Total Synthesis of the Marine Sesquiterpenoid Raikovenal through a Novel Utilization of the Bicycloheptenone Approach

Full text of DOI:10.1021/jo972098e

J . Org. Chem. 1998, 63, 2389-2391
2389
Sch em e 1. Th e Tota l Syn th esis of Ma r in e
Sesqu iter p en oid Ra ik oven a l th r ou gh th e
Bicyclo[3.2.0]h ep ten on e Ap p r oa ch
Tota l Syn th esis of th e Ma r in e
Sesqu iter p en oid Ra ik oven a l th r ou gh a
Novel Utiliza tion of th e
Bicyclo[3.2.0]h ep ten on e Ap p r oa ch
Goffredo Rosini,* Fabio Laffi, Emanuela Marotta,
Ilaria Pagani, and Paolo Righi
Dipartimento di Chimica Organica “A. Mangini”
dell’Universita`-Viale del Risorgimento n. 4,
I-40136-Bologna, Italy
Received November 17, 1997
In tr od u ction
In 1994, Pietra and co-workers1 isolated from the
marine ciliate Euplotes raikovi Amagaliev, stock Morl,
collected along Atlantic coasts near Casablanca, the
architecturally unusual sesquiterpenoid 1 termed raiko-
venal and its putative biogenetic precursor (preraikove-
nal). The structure and relative stereochemistry of 1
were deduced on the basis of extensive NMR studies. The
main part of the molecular array is the bicyclo[3.2.0]-
heptane core with the five-carbon side chain, the hy-
droxylated R,â-unsaturated aldehyde, in a strictly defined
geometric setting.
Whereas the effectiveness of raikovenal in favoring
adaptive radiation of marine ciliate E. raikovi was clearly
demonstrated,1 no synthesis of this interesting marine
natural product has been reported until now.
Recently, an efficient approach to the stereoselective
synthesis of natural products based on the practical
preparation and selective utilization of bicyclo[3.2.0]hept-
3-en-6-ones2,3 has been devised and developed in our
laboratories. In this paper we present (Scheme 1) the
stereoselective synthesis of racemic raikovenal through
the application of this bicyclization methodology.
which can be prepared by bismethylation of 3.2 It is
relevant to point out that racemic 4-methylbicyclo[3.2.0]-
hept-3-en-6-one (3) as well as racemic filifolone (5) have
been efficiently resolved into their enantiomerically pure
forms,7 thus allowing this strategy to be applicable to the
synthesis of both enantiomers of raikovenal.
Resu lts a n d Discu ssion
Carbonyl homologation of 6 to obtain the aldehyde 8
was revealed to be the crucial step of our synthetic
sequence. This conversion was achieved by reaction at
low temperature of the bicyclic ketone 6 with the in-situ
generated (methoxy(trimethylsilyl)methyl)lithium8 (MT-
MSMLi, Magnus reagent) followed by treatment of the
diastereoisomeric â-alkoxysilane intermediates with thi-
onyl chloride and pyridine. The diastereoisomeric enol
ethers 7 were isolated in only a 45% yield and almost
quantitatively converted into a mixture of bicyclic alde-
hydes 8 (exo/endo ) 4:1) by hydrolysis with formic acid.
The low yield of the carbonyl homologation can be
ascribed to two concomitant factors: the hampering effect
Our synthetic approach starts with 4-methylbicyclo-
[3.2.0]hept-3-en-6-one (3), easily available in nearly 80%
yield by the intramolecular bicyclization of 3-hydroxy-3-
methyl-6-heptenoic acid.3,4 The palladium-catalyzed hy-
drogenation of compound 3 followed by bismethylation
of the C7 gave the 4-endo-7,7-trimethylbicyclic derivative
6 in 71% yield. Alternatively, compound 6 can be
obtained by palladium-catalyzed hydrogenation of fili-
folone5,6 (4,7,7-trimethylbicyclo[3.2.0]hept-3-en-6-one, 5)
* Corresponding author: phone, +39 51 644 3640. fax +39 51 644
3654. e-mail: rosini@ms.fci.unibo.it.
(1) Guella, G.; Dini, F.; Erra, F.; Pietra, F. J . Chem. Soc. Chem.
Commun. 1994, 2585. Guella, G.; Dini, F.; Pietra, F. Helv. Chim. Acta
1995, 78, 1747.
