Synthesis and structural characterisation of ring B oxidised derivatives of dehydroabietic acid

Article abstract of DOI:10.1039/b103737b

The synthesis and structural characterisation of some new derivatives of dehydroabietic acid, oxidised in the 6 and 7 positions of ring B, are described. Other known derivatives were exhaustively characterised for the first time and the previous NMR assig

Full text of DOI:10.1039/b103737b

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Synthesis and structural characterisation of ring B oxidised
derivatives of dehydroabietic acid
Silvia M. C. S. Monteiro,a Armando J. D. Silvestre,a Artur M. S. Silva,a Jose A. S. Cavaleiro,*a
Vitor Felixa and Michael G. B. Drewb
a Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
E-mail: jcavaleiro=dq.ua.pt; Fax: ]351 234 370 084
b Department of Chemistry, University of Reading, W hiteknights, Reading, UK RG6 6AD,
Received (in Montpellier, France) 25th April 2001, Accepted 28th May 2001
First published as an Advance Article on the web 17th July 2001
The synthesis and structural characterisation of some new derivatives of dehydroabietic acid, oxidised in the 6 and
7 positions of ring B, are described. Other known derivatives were exhaustively characterised for the Ðrst time and
the previous NMR assignments for three compounds are corrected.
Dehydroabietic acid (1a) can be easily obtained by catalytic
dehydrogenation of abietic type resin acids, which are very
Results and discussion
abundant in pine resin.1 This acid has been considered as an
interesting starting material for the synthesis of new com-
pounds with interesting biological properties.2 In particular,
some oxygenated derivatives of dehydroabietic acid have
demonstrated promising antifungal3 and tumour-inhibitory4
properties.
Synthesis
Methyl dehydroabietate (1b) was prepared as described in the
literature;1 it was then treated with chromium trioxide to give
compound 2 in 67% yield, as well as minor amounts of methyl
13-acetyl-7-oxopodocarpe-8,11,13-trien-15-oate, 3, and methyl
13-(1-acetoxy-1-methylethyl)-7-oxopodocarpe-8,11,13-trien-15-
oate, 4 (Scheme 1). These three compounds are known from
the literature,7,8 however, they have not been characterised by
13C NMR, and some of their reported 1H NMR assignments
were considered to be incorrect. The 13C NMR data, and the
new 1H NMR assignments are reported below.
The ketone 2 was then reduced with sodium borohydride in
methanol to obtain a diastereomeric mixture of two alcohols 5
(Scheme 2). This mixture could not be separated by pre-
parative TLC; however the NMR analysis allowed us to con-
clude that it was composed of a 1 : 10 ratio of these two
alcohols. The mixture was then treated with mesyl chloride in
dry triethylamine9 to yield 6, a compound that has already
been prepared from 1b following a di†erent synthetic route.10
Our target compound, methyl 2-formyl-3-(2-formyl-4-iso-
propylphenyl)-1,3-dimethylcyclohexanecarboxylate, 7, was
then prepared by treating compound 6 with sodium periodate
in the presence of catalytic amounts of osmium tetroxide.11 In
addition to 7, other oxidised derivatives 8È11, and the lactone
12, were also isolated (Scheme 3). Compound 8 is probably
the oxidation product of the 2-CHO group of compound 7,
while compounds 9È11 represent di†erent degrees of oxidation
of compound 6 with an uncleaved C ÈC bond. The forma-
Pursuing our studies in the chemical transformation of
dehydroabietic acid,5,6 we have been looking at the possibility
of preparing new compounds from 1b through the cleavage or
functionalisation of ring B. Oxidative cleavage of the C ÈC
6
7
bond of 1 can be a way to prepare the aldehyde or carboxylic
acid derivatives (7 and 8) that could then be used in the syn-
thesis of other compounds with potential biological interest.
During the synthetic studies of oxidative cleavage of the
C ÈC bond, several new dehydroabietic acid derivatives
6
7
(7È10) were prepared and fully characterised by MS and NMR
techniques. Various known compounds were also obtained; in
some cases (11 and 12) they were fully characterised by MS
and NMR for the Ðrst time; for others (2È4) the published 1H
NMR assignments were corrected and the 13C NMR data
reported for the Ðrst time.
6
7
Scheme 1 Oxidation of methyl dehydroabietate (1b) with CrO .
3
DOI: 10.1039/b103737b
New J. Chem., 2001, 25, 1091È1097
1091
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001

