.75,
d × quint, J 12.8 and 6.4 Hz). All the requisite stereocentres of
the target compound 1 were furnished at this stage.
Baeyer–Villiger reaction of 15 and its derivatives was not
easy. Reaction of the ketone 15 in solvent with excess of tri-
fluoroacetic acid (TFA), m-chloroperbenzoic acid (MCPBA) or
monoperphthalic acid magnesium salt (MMPA) resulted in
recovery of starting material 15 with partial decomposition.
Solid-state reaction of 15 with MCPBA or MMPA gave a small
amount of lactonic compounds. TMS ether 14 gave a similar
result. Then, the hydroxy group of 15 was quantitatively pro-
tected as its acetate to provide 16. Though conventional
Fig. 1
DOI: 10.1039/b003571h
J. Chem. Soc., Perkin Trans. 1, 2000, 2645–2648
This journal is © The Royal Society of Chemistry 2000
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Table 1 Solid-state Baeyer–Villiger oxidation of the decalones 14–16,
22 and 24
Reaction
conditions
Product
Yield (%)
Entry
Decalone
Reagent
1
2
3
4
14
15
15
16
MCPBA
MMPAb
MCPBA
MCPBA
rt, 144 h
50 ЊC, 7 h
rt, 112 h
rt, 72 h
26 0 (73)a
26 22 (54)a
26 15 (52)a
17 58
18 27
5
6
22
24
MCPBA
MCPBA
rt, 16 h
rt, 16 h
23 90
25 84c
a The decalone 15 was recovered. b Monoperoxyphthalic acid mag-
nesium salt. c See ref. 3.
Fig. 2
hydroxy ester 20 and acetoxy ester 21 in 82% combined yield
(62:38 ratio). Jones oxidation of the hydroxy ester afforded
the ester 2 in 79% yield. Spectral data of synthetic 2 were
completely identical with the data of natural 2 including optical
rotation [α]D23 Ϫ13.1 (c 0.26, CHCl3) {lit.,1 [α]D23 Ϫ14.3 (c 0.28,
CHCl3)}.†
Some of our results in the solid-state Baeyer–Villiger reac-
tions are compiled in Table 1. Smooth reactions and complete
regioselectivities with the decalones 22 and 24 in entries 5 and 6
rather than with the decalone 16 in entry 4 might be the result
of 1,3-steric repulsion between two axial methyl groups at C-5
and C-8a in 22 and 24 (Fig. 2). The rate-determining step of
Baeyer–Villiger reaction is migration from Crieege’s intermedi-
ate via an early transition state.9,10
Scheme 1 Reagents, conditions and yields: i, Li/liq. NH3, THF, H2O,
84%; ii, LAH, Et2O; iii, PTSA, aq. acetone, 95% from 7; iv, TMSCl,
Et3N, CH2Cl2, 94%; v, LDA, THF, MeI, 73%; vi, NaOMe, HOMe,
98%; vii, Ac2O, DMAP, pyridine, quant.; viii, MCPBA, solid state,
85%; ix, aq. NaOH, quant. (17 → 19, 21 → 19); x, K2CO3, aq.
MeOH, 82% (20:21 = 62:38); xi, CH2N2, Et2O, quant.; xii, Jones
reagent, 79% (20 → 2) (17 → 19 → 1 → 2 52% overall in 3
steps).
To this end, semiempirical
molecular orbital calculations, PM3,11 on Crieege’s intermedi-
ates 27a and 27b derived from the decalone 24 were performed
by using Gaussian 98, Revision A.6,12 with Silicon Graphics
Onyxs. Though the difference in heat of formation between
intermediates 27a and 27b was little (0.07 kcal‡), the C-1–C-8a
bond in the more stable intermediate 27a was longer (1.61 Å)13
than the C-1–C-2 bond (1.56 Å) and was antiperiplanar
(dihedral angle 173Њ) to the O–O bond. These results explain
the regioselectivity of the present Baeyer–Villiger reactions.
