Synthesis and olfactory evaluation of the enantiomerically enriched forms of 7,11-epoxymegastigma-5(6)-en-9-one and 7,11-epoxymegastigma-5(6)-en-9-ols isomers, identified in Passiflora edulis

Article abstract of DOI:10.1016/j.tetasy.2005.02.021

A study on the synthesis of the isomers of the natural C-13 norterpenoids derivatives 7,11-epoxymegastigma-5(6)-en-9-one and 7,11-epoxymegastigma-5(6)-en- 9-ols is reported. The latter compounds were prepared from readily available racemic α-ionone and then resolved by mean of lipase-mediated acetylation. The obtained enantiomerically forms were evaluated for their odour properties.

Full text of DOI:10.1016/j.tetasy.2005.02.021

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1699–1704
Synthesis and olfactory evaluation of the enantiomerically
enriched forms of 7,11-epoxymegastigma-5(6)-en-9-one and
7,11-epoxymegastigma-5(6)-en-9-ols isomers, identified in
Passiflora edulis
Elisabetta Brenna, Claudio Fuganti and Stefano Serra*
C.N.R., Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘Adolfo Quilico’ presso Dipartimento di Chimica,
Materiali ed Ingegneria Chimica ‘Giulio Natta’ del Politecnico, Via Mancinelli 7, I-20133 Milan, Italy
Received 14 February 2005; accepted 21 February 2005
Available online 18 March 2005
Abstract—A study on the synthesis of the isomers of the natural C-13 norterpenoids derivatives 7,11-epoxymegastigma-5(6)-en-
9-one and 7,11-epoxymegastigma-5(6)-en-9-ols is reported. The latter compounds were prepared from readily available racemic
a-ionone and then resolved by mean of lipase-mediated acetylation. The obtained enantiomerically forms were evaluated for their
odour properties.
ꢀ 2005 Elsevier Ltd. All rights reserved.
O
OH
1. Introduction
OH
8
9
7
10
Many flavours occur in nature as a mixture of stereo-
isomers. The sensorial properties of these compounds
are frequently related with their isomeric composition
and several aspects of enantioselective perception of chi-
ral odorants have been reported.1 Therefore, the prepa-
ration of flavours and fragrances as pure stereoisomers
has attracted much attention. In this context, we have
been working on the enantioselective preparation of
different natural norterpenoids compounds such as
ionones2 and irones3 isomers.
6
1
4
2
O
O
O
3
5
11
1
2
3
Figure 1.
prepared by chemical synthesis allowing structure 1
and the relative configuration of 2 to be assigned to
the natural products. Afterwards, 1 was found by Kai-
ser5 to be present in very high amounts in the headspace
of the strong ionone floral smelling of the rare terrestrial
orchid Houlletia odoratissima (Linden) and also in the
scent of the orchidaceae Gongora cruciformis (Whitten
and Bennett).6 In all cases the paucity of the natural
compounds and the lacking of enantiopure reference
materials precluded the measurement of its enantiomeric
composition. To the best of our knowledge, no enantio-
selective synthesis of compounds 1–3 has been reported
to date. Herein we report on the preparation of com-
pound 1–3 starting from readily available racemic a-ion-
one. The compounds were synthesized in racemic form
and then were resolved by mean of lipase-mediated
acetylation. The odour properties of the enantiomer-
enriched forms were evaluated and described by exper-
tise perfumers.