(2) The approach has been used in the stereoselective total synthesis
of racemic grandisol and lineatin: Confalonieri, G.; Marotta, E.; Rama,
F.; Righi, P.; Rosini, G.; Serra, R.; Venturelli, F. Tetrahedron 1994,
50, 3235 and in the preparation of several intermediates in Curran’s
synthesis of linear condensed sesquiterpenes: Marotta, E.; Righi, P.;
Rosini, G. Tetrahedron Lett. 1994, 35, 2949.
(3) For more details of the general methodology used to prepare
substituted bicyclo[3.2.0]hept-3-en-6-ones, see: Rosini, G.; Confalonieri,
G.; Marotta, E.; Rama, F.; Righi, P. Org. Synth. 1997, 74, 158 and
references therein.
(5) Filifolone (4,7,7-trimethylbicyclo[3.2.0]hept-3-en-6-one), the first
monoterpene reported to have the bicyclo[3.2.0]heptane ring, was
isolated always in scalemic mixtures: D-filifolone from the Australian
plant Zieria smithii Andrews, and L-filifolone in the Arizonan sage
Artemisia filifolia Torrey: Torrance, S. J .; Steelink, C. J . Org. Chem.
1974, 39, 1068.
(6) The synthesis of filifolone has been accomplished following
several different approaches: see Stadler, H.; Rey, M.; Dreiding, A.
Helv. Chim. Acta 1984, 67, 1854.
(7) Marotta, E.; Pagani, I.; Righi, P., Rosini, G. Tetrahedron:
Asymmetry 1995, 6, 2319.
(8) Magnus, P.; Roy, G. Organometallics 1982, 1, 553.
(4) Marotta, E.; Pagani, I.; Righi, P.; Rosini, G. Tetrahedron 1994,
50, 7645.
S0022-3263(97)02098-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/04/1998

2390 J . Org. Chem., Vol. 63, No. 7, 1998
Notes
of the geminal methyls on the carbon adjacent to the
carbonyl group that amplify the hindrance due to the
wedge shape of the bicyclic compound, and the tendency
of the intermediates to undergo fragmentations and
rearrangements through the formation of unstable ter-
tiary carbon ions.
Exp er im en ta l Section
Gen er a l. Melting points were obtained with a Bu¨chi ap-
paratus and are uncorrected. Yields refer to isolated products.
Proton and 13C NMR spectra were recorded at 300 and 75.4
MHz, respectively, in CDCl3 solvent. Chemical shifts are
expressed in ppm downfield from TMS as internal standard, and
coupling constants are reported in hertz. Signal multiplicities
were established by DEPT experiments. Flash chromatographic
separations were performed using Merck silica gel 60 (70-230
mesh ASTM). For thin-layer chromatography (TLC) analysis
throughout this work, Merck precoated TLC plates (silica gel
60 GF254, 0.25 mm) were used. All solvents were dried and
purified by standard methods prior to use. Reactions involving
alkyllithiums and DIBAH were run under argon or nitrogen.
Compounds 3 and 5 were prepared following the procedures
already reported.3,4
We chose the Horner-Wadsworth-Emmons9 (HWE)
modification introduced by Masamune, Roush et al.10 to
perform the olefination of the aldehydes 8 with the
γ-butyrolactone residue to complete the building of the
raikovenal skeleton. This modification has been depicted
as particularly useful in reactions with aldehydes or
phosphonates that can undergo epimerization or aldol-
type reactions under standard conditions to furnish
products with a high (E)-selectivity. Actually, when the
mixture of the aldehydes 8 was treated with γ-butyro-
lactone-R-diethylphosphonate11 in tetrahydrofuran in the
presence of LiCl and DBU we obtained the (E)-9 and (Z)-9
isomers (71% yield, E/Z ) 2:3), both with the exo-
disposition on the bicyclo[3.2.0]heptane system. This fact
indicated the absence of (E)-selectivity of the reaction and
that the epimerization of the endo-aldehyde took place
in the presence of DBU. Any attempt to increase the (E)/
(Z) ratio was unsuccessful. The use of acetonitrile,
recommended in the original paper as solvent, furnished
lower yields and almost the same (E)/(Z) ratio.
The two isomers 9 were easily separated by flash
column chromatography. The DIBAH reduction of each
compound, performed at -70 °C, revealed that only the
(E)-isomer undergoes reduction and that, instead of the
corresponding lactol, the diol 10 is obtained in 84% yield.