Substrates 14–16, 22 and 24 in Table 1 were all unreactive
in Baeyer–Villiger reactions in a solvent. However, an exact
explanation of solid-state Baeyer–Villiger reactions is yet to be
published.
Baeyer–Villiger oxidation of 16 in a solvent with MCPBA or
7
trifluoroperacetic acid6 with or without Yb(OTf)3 was very
sluggish and resulted again in recovery of 16, solid-state reac-
tion8 of the acetate 16 with MCPBA furnished desired lactonic
compound 17 and its regioisomer 18 in 58 and 27% yield,
respectively.
Hydrolysis of the lactone 17 with aq. sodium hydroxide fol-
lowed by Jones oxidation provided very unstable acid 1, which
was soon esterified with diazomethane to give methyl ester 2
in 52% overall yield in three steps. Alternatively, an attempt
of selective hydrolysis of the keto ester 17 provided a mixture of
† [α]D-Values are given in units of 10Ϫ1 deg cm2 gϪ1
‡ 1 cal = 4.184 J.
.
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J. Chem. Soc., Perkin Trans. 1, 2000, 2645–2648

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In conclusion, we have completed the total synthesis of
dinorsesquiterpenoid 1, demonstrating the utility of solid-state
Baeyer–Villiger oxidation in natural-product synthesis.
(1H, ddq, J 14.0, 13.8, 7.0) and 3.10 (1H, m) (Found: C, 73.05;
H, 10.0. Calc. for C12H20O2: C, 73.4; H, 10.3%).
Compound 11 had mp 72–73 ЊC; νmax/cmϪ1 3634, 3514, 2868,
1709, 1448, 1373, 1311, 1263, 1165, 1101, 1038 and 964; δH(200
MHz) 0.99 (3H, d, J 6.3), 1.12 (3H, s), 1.19–2.30 (12H, m), 2.64
(1H, ddd, J 14.0, 13.8 and 6.8) and 3.86 (1H, m).
Experimental
Mps were determined with a Yanaco MP hot-stage apparatus
and are uncorrected. IR spectra were recorded on a Shimadzu
FT/IR-4200 spectrophotometer for solutions in tetrachloro-
methane. 1H NMR spectra were obtained for solutions in
deuteriochloroform with Varian Gemini 200H (200 MHz) and
Unity 500plus (500 MHz) instruments with tetramethylsilane as
internal standard. J-Values are in Hz. The 13C NMR spectrum
for ester 2 was run on a Varian unity 500plus (125 MHz)
instrument with chloroform as internal standard. Mass spec-
tral data were obtained with a JEOL GC-Mate spectrometer.
Specific rotations were measured with a Horiba SEPA-200
spectrophotometer for solutions in chloroform. Medium-
pressure liquid chromatography (MPLC) was carried out on
a JASCO PRC-50 instrument with a silica gel-packed column.
Microanalyses were carried out in the Instrumental Analysis
Center for Chemistry, Tohoku University.
(4aS,5S,6S,8aS)-(؊)-3,4,4a,5,6,7,8,8a-Octahydro-5,8a-
dimethyl-6-(trimethylsiloxy)naphthalen-1(2H)-one 12
A solution of the alcohol 10 (1.38 g, 7.04 mmol), chloro-
trimethylsilane (1.10 cm3, 8.69 mmol) and triethylamine (2.0
cm3, 14.3 mmol) in dichloromethane (20 cm3) was stirred at
room temperature for 20 min under nitrogen atmosphere. The
reaction was quenched by addition of aq. sodium hydrogen
carbonate and extracted with ethyl acetate (×2). The organic
layer was washed with brine and dried over anhydrous Na2SO4.
Column chromatography (ethyl acetate–n-hexane 1:5) gave
12 (1.78 g, 94%) as a colourless oil; [α]D20 Ϫ26.1 (c 0.56, CHCl3);
νmax/cmϪ1 2955, 1709, 1449, 1371, 1252, 1103, 1096 and 1028;
δH(200 MHz) 0.12 (9H, s), 0.95 (3H, d, J 6.3), 1.14 (3H, s),
1.15–1.90 (9H, m), 2.01–2.26 (2H, m), 2.63 (1H, ddd, J 13.8,
13.6 and 7.0) and 3.05 (1H, ddd, J 10.8, 9.8 and 5.1) (Found: C,
67.1; H, 10.3. Calc. for C15H28O2Si: C, 67.1; H, 10.5%).