We herein report on the synthesis and olfactory evalua-
tion of the isomers of the C-13 norterpenoids derivatives
7,11-epoxymegastigma-5(6)-en-9-one and 7,11-epoxy-
megastigma-5(6)-en-9-ols. The latter compounds are
unusual bicyclic ionone derivatives formally obtained
by the oxidation of the C(11) carbon atom and ring clo-
sure between positions 7 and 11 of the ionone frame-
work (Fig. 1). These were first described by Na¨f et al.4
in 1977 as components of the volatiles of the purple-
skinned passion fruit (Passiflora edulis Sims). In order
to corroborate the structures, these compounds were
*
Corresponding author. Tel.: + 39 2 2399 3076; fax: + 39 2 2399
3080; e-mail: stefano.serra@polimi.it
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.02.021

1700
E. Brenna et al. / Tetrahedron: Asymmetry 16 (2005) 1699–1704
2. Results and discussion
2.2. Lipase-mediated resolution of 7,11-epoxymega-
stigma-5(6)-en-9-ols 2 and 3
2.1. Preparation of racemic 7,11-epoxymegastigma-5(6)-
en-9-one 1
With an effective synthetic method to 1 in hand, the
next stepwas the preparation and the resolution of
alcohols 2 and 3. The reduction of 1 with NaBH4 in
methanol gave a 70:30 mixture of diastereoisomers 2
and 3, respectively. The latter was easily separated by
chromatography and then submitted to lipase-mediated
kinetic acetylation using vinyl acetate as an acyl donor
As part of a program on the preparation of enantiopure
odorants, we have previously shown the efficiency of
lipase-mediated kinetic resolutions of racemic materi-
als.7 The latter approach has been successfully applied
in the preparation of enantiomerically enriched ionone2
and irone3 isomers by mean of acetylation of racemic io-
nols and irols, respectively. Accordingly, we extended
this flexible enzymic methodology to the resolution of
7,11-epoxymegastigma-5(6)-en-9-one derivative. Our
study first needed a valuable amount of racemic starting
materials. The previous preparation of 1 is based on the
regioselective epoxidation of racemic c-ionone followed
by base-promoted isomerization. Racemic 1 was there-
fore obtained regioselectively in only two steps. In spite
of these advantages, c-ionone is not commercially avail-
able and should be prepared by synthesis.8 Therefore,
we amended this unfavourable aspect by some modifica-
tion to the latter synthetic pathway. Our approach starts
from the inexpensive and commercially available a-
ionone (Scheme 1) that was reduced and converted in
the a-ionol acetate 4. According to a procedure we
previously developed for c-irone synthesis,9 the latter
compound was irradiated in quartz vessels, with high-
pressure Hg lamps. By this mean, the endo-cyclic double
bond of the a-ionol framework was isomerized to the
exo-cyclic double bond of the c-ionol derivatives.
Acetate 4 was smoothly converted into a 2:1 mixture
of c-ionol acetate isomers 5 and 6, respectively. The con-
comitant isomerization of the conjugated double bond
does not effect the overall efficiency of the process since
during the ring closure step, both regioisomers give 1.
Therefore, acetates 5 and 6 were not separated and were
converted to c-ionone isomers 7 and 8 by saponification
of the acetate and oxidation. The epoxidation of the
latter mixture with MCPBA afforded a mixture of four
isomers with chemical structure 9 and 10. According
to Na¨fꢀs procedure, the latter compounds were
treated with sodium methylate in DMF to give 7,11-
epoxymegastigma-5(6)-en-9-one 1 in a regioselective
fashion.
t
and BuOMe as solvent (Scheme 2). We selected lipase
PS as catalyst since this enzyme gave the best perfor-
mances in terms of enantioselectivity in the ionol and
irol resolutions. Using the above-mentioned experimen-
tal conditions, ( )-2 gave acetate (+)-11 (97% ee) and
unreacted alcohol (ꢀ)-2 (97% ee), as well as ( )-3 gave
acetate (ꢀ)-12 (99% ee) and unreacted alcohol (+)-3
(90% ee). The latter compounds were separated by
chromatography and acetates (+)-11 and (ꢀ)-12 were
saponificated to give alcohols (+)-2 and (ꢀ)-3, respec-
tively. All the isomeric forms of epoxymegastigma-
5(6)-en-9-ols 2 and 3 were therefore obtained. The
enantiomeric forms of 1 were then prepared by PyÆSO3
oxidation.10 Transformation of (ꢀ)-2 or (ꢀ)-3 gave
(ꢀ)-1 whereas transformation of (+)-2 or (+)-3 gave
(+)-1.
The assignment of the absolute configuration of these
compounds needs further consideration. The chemical
correlation with compounds of known stereochemistry
was not possible due to the singularity of the latter struc-
ture and consequently the lack of data. The transform-
ation of the isomeric forms of alcohols 2 and 3 into
the corresponding p-bromobenzoate derivatives did
not afford crystalline materials precluding the possibility
of X-ray analysis. Therefore, we assigned the absolute
configuration of the alcohols by a less rigorous method.