In the same reaction conditions, as well as at higher
temperature, the (Z)-9 isomer was always recovered
unchanged. This fact makes it possible to perform the
reduction with DIBAH directly on the mixture of (E)-9
and (Z)-9, it being more convenient to isolate the diol 10
from the lactone (Z)-9 by flash column chromatography.
To minimize the drawback of the low yield of the
homologation, the latter could, in principle, be recycled
to the aldehyde 8 by an oxidative cleavage of the carbon-
carbon double bond. The synthesis was completed with
the selective MnO2 oxidation of the allylic hydroxy group
of 10 that furnished (82% yield) racemic raikovenal (1)
as an oil with the same physical chemical and spectro-
scopic properties recorded on the natural product and
reported in the literature.1
4-en d o-Meth ylbicyclo[3.2.0]h ep ta n -6-on e (4). Palladium
on carbon (10%, 1.82 g) was added to a solution of the bicyclic
ketone 3 (7 g, 57.4 mmol) in ethyl acetate (30 mL) at room
temperature. The reaction vessel was evacuated by aspirator
and thoroughly purged with hydrogen (three times), and the
resulting heterogeneous mixture was stirred under hydrogen at
3 atm. The reaction mixture was monitored by TLC analysis
(petroleum ether: dichloromethane 3:2) using vanillin reagent13
to test the progress of the reaction. After 3 h, the hydrogen was
evacuated, the catalyst filtered off on Celite, and the filtrate
concentrated under reduced pressure to give the crude product
4 (6.73 g, 95%) as a colorless oil. IR (liquid film): ν 2935, 2864,
1768 cm-1 1H NMR: δ 3.49-3.30 (m, 1H), 3.13 (ddd, J ) 4.8;
.
J ) 9.0; J ) 18.2, 1H), 2.92-2.73 (m, 1H), 2.50 (ddd, J ) 1.1; J
) 3.4; J ) 18.2, 1H), 2.21-2.02 (m, 2H), 2.01-1.73 (m, 2H),
1.51-1.30 (m, 1H),1.13 (d, J ) 6.8, 3H). 13C NMR: δ 213.8,
69.52, 60.79, 52.05, 39.71, 33.40, 29.84, 15.83. Anal. Calcd for
C8H12O: C, 77.37; H, 9.74. Found: C, 77.42; H, 9.79.
4-en d o-7,7-Tr im eth ylbicyclo[3.2.0]h ep ta n -6-on e (6). The
bismethylation of bicyclic ketone 4 was performed according to
the synthetic protocol previously described.3 A solution of
bicyclic ketone 4 (9.00 g, 72.5 mmol) dissolved in THF (50 mL)
was slowly added at room temperature to a suspension of NaH
(4.35 g, 182 mmol, 2.5 equiv) in THF (100 mL) containing MeI
(18.1 mL, 290 mmol, 4 equiv), and the mixture was stirred
overnight. During the first hour, the evolution of hydrogen was
observed and the increase in temperature to 40 °C was controlled
with a water bath. The color of the reaction mixture turned to
brown, and after 1 h a white product began to precipitate. The
reaction was monitored by GC and TLC (petroleum ether/diethyl
ether 9:1) as eluant. After 12 h, the reaction was stopped by
adding diethyl ether (250 mL) and water (50 mL). The organic
layer was washed with water (3 × 30 mL) and dried (Na2SO4).
The solvent was evaporated at ambient pressure, and the residue
was purified by distillation to give pure 6 (8.27 g, 75%) as a pale
yellow oil: bp (kugelrohr) ) 145 °C/15 mmHg. IR (liquid film):
ν 2954, 2866, 1764 cm-1 1H NMR: δ 3.54 (dd, J ) 1.1, J ) 7.6,
.
1H), 2.46 (dd, J ) 1.1, J ) 7.7, 1H), 2.18-1.92 (m, 1H), 1.91-
1.76 (m, 2H), 1.75-1.61 (m, 2H), 1.18 (s, 3H), 1.17 (d, J ) 6.7,
3H), 0.94 (s, 3H). 13C NMR: δ 221.2, 65.44, 59.03, 43.20, 38.83,
35.43, 28.20, 26.02, 15.61, 15.32. Anal. Calcd for C10H16O: C,
78.89; H, 10.59. Found: C, 78.93; H, 10.53.
P r epar ation of 4-en do-7,7-Tr im eth ylbicyclo[3.2.0]h eptan -
6-on e (6) by Hyd r ogen a tion of F ilifolon e (5). The title
compound 6 was prepared by hydrogenation of filifolone (5)
according to the typical procedure described before for the
hydrogenation of compound 3. Filifolone (7.0 g, 46.6 mmol) was
dissolved in ethyl acetate (30 mL), and palladium on carbon
(10%, 1.8 g) was added. The reaction with hydrogen was
performed at 3 atm and gave the pure ketone 6 (6.73 g, 95%).