(4aS,5S,8aS)-(؊)-3,4,4a,5,8,8a-Hexahydro-5,8a-dimethyl-
naphthalene-1(2H),6(7H)-dione 1-ethylene ketal 7
(2S,4aS,5S,6S,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-2,5,8a-
trimethyl-6-(trimethylsiloxy)naphthalen-1(2H)-one 13 and
(2R,4aS,5S,6S,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,8a-
trimethyl-6-(trimethylsiloxy)naphthalen-1(2H)-one 14
To a solution of lithium (445 mg, 64 mml) in distilled liquid
ammonia (100 cm3) was added a solution of the enone 6 (3.03 g,
12.8 mmol) in THF (50 cm3) at Ϫ78 ЊC under nitrogen atmos-
phere. After being refluxed for 30 min, water (0.23 cm3, 12.8
mmol) was added at Ϫ78 ЊC. After being refluxed for 40 min,
the reaction was quenched by cautious addition of water (0.495
cm3, 24 mmol) and ammonium chloride (3 g). After evapor-
ation of liquid ammonia, the organic layer was extracted with
ethyl acetate (×2) and the combined extract was washed with
brine and dried over anhydrous Na2SO4. Evaporation of the
solvent in vacuo followed by column chromatography of the
residue on silica gel (ethyl acetate–n-hexane 1:5) gave 7 (2.58 g,
84%) as a colourless oil, [α]D23 Ϫ8.7 (c 1.22, CHCl3); νmax/cmϪ1
2955, 1713, 1186, 1088 and 1042; δH(200 MHz) 0.99 (3H, d,
J 6.6), 1.24 (3H, s), 1.32–2.04 (9H, m), 2.15–2.53 (3H, m)
and 3.82–4.05 (4H, m) (Found: C, 70.29; H, 9.48. Calc. for
C14H22O3: C, 70.55; H, 9.3%).
To a stirred solution of diisopropylamine (0.76 cm3, 5.8 mmol)
in THF (15 cm3) was added an n-hexane solution (1.57 M) of
n-butyllithium (3.7 cm3, 5.8 mmol) at 0 ЊC under nitrogen
atmosphere. After being stirred for 20 min the mixture was
treated with a solution of decalone 12 (750 mg, 2.91 mmol) in
THF (15 cm3) at Ϫ78 ЊC and the solution was stirred at Ϫ20 ЊC
for 20 min. MeI (0.50 cm3, 8.03 mmol) was added at Ϫ78 ЊC
and the reaction temperature was raised gradually from Ϫ78 to
0 ЊC over a period of 5 h. The reaction was quenched by addi-
tion of aq. ammonium chloride and extracted with ethyl acetate
(×2). The organic layer was washed with brine and dried over
anhydrous Na2SO4. MPLC purification (ethyl acetate–n-hexane
1:5) gave a diastereomeric mixture of decalones 13 and 14 (595
mg, 73%, ratio 1:1) as an oil along with recovered starting
decalone 12 (53 mg, 7% recovery).
Compound 13 had νmax/cmϪ1 2965, 1709, 1454, 1261, 1217,
1126, 1076 and 1036; δH(200 MHz) 0.12 (9H, s), 0.92 (3H, d,
J 6.4), 0.98 (3H, d, J 6.4), 1.14 (3H, s), 1.16–1.96 (9H, m),
2.09 (1H, m), 2.74 (1H, dqd, J 12.8, 6.4 and 6.4) and 3.05
(1H, m).