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The assignment of the quaternary carbons C-8, C-9 and
C-13 was performed using a one-dimensional selective INEPT
experiment carried out with compound 2. Table 1 shows the
connectivities found and the corresponding 13C resonance
assignments upon irradiation of H-11 (d 7.30) and 13-
CH(CH ) (d 2.90). No signal enhancement was observed for
3 2
the resonance at d 152.9, which was then assigned to C-9. The
resonances of such quaternary carbons in compounds 3 and 4
were assigned by comparison with data obtained for com-
pound 2.
In the 1H NMR spectrum of compound 5 two signals in a
1 : 10 ratio, at d 4.72 and 4.85, can be detected; these chemical
shifts are characteristic of benzilic protons with a geminal
hydroxyl group, and were therefore attributed to H-7. The
major signal appears as a doublet of doublets and has been
assigned to the H-7a proton, while the minor signal appears
as a triplet and was assigned as H-7b; these data indicate that
alcohol 5b was formed predominantly rather than its stereoi-
somer 5a.
Scheme
2
Synthesis of methyl 13-isopropylpodocarpe-6,8,11,13-
tetraen-15-oate, 6.
Compound 6 was characterised by NMR and MS, and the
obtained spectroscopic results are in agreement with the liter-
ature data.10
tion of the lactone 12 can result from the oxidation of com-
pound 9 to form a 6,7-dione derivative; the enolic form of this
dione might lactonise spontaneously to yield 12. Alternatively,
the former enol might also result from the hydroxylation of
the b,c-unsaturated ester 11, catalysed by osmium tetroxide.12
Compounds 7È10 are reported for the Ðrst time, while com-
pounds 11 and 12 have already been described13 without con-
sidering any spectroscopic characterisation.
Formation of compounds 7 and 8 resulted from the oxida-
tive cleavage of the ring B of 6, so they are structurally di†er-
ent from the other derivatives characterised so far in this
paper, therefore some di†erences in the NMR proÐles were
observed. For compound 7, the 1-CO CH proton resonance
2
3
appears at d 3.00; this shift to lower d values, as well as the
shift to higher d values of H-2 (d 3.90), when compared to
those of the preceding compounds, is probably due to the
anisotropic shielding e†ect of the carbonylic group in position
2. The resonances at d 10.77 and 9.98 are characteristic of
CHO protons: the signal at d 10.77 was assigned to 2-CHO,
since it appears as a doublet (J 4.2 Hz) by coupling with H-2;
the resonance at d 9.98 was then assigned to 2@-CHO. Assign-
ment of the quaternary carbons C-1@, C-2@ and C-4@ of com-
pound 7 was performed by using HMBC experiments (Fig. 1):
correlations were observed between the H-6@ resonance (d
7.42) and the carbon resonances at d 135.8 and 147.4, assigned
to C-2@ and C-4@, respectively. Assignment of C-2@ was further
conÐrmed since correlation was observed with the proton
resonance at d 9.98 (2@-CHO). The C-1@ resonance was assigned
Structural characterisation
The general features of the 1H and 13C NMR of methyl de-
hydroabietate and some derivatives are well described in the
literature,6 allowing us to directly assign several resonances of
the synthesised compounds.
Analysis of the NMR spectra (1H, 13C HETCOR, COSY
and selective INEPT) of compounds 2È4 allowed us to con-
clude that the literature assignments8 of the resonances of H-5
and H-6 were incorrect.
The methinic C-5 and the methylenic C-6 carbons were
unambiguously assigned, respectively at d 43.3È43.6 and 37.7È
38.0 using DEPT experiments. The assignments of the H-5
and H-6 resonances were made by an analysis of the
HETCOR spectra. The resonances of the two H-6 protons
appear at d 2.28È2.40 (overlapped with the resonance of H-1)
and at d 2.71È2.74 (overlapped with the resonance of H-5),
these assignments were conÐrmed with the COSY spectrum.
On the other hand, coupling was also observed between the
resonance at d 2.28È2.40, assigned to one H-1 proton and that
at d 1.61È1.82; this in conjugation with the correlation of these
two proton resonances and the carbon resonance at d 37.0È
38.0 conÐrmed their assignments to H-1 and C-1.
Table 1 Signal enhancements observed by irradiation of the H-11
and 13-CH(CH ) resonances of compound 2
3 2
1H irradiation (d)
13C signal enhancements (d)
13-CH(CH ) (2.90)
C-13 (146.8); C-12 (132.5); C-14 (124.9);
3 2
13-CH(CH ) (23.7 and 23.6)
3 2
H-11 (7.30)
C-13 (146.8); C-8 (130.5)
Scheme 3 Oxidative cleavage of 6 with NaIO catalysed by OsO .
4
4
1092
New J. Chem., 2001, 25, 1091È1097