We have previously demonstrated that lipase PS cataly-
ses enantioselectively the acetylation of the alcohol with
chemical structure relate to ionol11 and dihydroionol.12
This process affords invariably the corresponding (9R)-
acetate. According to the latter finding, the stereochem-
istry of acetate (+)-11 and (ꢀ)-12 should be (7S,9R) and
(7R,9R), respectively. Consequently, we assigned to
compounds (+)-1, (ꢀ)-1, (ꢀ)-2, (+)-2, (+)-3 and (ꢀ)-3
OAc
OAc
OAc
i,ii
iv, v
iii
Racemic
α-ionone
+
4
5
6
O
O
O
O
O
vii
vi
+
O
+
O
O
7
9
10
( )-1
8
Scheme 1. Synthesis of racemic 7,11-epoxymegastigma-5(6)-en-9-one 1. Reagents and conditions: (i) NaBH4, MeOH; (ii) Ac2O, Py; (iii) hm, iPrOH,
xylene; (iv) KOH, MeOH; (v) MnO2, CHCl3; (vi) MCPBA, CH2Cl2; (vii) NaOMe, DMF.

E. Brenna et al. / Tetrahedron: Asymmetry 16 (2005) 1699–1704
1701
OH
OH
( )-1
i
O
O
( )-2
( )-3
ii
ii
OAc
OH
OH
OAc
+
O
O
O
O
+
(–)-2
(+)-11
(–)-12
iii
(+)-3
iii
iv
OH
O
O
OH
iv
iv
O
O
O
O
(+)-2
(+)-1
(–)-1
(–)-3
Scheme 2. Lipase PS-mediated resolution of 7,11-epoxymegastigma-5(6)-en-9-one 1 and 7,11-epoxymegastigma-5(6)-en-9-ols 2 and 3. Reagents and
conditions: (i) NaBH4, MeOH; (ii) lipase PS, vinyl acetate, t-butylmethylether; (iii) KOH, MeOH; (iv) PyÆSO3, DMSO, Et3N.
absolute configurations (7S), (7R), (7R,9S), (7S,9R),
(7S,9S) and (7R,9R), respectively.
The obtained enantiomerically enriched forms were
evaluated and their odour properties described. The
absolute configuration of the latter compounds were
assigned.
2.3. Olfactory evaluation
All the enantiomerically enriched forms of 7,11-epoxy-
megastigma-5(6)-en-9-one and 7,11-epoxymegastigma-
5(6)-en-9-ols isomers were evaluated by qualified
perfumers (Givaudan Schweiz AG). The results are
shown in Table 1 and indicate some considerations.
The evaluated compounds could be included in the class
of floral odorants. In terms of intensity, there is not a
great difference between the ketonic and alcoholic
compounds: both ketone 1 and alcohols 2 and 3 are
essentially weak. Otherwise, in terms of quality, the
latter two classes of compounds show certain distinc-
tions. Some differences in the odour features were
anyway detected either between diastereoisomers or
enantiomers.
4. Experimental
4.1. General
All solvents and reagents were purchased from suppliers
and used without further purification. H NMR spectra
1
were recorded in a CDCl3 solution at room temperature
unless otherwise stated, on a Bruker AC-250 spectro-
meter (250 MHz H). The chemical-shift scale is based
1
on internal tetramethylsilane. IR spectra were recorded
on a Perkin–Elmer 2000 FTIR spectrometer. Mass spec-
tra were measured on a Finnigan-MAT TSQ 70 spec-
trometer. Melting points were measured on a Reichert
melting-point apparatus, equipped with a Reichert
microscope, and are uncorrected. Optical rotations were
determined on a Propol automatic digital polarimeter.
TLC analyses were performed on Merck Kieselgel 60
F254 plates. Microanalyses were determined on an ana-
lyzer 1106 from Carlo Erba. All the chromatographic
separations were carried out on silica gel columns.
Lipase PS from it Pseudomonas cepacia (Amano Phar-
maceuticals Co., Japan) was employed. GC analyses:
3. Conclusions
The natural C-13 norterpenoids 7,11-epoxymegastigma-
5(6)-en-9-one and 7,11-epoxymegastigma-5(6)-en-9-ols
were prepared from the easily available racemic a-
ionone. These racemic compounds were resolved for
the first time by mean of lipase-mediated acetylation.