(4aS,5S,6S,8aS)-(؊)-3,4,4a,5,6,7,8,8a-Octahydro-6-hydroxy-
5,8a-dimethylnaphthalen-1(2H)-one 10 and (4aS,5S,6R,8aS)-
3,4,4a,5,6,7,8,8a-octahydro-6-hydroxy-5,8a-dimethyl-
naphthalen-1(2H)-one 11
To a stirred solution of the ketone 7 (1.06 g, 4.44 mmol) in
anhydrous diethyl ether (13 cm3) was added lithium aluminium
hydride (82 mg, 2.28 mmol) at Ϫ78 ЊC under nitrogen atmos-
phere. After being stirred for 1 h, the reaction mixture was
quenched by cautious addition of aq. ammonium chloride. Fil-
tration through anhydrous Na2SO4 followed by evaporation of
diethyl ether provided an inseparable mixture of (4aS,5S,
6S,8aS)- and (4aS,5S,6R,8aS)-3,4,4a,5,6,7,8,8a-octahydro-6-
hydroxy-5,8a-dimethylnaphthalen-1(2H)-one ethylene ketal 8
and 9 (1.00 g).
Compound 14 had νmax/cmϪ1 2973, 1702, 1455, 1378, 1035
and 993; δH(200 MHz) 0.12 (9H, s), 0.94 (3H, d, J 5.9), 1.04
(3H, d, J 6.6), 1.05 (3H, s), 1.10–2.10 (10H, m), 2.49 (1H,
d × quint, J 12.6 and 6.4) and 3.06 (1H, m).
(2R,4aS,5S,6S,8aS)-(؊)-3,4,4a,5,6,7,8,8a-Octahydro-6-
hydroxy-2,5,8a-trimethylnaphthalen-1(2H)-one 15
To sodium hydride washed with n-hexane (60% in mineral oil;
251 mg, 6.29 mmol) was added anhydrous methanol (10 cm3) at
0 ЊC under nitrogen atmosphere. A solution of decalones 13
and 14 (592 mg, 2.09 mmol) in methanol (10 cm3) was added
at 0 ЊC and the resulting solution was stirred at room tempera-
ture for 15.5 h. Reaction was quenched by addition of aq.
ammonium chloride. After extraction with ethyl acetate (×2),
the organic layer was washed with brine and dried over anhy-
drous Na2SO4. Evaporation of solvent followed by column
chromatography on silica gel (ethyl acetate–n-hexane 1:1)
provided decalone 15 (434 mg, 98%) as crystals; [α]D20 Ϫ37.6
(c 0.94, CHCl3); mp 75 ЊC; νmax/cmϪ1 3654, 2932, 1707, 1543,
1377 and 976; δH(200 MHz) 0.98 (3H, d, J 6.4), 1.01 (3H, d,
J 6.4), 1.14 (3H, s), 0.80–1.95 (10H, m), 2.10 (1H, m), 2.75
A stirred solution of mixture of 8 and 9 (1.00 g) and toluene-
p-sulfonic acid (PTSA) monohydrate (173 mg, 0.91 mmol) in
acetone (20 cm3) and water (4 cm3) was refluxed for 16 h. After
addition of aq. sodium hydrogen carbonate, product was
extracted with ethyl acetate (×2). The organic layer was washed
with brine and dried over anhydrous Na2SO4. Column chrom-
atography (ethyl acetate–n-hexane 1:2) gave 10 (727 mg, 83% in
two steps) and its isomer 11 (106 mg, 12% in two steps) as
crystals.
Compound 10 had [α]D23 Ϫ54.3 (c 0.388, CHCl3); mp 79 ЊC;
νmax/cmϪ1 3630, 2938, 1709, 1454, 1103, 1044 and 1022; δH(200
MHz) 1.03 (3H, d, J 6.4), 1.14 (3H, s), 1.19–2.30 (12H, m), 2.64
J. Chem. Soc., Perkin Trans. 1, 2000, 2645–2648
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(1H, d × quint, J 12.8 and 6.4) and 3.00–3.15 (1H, m) (Found:
the orange colour persisted. The reaction was quenched by addi-
C, 73.8; H, 10.4. Calc. for C13H22O2: C, 73.8; H, 10.5%).