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Fig. 1 Connectivities found in the HMBC spectrum of 7.
Fig. 2 Connectivities found in the HMBC spectra of 10 and 11.
at d 144.7 since correlations with the proton resonances of
H-5@, H-3@ and 3-CH (d 7.36, 7.82 and 1.14, respectively) were
the appearance of a new signal at d 6.14, suggested that com-
pound 11 di†ers from 2 by the presence of a double bond
between carbon centres C-5 and C-6. The resonances of 13-
CH(CH ) , as well as those of 13-CH(CH ) , appear at d
3
observed. Assignments of the resonances of 1-CH and 3-CH
3
3
(d 1.48 and 1.14, respectively) were also conÐrmed through the
correlations observed in the HMBC spectrum.
3 2
3 2
Assignment of most of the 1H and 13C resonances of com-
pound 8 was made by comparison with the results obtained
for compound 7. The resonance of the carbonylic proton
2-CHO observed in compound 7 was not found for 8. On the
other hand, in the mass spectrum of compound 8 it has been
possible to observe a molecular ion at m/z 360, and two
intense fragments at m/z 147 and 213, resulting from cleavage
of the molecule at the C ÈC bond, giving a fragment at m/z
values di†erent from the usual ones. According to previously
published work6 this might be due to steric hindrance caused
by substituents in positions 12 or 14; however, taking into
consideration the above-mentioned molecular ion no aro-
matic substituents were expected. In addition, in the aromatic
region of the 1H spectrum three signals were detected; H-14
appears as a singlet at d 7.98 while H-11,12 appear as an AB
system at d 7.44 and 7.45.
2
1{
213 corresponding to the aliphatic part of the molecule, and a
fragment at m/z 147 corresponding to the aromatic part. The
fragment with m/z 147 is also observed in the mass spectrum
of compound 7, suggesting that no structural modiÐcations
occurred in the aromatic part of 8. Instead of the fragment at
m/z 213 observed for 8 compound 7 shows a fragment at m/z
197; suggesting that compound 8 has one more oxygen atom
in the aliphatic part. These observations are consistent with
the replacement of the 2-CHO group of compound 7 by a
carboxylic group in compound 8.
Assignment of all proton and carbon resonances was made
by considering 2D-NMR (HETCOR and HMBC) and DEPT
experiments. Based on the connectivities found in the HMBC
spectrum (Fig. 2) and starting from the 13-CH(CH ) reso-
3 2
nance, 13-CH(CH ) , C-14, C-12 and C-13 resonances were
3 2
assigned. The HETCOR spectrum allowed the assignment of
H-14 and H-12 resonances, and also the conÐrmation of those
of 13-CH(CH ) . Starting from H-14, the connectivities found
3 2
in the HMBC spectrum allowed us to identify the resonances
of C-9, C-12 and C-7. The connectivities with the resonance of
H-6 (d 6.14) allowed us to unambiguously assign the reso-
nances of C-10 and C-4. The assignment of the quaternary
C-5 resonance at d 167.4 was further conÐrmed by its absence
in the DEPT spectrum. Finally, the resonances of H-11 and
H-12 have very close chemical shifts, and it has not been pos-
sible to di†erentiate them based on the HETCOR spectrum.
Compound 12 is known from the literature, although it has
not yet been fully characterised.13 The 1H spectrum of com-
pound 12 conÐrmed that H-5 and vinylic H-6 protons are not
present. This indicates that, in addition to the C ÈC double
To conÐrm this hypothesis, a small amount of compound 8
was treated with diazomethane. The 1H NMR of the resulting
product revealed the presence of an additional singlet at d
3.77, characteristic of a methyl ester proton resonance, con-
Ðrming the presence of an extra carboxylic group in com-
pound 8.
The NMR characterisation of 9 was achieved by compari-
son with the spectroscopic data of the previously character-
ised compounds and also with HETCOR experiments. The
H-5 resonance appears as a doublet at d 2.91 due to coupling
with H-6, which appears as a doublet of doublets at d 4.47 due
to coupling with H-5 and 6-OH, this last proton resonance
appears as a doublet at d 3.47. It was also possible to observe
a shift to higher d values in the resonance of H-16 and H-17 to
d 1.53 and 1.40, respectively, relative to the previously charac-
terised compounds. The assignment of quaternary carbons
C-9 and C-13 was performed using a one-dimensional selec-
tive INEPT experiment, by irradiation of H-12 and H-14.
Upon irradiation, enhancements were found in the signal at d
153.1, which was therefore assigned to C-9. The resonance of
C-13 was then assigned at d 147.4.
The 1H and 13C resonances of compound 10 were assigned
by taking into account the characterisation of compound 9.
The assignment of the resonances of protonated carbons was
conÐrmed through DEPT and HETCOR experiments, which
also allowed the assignment of the H-1 (d 2.14 and 2.38), H-2
(d 1.88) and H-3 (d 1.64) resonances. The resonances of quat-
ernary carbons and the 5-OH proton were assigned through
an HMBC experiment. The main connectivities observed are
shown in Fig. 2.
Compound 11 has already been described in the liter-
ature,13 however its characterisation by NMR and MS has
not yet been reported. The molecular ion at m/z 326, two mass
units less than that of compound 2, as well as the disap-
pearance of the resonances corresponding to H-5 and H-6 and
5
6
bond, another group replaces H-6. The disappearance of the
C-6 resonance, as observed for compound 11, and the appear-
ance of a new carbon resonance at d 142.4 strongly suggested
that C-6 exists in an enolic form. Finally, no proton resonance
for a COOCH group was observed, and the mass spectrum
3
for this compound showed a mass fragment of m/z 310. All
this information coupled with a single crystal X-ray di†raction
analysis allowed the identiÐcation of the molecular structure
of this compound as the lactone shown in 12.
The molecular structure found by X-ray di†raction for com-
pound 12 is shown in Fig. 3, together with the atomic label-
ling scheme adopted. The distance between the carbon atom
C6 and the oxygen atom O152 is 1.403(5) A, indicating deÐni-
tively the formation of a Ðve-membered lactone ring. The mol-
ecule has a planar central core constituted of the aromatic and
lactone rings and the intervening six-membered ring. In fact,
the maximum deviation from the least-squares plane deter-
mined by the thirteen atoms that compose this central core is
0.140(4) A for carbon atom C5. Despite this planarity, the
bonds C5ÈC6 [1.321(6) A] and C7ÈO71 [1.241(6) A] both
have double bond character, indicating that they are not
involved in p electronic delocalisation. Furthermore the dis-
tances C7ÈC8 [1.491(6) A], C7ÈC6 [1.457(7) A] and C6ÈO152
[1.403(5) A] are typical of single bond lengths. The distance
C15ÈO151 [1.403(5) A] is shorter than the distance C7ÈO71
New J. Chem., 2001, 25, 1091È1097
1093