Table 1. Olfactory evaluation of 7,11-epoxymegastigma-5(6)-en-9-one and 7,11-epoxymegastigma-5(6)-en-9-ols isomers
Compound
Odour description
(ꢀ)-1
(+)-1
(ꢀ)-2
(+)-2
(ꢀ)-3
(+)-3
Sweet, food-like, slightly vanillic note
Weak, somewhat floral-fruity, raspberry, ionone-like
Weak, floral-fruity, with a woody, cardboard-like nuance and some metallic facets
Weak, citric, acidic, slightly floral
Weak, citric, acidic, with a sweet floral touch
Weak, floral smell with technical, acidic component, a bit in the direction of rice wine

1702
E. Brenna et al. / Tetrahedron: Asymmetry 16 (2005) 1699–1704
HP-6890 gas chromatograph; determined on a HP-5
column (30 m · 0.32 mm; Hewlett Packard) with the fol-
lowing tempprogram 60 ꢁ (1 min)–6ꢁ/min–150ꢁ (1 min)–
12ꢁ/min–280ꢁ (5 min); tR given in minutes. Chiral GC
analyses: DANI-HT-86.10 gas chromatograph; enantio-
meric excesses of compound 1 determined on a
DACTBS BETA (MEGA, Italy)-Column with the fol-
lowing tempprogram 60 ꢁ (3 min)–3ꢁ/min–180ꢁ (5 min);
enantiomeric excesses of compound 2 determined by
oxidation to compound 1 followed by chiral GC analy-
ses; enantiomeric excesses of compound 3 determined on
a CHIRASIL DEX CB-Column with the following
temprpogram 40 ꢁ (3 min)–1.5ꢁ/min–180ꢁ (5 min); tR
given in minutes.
A solution of the above mentioned mixture (28 g) in
CH2Cl2 (150 cm3) was treated with MCPBA (28 g,
162 mmol) stirring at 0 ꢁC until no more starting ionone
was detected by TLC analysis (4 h). The MCBA was
eliminated by filtration and the solution was washed in
turn with saturated NaHCO3 solution (100 cm3) and
5% aq, Na2SO3 (150 cm3). The organic layer was dried
(Na2SO4), concentrated under reduced pressure and
the residue was dissolved in dry DMF (100 cm3). The
obtained solution was treated with NaOMe (8 g,
148 mmol) stirring at rt for 3 h. After this time, the reac-
tion was quenched by the addition of water (200 cm3)
and extraction with diethyl ether (3 · 100 cm3). The
organic phase was washed in turn with water (80 cm3)
and brine (100 cm3), then dried over Na2SO4 and con-
centrated in vacuo. The residue was purified by chroma-
tography (hexane!hexane/ethyl acetate 7:3) to afford
pure 1 (oil, 18.9 g, 72% two steps) (GC analysis: tR
19.37, 98%). FT-IR (film) 1716, 1457, 1363, 1234,
1158, 1070, 1040, 1020, 914, 881; m/z (EI): 208 (M+,
8), 193 (32), 165 (5), 151 (43), 150 (99), 135 (100), 123
(13), 107 (18), 95 (16), 91 (15), 81 (28), 69 (7), 55 (6); d
1.04 (3H, s, Me–C(1)), 1.05 (3H, s Me–C(1)), 1.29–
1.55 (2H, m), 1.65–1.78 (2H, m), 1.88–2.00 (2H, m)
(CH2(2), CH2(3), CH2(4)), 2.23 (3H, s, Me(10)), 2.60
(1H, dd, J 9.5 and 14.5, H–C(8)), 2.72 (1H, dd, J 3.4
and 14.5, H–C(8)), 4.37 (1H, dm, J 12 H–C(11)), 4.51
(1H, ddt, J 12, 5 and 1.2, H–C(11)), 5.21 (1H, m, H–
C(7)). Anal. Calcd for C13H20O2: C, 74.96; H, 9.68.
Found: C, 75.05; H, 9.70.
4.2. Synthesis of racemic 7,11-epoxymegastigma-5(6)-
en-9-one 1
A solution of a-ionone (40 g, 208 mmol) in methanol
(200 cm3) was cooled to 0 ꢁC and treated under stirring
with NaBH4 (4 g, 106 mmol). After 2 h the reaction was
diluted with water (500 cm3), 5% HCl aq (200 cm3) and
extracted with ether (3 · 150 cm3). The combined organ-
ic phases were washed with brine (100 cm3), dried over
Na2SO4 and concentrated under reduced pressure. The
residue was then treated with pyridine (50 cm3) and
Ac2O (50 cm3). When the acetylation was complete
(6 h) the mixture was concentrated under reduced pres-
sure and the residue was purified by chromatography
(hexane!hexane/ethyl acetate 9:1) to afford pure ionol
acetate 4 (44.9 g, 91%) as a 1:1 mixture of diastereoiso-
mers (GC analysis: tR 16.66 and 16.76).