tion of propan-2-ol. After extraction with ethyl acetate (×4),
combined organic layer was washed with brine (×2) and dried
over anhydrous Na2SO4. Evaporation of the solvent afforded
unstable (1ЈS,2R,2ЈS,6ЈS)-4-(2Ј-hydroxy-2Ј,6Ј-dimethyl-5Ј-oxo-
cyclohexyl)-2-methylbutanoic acid 1 (20 mg), δH(200 MHz) 0.8–
1.95 (10H, m), 1.07 (3H, d, J 6.1), 1.15 (3H, s), 1.2 (3H, d, J 7),
1.97–2.9 (4H, m) and 3.19 (1H, ddd, J 10.4, 9.5 and 4.9).
A solution of the acid 1 (20 mg) in ethyl acetate was treated
with an ethereal solution of diazomethane at 0 ЊC until the
yellow colour persisted. Evaporation of diethyl ether followed
by MPLC purification of the residue (ethyl acetate–n-hexane
10:1) provided ester 2 (13 mg, 52% from 17) as a colourless oil,
[α]D23 Ϫ13.1 (c 0.26, CHCl3) {natural product, [α]D23 Ϫ14.3 (c 0.28,
CHCl3)}; νmax/cmϪ1 3491, 2937, 1728, 1712, 1462, 1331, 1169,
1138 and 1092; δH(500 MHz) 1.13 (3H, d, J 7), 1.17 (3H, d, J 7),
1.24 (1H, m), 1.36 (3H, s), 1.44 (1H, ddd, J 10.5, 6.5 and 3.5),
1.58 (1H, m), 1.65 (1H, m), 1.74 (1H, br s), 1.76 (1H, m), 1.82
(1H, ddd, J 13, 11.5 and 6.0), 2.0 (1H, ddd, J 13.0, 6.5 and 4.5),
2.16 (1H, dq, J 10.5 and 7.5), 2.36 (1H, ddd, J 15.0, 11.5 and
6.5), 2.45 (1H, qdd, J 7.0, 3.5 and 3.5), 2.47 (1H, ddd, J 15.0, 6.0
and 4.5) and 3.68 (3H, s); δC(125 MHz) 13.9 (q), 17 (q), 22.4 (q),
27.9 (t), 33.7 (t), 37.7 (t), 39.6 (t), 39.8 (d), 47.4 (d), 52.6 (q), 53.9
(d), 72.5 (s), 177.2 (s) and 212 (s).
(2R,4aS,5S,6S,8aS)-(؊)-6-Acetoxy-3,4,4a,5,6,7,8,8a-octa-
hydro-2,5,8a-trimethylnaphthalen-1(2H)-one 16
A solution of the alcohol 15 (255 mg, 1.21 mmol), 4-(dimethyl-
amino)pyridine (DMAP) (18 mg, 0.147 mmol) and acetic
anhydride (0.36 cm3, 3.82 mmol) in pyridine (5 cm3) was stirred
at room temperature for 3.5 h. Water was added and stirring
was continued for 2 h. After extraction with ethyl acetate (×2),
the organic layer was washed with brine and dried over
anhydrous Na2SO4. Evaporation of the solvent followed by
silica gel column chromatography (ethyl acetate–n-hexane
1:2) provided acetate 16 (306 mg, 100%) as a colourless oil;
[α]D20 Ϫ5.43 (c 1.14, CHCl3); mp 71–72 ЊC; νmax/cmϪ1 2974, 1936,
1711, 1552, 1454, 1242, 1110, 1028 and 990; δH(200 MHz) 0.87
(3H, d, J 6.4), 0.99 (3H, d, J 6.4), 1.16 (3H, s), 1.28–2.28 (10H,
m), 2.06 (3H, s), 2.74 (1H, d × quint, J 12.8 and 6.4) and 4.35
(1H, m) (Found: C, 71.1; H, 9.65. Calc. for C15H24O3: C, 71.4;
H, 9.6%).