All the spectroscopic data are in agreement with those reported
before.
Con clu sion
We have accomplished the first stereoselective total
synthesis of racemic raikovenal taking advantage from
a practical preparation of the mainframework of this
marine natural sesquiterpenoid: the bicyclo[3.2.0]heptane
structure. The availability of enantiomerically pure
forms of compound 3 as well as of filifolone (5) make this
procedure a formal EPC synthesis12 of both enantiomers
of raikovenal.
(9) Kelly, E. S. Alkene Synthesis. In Comprehensive Organic Syn-
thesis; Trost, B. M., Ed.; Schreiber, S. L., Volume Ed.; Pergamon:
Oxford, 1991; Vol 1; p 761.
(10) Blanchette, M. A.; Choy, W. C.; Davis, J . T.; Essenfeld, A. P.;
Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25,
2183.
(11) Bu¨chel, K.-H., Ro¨chling, Korte, F. Ann. Chem. 1965, 685, 10.
(12) Seebach, D.; Hungerbuhler, E. Syntheses of Enantiomerically
Pure Compound (EPC Syntheses). In Modern Synthetic Methods;
Scheffold, R., Ed.; Springer-Verlag: Berlin, 1980; p 91.
(E)- an d (Z)-6-(Meth oxym eth yliden e)-4-en do-7,7-tr im eth -
ylbicyclo[3.2.0]h ep ta n e (7). (Methoxymethyl)trimethylsilane
(6.1 mL, 39.5 mmol) in dry THF (30 mL) was cooled to -78 °C,
and sec-butyllithium (30.4 mL, 39.5 mmol, 1.3 M in hexanes)
was slowly added. The mixture was warmed at -25 °C and held
(13) Casey, M.; Leonard, J .; Lygo, B.; Procter, G. Advanced Practical
Organic Chemistry; Chapman and Hall: New York, 1990; p 114.

Notes
J . Org. Chem., Vol. 63, No. 7, 1998 2391
at this temperature for 1.5 h to complete formation of (methoxy-
(trimethylsilyl)methyl)lithium.8 The above pale yellow solution
was cooled to -35 °C, and the bicyclic ketone 6 (3.0 g, 19.70
mmol) was added. The mixture was slowly allowed to warm to
25 °C over 2 h, dry pyridine (4.7 mL, 60.0 mmol) was added,
the resulting mixture was cooled to 0 °C, and thionyl chloride
(2.9 mL, 39.5 mmol) dissolved in THF (10 mL) was slowly added.
The deep brown mixture was allowed to react at room temper-
ature and under magnetic stirring for 16 h, diethyl ether (150
mL) was added, and the mixture was quenched with saturated
aqueous ammonium chloride (2 × 20 mL), water (3 × 30 mL),
and saturated aqueous sodium chloride solution (2 × 20 mL),
dried (Na2SO4), and evaporated under reduced pressure to give
(1.69 g, 45%) a mixture of (E)- and (Z)-7 (E:Z ) 3:2) as an oil.
) 6.4, 3H). 13C NMR: δ 170.2(s), 146.7(d), 122.8(s), 65.48(t),
47.10(d), 46.37(d), 39.38(s), 38.65(d), 37.34(d), 34.47(t), 29.73(t),
27.58(q), 27.37(t), 24.36(q), 14.01(q). Anal. Calcd for C15H22O2:
C, 76.88; H, 9.46. Found: C, 76.80; H, 9.41. (E)-9: mp 99-101
°C; IR (KBr): ν 2948, 2862, 1745, 1660, 1185, 1023 cm-1
.
1H
NMR: δ 6.82 (td, J ) 2.8, J ) 10.4, 1H), 4.36 (t, J ) 7.5, 2H),
2.84 (tdd, J ) 2.5, J ) 2.5, J ) 7.4, 2H), 2.54 (m, 1H), 2.34-
2.17 (m, 2H), 1.98-1.17 (m, 5H), 1.09 (s, 3H), 0.90 (s, 3H), 0.85
(d, J ) 6.3). 13C NMR: δ 171.1 (s), 143.2 (d), 124.4 (s), 65.73
(t), 47.02 (d), 45.53 (d), 43.32 (d), 39.01 (s), 36.68 (d), 34.57 (t),
27.77 (q), 27.27 (t), 25.91 (t), 24.93 (q), 14.37 (q). Anal. Calcd
for C15H22O2: C, 76.88; H, 9.46. Found: C, 76.85; H, 9.40.