4.3. Synthesis of racemic 7,11-epoxymegastigma-5(6)-
en-9-ols 2 and 10
A solution of 4 (42 g, 178 mmol) in isopropanol
(250 cm3) in the presence of xylene (50 cm3) as the pho-
tosensitizer was irradiated in quartz vessels, in a Ray-
onet photochemical reactor equipped with 10 8-W
high-pressure Hg lamps. The reaction was monitored
by GC analysis and the irradiation interrupted until
compound 4 became less than 5% of the mixture
(20 days). The solution was then concentrated under re-
duced pressure to afford an oil that showed the follow-
ing composition: compound 5 (59%, 1:1 mixture of
diastereoisomers, tR 17.06 and 17.14), compound 6
(29%, 1:1 mixture of diastereoisomers, tR 16.45 and
16.56), compound 4 (4%, 1:1 mixture of diastereoiso-
mers) and a mixture of unidentified compound (8%).
A solution of compound 1 (16 g, 77 mmol) in methanol
(80 cm3) was cooled to 0 ꢁC and treated under stirring
with NaBH4 (1.5 g, 40 mmol). After 2 h the reaction
was diluted with water (150 cm3), 5% HCl aq (50 cm3)
and extracted with ether (3 · 100 cm3). The combined
organic phases were washed with brine (100 cm3), dried
over Na2SO4 and concentrated under reduced pressure.
The residue was purified by chromatography eluting
with hexane/ethyl acetate (95:5!70:30) to afford pure
2 (first eluted diastereoisomer, oil, 10.2 g, 63%) (GC
analysis: tR 19.40, 99%). FT-IR (film) 3490, 1456,
1425, 1362, 1300, 1134, 1072, 1020, 947, 829; m/z (EI):
211 (M++1, 2), 210 (M+, 13), 192 (22), 177 (26), 163
(3), 152 (14), 151 (100), 135 (12), 133 (19), 123 (12),
109 (14), 107 (14), 95 (22), 81 (38), 69 (8), 67 (8), 55
(8); d 1.03 (3H, s, Me–C(1)), 1.06 (3H, s Me–C(1)),
1.20 (3H, d, J 6.2 Me(10)), 1.30–1.57 (3H, m), 1.65–
1.78 (2H, m), 1.82 (1H, dt, J 14 and 2.3) 1.88–2.02
(2H, m) (CH2(2), CH2(3), CH2(4), CH2(8)), 3.76 (1H,
br s, OH), 4.00–4.15 (1H, m H–C(9)), 4.39 (1H, ddt, J
11.7, 2.6 and 1.1, H–C(11)), 4.54 (1H, ddt, J 11.7, 5.1
and 1.1, H–C(11)), 4.97 (1H, m, H–C(7)). Anal. Calcd
for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.30; H,
10.50. The second eluted diastereoisomer was pure 3
(oil, 4.5 g, 28%), (GC analysis: tR 19.29, 98%). FT-IR
(film) 3431, 1457, 1363, 1128, 1065, 1020, 942, 843;
m/z (EI): 211 (M++1, 3), 210 (M+, 16), 192 (24), 177
(32), 163 (4), 152 (15), 151 (100), 135 (18), 133 (18),
123 (13), 109 (16), 107 (16), 95 (24), 81 (40), 69 (8), 67
The above mentioned oil in methanol (100 cm3) was trea-
ted with a solution of KOH (12 g, 214 mmol) in metha-
nol (80 cm3) stirring at rt until no more starting acetate
was detected by TLC analysis. The mixture was diluted
with water (300 cm3) and extracted with diethyl ether
(3 · 150 cm3). The combined organic phases were
washed with brine, dried over Na2SO4 and concentrated.
The residue was dissolved in CHCl3 (200 cm3) and trea-
ted with MnO2 (30 g, 345 mmol) stirring at reflux for 6 h.
The mixture was then cooled, filtered and the organic
phase concentrated under reduced pressure to afford an
oil (29.2 g) that showed the following composition (GC
analysis): compound 7 (60%, tR 16.28), compound 8
(26%, tR 14.82), a-ionone (4%, tR 16.06) and a mixture
of unidentified compound (10%).