(1S,4R,7S,8S,9S)-(؉)-9-Acetoxy-1,4,8-trimethyl-2-oxabicyclo-
[5.4.0]undecan-3-one 17 and (1S,4R,7S,8S,9S)-(؉)-9-acetoxy-
1,4,8-trimethyl-3-oxabicyclo[5.4.0]undecan-2-one 18
A mixture of the decalone 16 (64 mg, 0.25 mmol) and MCPBA
(80%; 131 mg, 0.76 mmol) was stored at room temperature for
25 h under nitrogen atmosphere. The resulting mixture was
dissolved in ethyl acetate and the organic layer was washed suc-
cessively with aq. sodium hydrogen carbonate (×2), water and
brine. After being dried over anhydrous Na2SO4, the organic
layer was evaporated to dryness and MPLC purification of the
residue (ethyl acetate–n-hexane 1:2) gave lactones 17 (39 mg,
58%) and 18 (19 mg, 27%) as crystals.
Acknowledgements
We thank Profs. T. Hashimoto and Y. Asakawa, Tokushima
Bunri University, for providing spectral data of the ester 2.
References
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Compound 17 had [α]D20 ϩ3.92 (c 0.63, CHCl3), mp 139 ЊC;
νmax/cmϪ1 2936, 1732, 1385, 1359, 1240, 1201, 1115 and 1022;
δH(200 MHz) 0.93 (3H, d, J 5.9), 1.20 (3H, d, J 6.7), 1.52 (3H,
s), 1.30–2.20 (10H, m), 2.06 (3H, s), 2.58 (1H, m) and 4.46
(1H, m) (Found: C, 67.0; H, 9.1. Calc. for C15H24O4: C, 67.1; H,
9.0%).
Compound 18 had [α]D20 ϩ4.03 (c 0.83, CHCl3), mp 104–
105 ЊC; νmax/cmϪ1 2936, 1738, 1451, 1380, 1238, 1107, 1022 and
974; δH(200 MHz) 0.93 (3H, d, J 5.9), 1.32 (3H, s), 1.33 (3H, d,
J 6.2), 1.20–2.18 (10H, m), 2.06 (3H, s), 4.47 (1H, m) and 4.70
(1H, m).
10 R. M. Goodman and Y. Kishi, J. Am. Chem. Soc., 1998, 120, 9392.
11 J. J. P. Stewart, J. Comput. Chem., 1989, 10, 209.
12 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery, Jr.,
R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A. D.
Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S.
Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K.
Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B.
Foresman, J. Cioslowski, J. V. Ortiz, B. B. Stefanov, G. Liu,
A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin,
D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
C. Gonzalez, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen,
M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. S.
Replogle and J. A. Pople, Gaussian 98, Revision A.6, Gaussian
Inc., Pittsburgh, PA, USA, 1998.
Methyl (1ЈS,2R,2ЈS,6ЈS)-4-(2Ј-hydroxy-2Ј,6Ј-dimethyl-5Ј-oxo-
cyclohexyl)-2-methylbutanoate 2
A solution of the lactone 17 (26 mg, 0.096 mmol) in THF
(0.5 cm3) and 10% aq. sodium hydroxide (0.5 cm3) was stirred
at room temperature for 12 h. The reaction was quenched by
addition of dil. aq. hydrochloric acid. After extraction with
ethyl acetate (×4), the combined organic layer was washed with
brine (×2) and dried over anhydrous Na2SO4. Evaporation
of the solvent provided crude (1ЈS,2R,2ЈS,5ЈS,6ЈS)-4-(2Ј,5Ј-
dihydroxy-2Ј,6Ј-dimethylcyclohexyl)-2-methylbutanoic acid 19
(27 mg).
To a stirred solution of the dihydroxy acid 19 (27 mg) in
13 M.-C. Pierre, A. Tenaglia and M. Santelli, Tetrahedron, 1998, 54,
acetone (1 cm3) was added Jones reagent dropwise at 0 ЊC until
14803.
2648
J. Chem. Soc., Perkin Trans. 1, 2000, 2645–2648