(1r,4â,5r,6r,E)-2-[(4,7,7-Tr im et h ylb icyclo[3.2.0]h ep t -6-
yl)m eth ylid en e]bu ta n e-1,4-d iol (10). A solution of DIBAH
(1 M, 5.5 mL, 5.5 mmol) in n-hexane diluted with dried diethyl
ether (20 mL) was added to a stirred solution of (E)-9 (0.260 g,
1.10 mmol) dissolved in diethyl ether (20 mL) at -70 °C.
Stirring was continued for 2 h. Then water was added, and the
stirred mixture was allowed to warm to 0 °C. A solution of HCl
(10%) was added until the aluminates were completely dissolved.
The organic phase was washed again with the HCl solution,
dried (Na2SO4), filtered, and concentrated under reduced pres-
sure to obtain the diol 10 (0.222 g, 84%) as a white solid: mp
1
Spectra were recorded on a sample of the isomeric mixture. H
NMR: δ 5.76 and 5.56 (two singlets, 1:3 ratio for (Z) and (E)
isomers, 3H), 3.47 and 3.45 (two singlets, 3:1 ratio for (E) and
(Z) isomers, 3H), 3.13 (dd, J ) 1.0, J ) 7.5, 1H), 2.21 (dd, J )
0.9, J ) 7.6, 1H), 1.97-1.31 (m, 5H), 1.20 and 1.17 (two singlets,
1:3 ratio for the (Z) and (E) isomers, 3H), 1.08 (s, 3H), 1.03 (d,
J ) 6.5, 3H). 13C NMR: (E)-isomer: δ 140.0, 126.7, 59.58, 47.48,
44.26, 40.02, 37.48, 34.33, 29.56, 27.81, 19.55, 15.04. (Z)-
isomer: δ 137.2, 127.6, 59.08, 48.11, 45.88, 41.43, 38.83, 34.98,
32.94, 27,62, 20,83, 16,38. Anal. Calcd for C12H20O: C, 79.94;
H, 11.18. Found: C, 80.01; H, 11.08.
66-68 °C. IR (KBr): ν 3430, 2944, 1283 cm-1 1H NMR: δ 5.55
.
(d, J ) 9.3, 1H), 4.02 (s, 2H), 3.88-3.65 (m, 2H), 2.47-2.25 (m,
3H), 2.14 (dd, J ) 0.8, J ) 7.5, 1H), 1.89-1.65 (m, 3H), 1.55-
4-en d o-7,7-Tr im et h ylb icyclo[3.2.0]h ep t a n e-6-ca r b a ld e-
h yd e (8). The mixture of enol ethers (E)- and (Z)-7 (1.10 g, 6.1
mmol) was stirred with 90% formic acid (10 mL) at room
temperature for 1 h. The mixture was poured into a saturated
aqueous sodium bicarbonate solution and extracted with ethyl
acetate (3 × 30 mL), dried (Na2SO4), and filtered. Evaporation
of the residue gave the aldehyde 8 (0.97 g, 96%) as a 4:1 mixture
of the exo and endo isomers at C6. IR (liquid film): ν 2947, 2862,
1.30 (m, 3H), 1.10 (s, 3H), 0.85 (s, 3H), 0.83 (d, J ) 4.7, 3H). 13
C
NMR: δ 135.8 (s), 133.7 (d), 68.68 (t), 62.40 (t), 46.61 (d), 46.24
(d), 39.62 (d), 37.51 (s), 36.76 (d), 34.38 (t), 32.84 (t), 27.02 (q),
26.92 (t), 23.95 (q), 14.00 (q). Anal. Calcd for C15H26O2: C,
75.58; H, 11.00. Found: C, 75.63; H, 10.85.