E. Brenna et al. / Tetrahedron: Asymmetry 16 (2005) 1699–1704
1703
(7), 55 (8); d 1.03 (3H, s, Me–C(1)), 1.04 (3H, s Me–
C(1)), 1.21 (3H, d, J 6.3 Me(10)), 1.25–1.56 (2H, m),
1.64–1.79 (3H, m) 1.81–2.07 (3H, m) (CH2(2), CH2(3),
CH2(4) CH2(8)), 3.20 (1H, br s, OH), 3.96–4.10 (1H,
m H–C(9)), 4.39 (1H, ddt, J 11.7, 3.4 and 1.1, H–
C(11)), 4.54 (1H, ddt, J 11.7, 5.3 and 1.1, H–C(11)),
5.12 (1H, m, H–C(7)). Anal. Calcd for C13H22O2: C,
74.24; H, 10.54. Found: C, 74.35; H, 10.50.
(42), 135 (31), 133 (10), 121 (12), 107 (17), 95 (12), 81
(21), 69 (10), 55 (6); d 1.05 (3H, s, Me–C(1)), 1.08 (3H,
s Me–C(1)), 1.27 (3H, d, J 6.2 Me(10)), 1.29–1.60 (3H,
m), 1.64–1.74 (2H, m) 1.85–2.07 (3H, m) (CH2(2),
CH2(3), CH2(4) CH2(8)), 2.04 (3H, s, OCOMe), 4.34
(1H, dm, J 11.7, H–C(11)), 4.46 (1H, ddt, J 11.7, 4.8
and 1.3, H–C(11)), 4.81 (1H, m, H–C(7)), 5.15 (1H, m,
H–C(9)). Anal. Calcd for C15H24O3: C, 71.39; H, 9.59.
Found: C, 71.30; H, 9.55. Alcohol (+)-3 (oil, 98%
4.4. Lipase PS-mediated resolution of the racemic
substrates
GC); bp(oven tempbulb-to-bulb distillation) 90–
20
95 ꢁC/0.05 mmHg; ½aŠ ¼ þ55:2 (c 2, CHCl3); chiral
D
GC (tR 59.17) ee = 90%, IR, H NMR, MS: in accor-
dance with that of ( )-3. Saponification of the acetate
1
4.4.1. General procedure. A mixture of the suitable
racemic substrate (3 g, 14.3 mmol), lipase PS (1.5 g),
20
(ꢀ)-12 gave pure (ꢀ)-3 (98% GC), ½aŠ ¼ ꢀ64:7 (c 2,
D
CHCl3); bp(oven tempbulb-to-bulb distillation) 90–
t
vinyl acetate (5 cm3) and BuOMe (30 cm3) was stirred at
rt and the formation of the acetate monitored by TLC
analysis. The reaction was stopped at about 50% conver-
sion by filtration of the enzyme and evaporation of the
solvent at reduced pressure. The residue was purified
by chromatography eluting with hexane–ethyl acetate
(95:5!70:30) to give the alcohol acetate and unreacted
alcohol. The acetate was then dissolved in methanol
(10 cm3) and treated with KOH (1 g, 18 mmol) in meth-
anol (10 cm3) and stirring continued at rt until no more
starting material was detected by TLC analysis. The
mixture was diluted with water (60 cm3) and extracted
with diethyl ether (3 · 50 cm3). The organic phase was
washed with brine, dried (Na2SO4) and concentrated
in vacuo. The residue was purified by chromatography
and bulb-to-bulb distillation to give the enantiomeric
form of the unreacted alcohol.
95 ꢁC/0.05 mmHg; mp42–44 ꢁC; chiral GC (tR 59.52)
ee >99%, IR, H NMR, MS: in accordance with that
of ( )-3.
1
4.5. Preparation of (+)- and (ꢀ)-7,11-epoxymegastigma-
5(6)-en-9-one 1
A
solution of the pyridine–SO3 complex (1.6 g,
10 mmol) in DMSO (10 cm3) was added dropwise to a
stirred mixture of alcohol (+)-2 (1 g, 4.8 mmol), DMSO
(15 cm3) and triethylamine (5 cm3, 36 mmol). The tem-
perature was maintained below 30 ꢁC and the reaction
continued until no more starting alcohol was detected
by TLC analysis (3 h). The mixture was then diluted
with water (100 cm3), acidified with 5% HCl aq
(50 cm3) and extracted with diethyl ether (3 · 50 cm3).
The combined organic phases were washed with brine,
dried over Na2SO4 and concentrated under reduced
pressure. The residue was purified by chromatography
4.4.2. Resolution of racemic 2. Racemic 2 was resolved
according to the general procedure to give acetate (+)-11
(oil, 98% GC, tR 21.33); bp(oven tempbulb-to-bulb dis-
(hexane!hexane/ethyl acetate 7:3) to afford pure (+)-1
20
20
(oil, 0.93 g, 93%) (GC analysis: 98%); ½aŠ ¼ þ158:2 (c
tillation) 95–100 ꢁC/0.02 mmHg; ½aŠ ¼ þ77:1 (c 2,
D
D
CHCl3); FT-IR (film) 1736, 1458, 1368, 1244, 1075,
1060, 1020, 955, 863; m/z (EI): 252 (M+, 4), 209
(M+ꢀOAc, 1), 192 (76), 177 (88), 163 (9), 151 (100),
135 (48), 133 (21), 122 (16), 107 (20), 95 (21), 81 (39),
69 (16), 55 (8); d 1.03 (3H, s, Me–C(1)), 1.07 (3H, s
Me–C(1)), 1.31 (3H, d, J 6.3 Me(10)), 1.32–1.54 (2H,
m), 1.64–1.78 (2H, m) 1.80–1.97 (4H, m) (CH2(2),
CH2(3), CH2(4) CH2(8)), 2.02 (3H, s, OCOMe), 4.34
(1H, dm, J 11.7, H–C(11)), 4.51 (1H, dd, J 11.7 and
5.1, H–C(11)), 4.83 (1H, m, H–C(7)), 5.11 (1H, m, H–
C(9)). Anal. Calcd for C15H24O3: C, 71.39; H, 9.59.
Found: C, 71.45; H, 9.60. Alcohol (ꢀ)-2 (oil, 97% GC);
2, CHCl3); chiral GC (tR 29.02) ee = 97%; IR, 1H
NMR, MS: in accordance with that of ( )-1.
The above described method was applied to the oxida-
tion of the following alcohols:
20
(ꢀ)-3 to give (ꢀ)-1 (90%) ½aŠ ¼ ꢀ158:8 (c 2, CHCl3);
D
1
chiral GC (tR 29.64) ee >99%, IR, H NMR, MS: in
accordance with that of ( )-1.
20
(ꢀ)-2 to give (ꢀ)-1 (94%) ½aŠ ¼ ꢀ154:1 (c 2, CHCl3);
D
1
chiral GC ee = 97%, IR, H NMR, MS: in accordance
bp(oven tempbulb-to-bulb distillation) 90–95
ꢁC/
with that of ( )-1.
20
0.05 mmHg; ½aŠ ¼ ꢀ69:5 (c 2, CHCl3); ee = 97%, IR,
D
20
(+)-3 to give (+)-1 (91%) ½aŠ ¼ þ145:2 (c 2, CHCl3);
1H NMR, MS: in accordance with that of ( )-2. Sapon-
ification of the acetate (+)-11 gave pure (+)-2 (oil, 98%
D
1
chiral GC ee = 90%, IR, H NMR, MS: in accordance
20
D
GC), ½aŠ ¼ þ72:5 (c 2, CHCl3); bp(oven tempbulb-
with that of ( )-1.
to-bulb distillation) 90–95 ꢁC/0.05 mmHg ee = 97%,
IR, H NMR, MS: in accordance with that of ( )-2.
1
Acknowledgements
4.4.3. Resolution of racemic 3. Racemic 3 was resolved
according to the general procedure to give acetate (ꢀ)-
20
The authors would like to thank Dr. PhilipKraft and
Dr. Roman Kaiser (Givaudan Schweiz AG) for the
odour descriptions and for the information about
natural 7,11-epoxymegastigma-5(6)-en-9-one, respectively.
The financial support of COFIN-MURST is also
acknowledged.
12 (oil, 98% GC, tR 21.10); bp(oven tempbulb-to-bulb
distillation) 95–100 ꢁC/0.02 mmHg; ½aŠ ¼ ꢀ93:9 (c 2,
D
CHCl3); ee >99%, FT-IR (film) 1735, 1457, 1372,
1243, 1136, 1063, 1021, 954, 860; m/z (EI): 252 (M+,
2), 209 (M+ꢀOAc, 1), 192 (77), 177 (100), 163 (8), 151

1704
E. Brenna et al. / Tetrahedron: Asymmetry 16 (2005) 1699–1704
France, September 5–7, 1996, Rivista Italiana EPPOS,
1997; pp 17–47.
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