(1r,4â,5r,6r,E)-4-Hydr oxy-2-[(4,7,7-tr im eth ylbicyclo[3.2.0]-
h ep t-6-yl)m eth ylid en e]bu ta n a l (1, r a ik oven a l). The diol 10
(0.220 g, 0.92 mmol) was dissolved in dichloromethane (10 mL),
and the solution was cooled to 0 °C with an ice bath before
adding MnO2 (1.0 g) under magnetic stirring. After 2 h at 0 °C,
the temperature was allowed to rise at room temperature. The
progress of the reaction was monitored by TLC (petroleum ether/
diethyl ether 2:3) and was judged complete after 20 h. The
mixture was filtered on Celite, and the dichloromethane was
evaporated under reduced pressure to give pure raikovenal
(0.180 g, 82%) as an oil. IR (liquid film): ν 3414, 2950, 2865,
1707 cm-1 1H NMR: δ 10.8 and 9.78 (two d: d, J ) 6.0, endo
.
and d, J ) 1.8, exo, 1H), 3.00 (m, 1H), 2.69 and 2.49 (two dd:
dd, J ) 6.0, J ) 10.1, endo and dd, J ) 1.7, J ) 7.5, exo, 1H),
2.14 (dd, J ) 7.9, J ) 8.4, 1H), 1.97-1.41 (m, 6H), 1.14 (s, 3H),
1.06 (s, exo) and 1.04 (s, endo)(two singlets, 3H), 0.82 (d, J )
6.4, 3H). 13C NMR: exo isomer: δ 204.9, 53.32, 48.08, 47.42,
39.00, 36.54, 34.32, 27.44, 27.22, 24.68, 14.08; endo isomer: δ
206.3, 56.22, 48.08, 46.56, 38.68, 36.18, 34.56, 28.31, 27.22, 24.83,
14.56. Anal. Calcd for C11H18O: C, 79.46; H, 10.92. Found:
C, 79.38; H, 19.87.
1764, 1625, 1146 cm-1
.
1H NMR: δ 9.40 (s, 1H), 6.64 (d, J )
(1r,4â,5r,6r,E)- a n d (1r,4â,5r,6r,Z)-2-[(4,7,7-Tr im eth yl-
bicyclo[3.2.0]h ep t-6-yl)m eth ylid en e]bu tyr ola cton e (9). To
a suspension of LiCl (0.30 g, 7.0 mmol) in dry THF (25 mL),
stirred under nitrogen at room temperature, were added γ-bu-
tyrolactone-R-diethylphosphonate11 (1.54 g, (6.94 mmol), DBU
(0.66 g, 4.33 mmol), and finally the aldehyde 8 (0.48 g, 2.9 mmol).
The progress of the reaction was followed by TLC and judged
completed after 16 h. The reaction mixture was diluted with
diethyl ether (50 mL) and quenched with water (20 mL). The
usual workup provided compound 9 (0.480 g, 71%) as a mixture
of (E) and (Z) isomers (Z/E ) 1.5), separated by flash column
chromatography (petroleum ether/diethyl ether 4:1) to obtain the
two isomers as solids. (Z)-9: mp 84-86 °C; IR (KBr): ν 2930,
10.5, 1H), 3.60 (t, J ) 6.7, 2H), 2.64 (dd, J ) 6.6, J ) 10.4, 1H),
2.61-2.27 (m, 3H), 2.26-2.21 (dd, J ) 0.6, J ) 7.7, 1H), 1.90-
1.58 (m, 3H); 1.62-1.31 (m, 3H), 1.10 (s, 3H), 0.93 (s, 3H), 0.84
(d, J ) 6,5, 3H). 13C NMR: δ 196.1 (d), 159.8 (d), 139.6 (s), 61.79
(t), 46.75 (d), 45.69 (d), 41.11 (d), 38.91 (s), 36.76 (d), 34.20 (t),
28.29 (t), 27.21 (q), 26.91 (t), 24.08 (q), 13.84 (q). Anal. Calcd
for C15H24O2: C, 76.22; H, 10.24. Found: C, 76.12; H, 10.21.
Ack n ow led gm en t. This work was supported in part
by research grants from the Ministero dell’Universita`
e della Ricerca Scientifica (MURST), Italy, the Consiglio
Nazionale delle Ricerche (CNR), Italy, and by the
Universita` di Bologna (Progetto d’Ateneo: Biomodula-
tori organici).
2867, 1737, 1654, 1169, 1084, 1024 cm-1 1H NMR: δ 6.30 (td,
.
J ) 2.2, J ) 10.9, 1H), 4.29 (t, J ) 7.4, 2H), 3.77 (dd, J ) 7.0,
J ) 11.0, 1H), 2.91 (m, 2H), 2.37 (q, J ) 6.7, 1H), 2.18 (t, J )
7.7, 1H), 1.95-1.29 (m, 5H), 1.06 (s, 3H), 0.90 (s, 3H), 0.87 (d, J
J O972098E