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Fig. 4 Connectivities found in the HMBC spectrum of 12.
that extensive fragmentation of compound 9 occurred under
EI conditions. For compound 10 the molecular ion is not
observed in the EI mass spectrum; however, the fragment
[M ] H]~` can be observed under FAB` conditions. In the
EIÈMS spectrum of compound 10, the highest mass observed
was at m/z 330, corresponding to the fragment [M [ CO]~`,
the most relevant fragments correspond to the loss, from the
previous fragment, of 10-CH (m/z 315) followed by the loss of
Fig. 3 ORTEP view of 12 with thermal ellipsoids drawn at 30%
probability level. Selected bond distances (A) and angles (¡): C7ÈO71
1.241(6), C7ÈC8 1.491(6), C6ÈC7 1.457(7), C5ÈC6 1.321(6), C6ÈO152
1.403(5), O152ÈC15, 1.380(6), C15ÈO151, 1.200(6), C15ÈC4 1.526(6),
C4ÈC5 1.520(6); C5ÈC6ÈO152 114.0(4), O152ÈC15ÈC4 110.3(4), C4È
C5ÈC6 108.6(3), C5ÈC4ÈC15 100.3(4), C15ÈO152ÈC6 106.6(3).
3
HCO CH (m/z 255) and the loss of CO CH (m/z 271). The
2
3
2
3
main fragments observed in MS spectra of 12 result from the
cleavage of the lactone ring. These fragments corresponded to
[M [ 44]~` [loss of C(O)O], [M [ 28]~` (loss of CO) and
[M [ 59]` [loss of C(O)O and CH ].
In conclusion, it can be stated that the present work is
3
related to a valorisation procedure of resin acids; it describes
the syntheses and characterisation of several new dehydroa-
bietic acid derivatives, which arise from the cleavage or func-
tionalisation of ring B of such a resin acid.
by ca. 0.04 A, suggesting that the carbonyl bond of the ester
group also retains some double bond character. So the unique
p electronic delocalisation present is this compound is due to
the aromatic stabilisation of the benzene ring.
The absolute conÐguration of an organic compound cannot
always be obtained directly and unequivocally from an X-ray
structure determination, even if an appropriate X-ray radi-
ation source is used. The X-ray data for compound 12 were
collected with molybdenum radiation and therefore its absol-
ute stereochemistry was not determined. However, the R con-
Ðguration of the two chiral centres C10 and C4 is known from
the precursor compound 1b and the molecular diagram shown
in Fig. 3 corresponds to the correct structure. Thus, the
methyl groups attached to the carbon atoms C4 and C10 are
above the least-squares plane mentioned above by 1.169(6)
(C17) and 0.932(2) A (C16) while the carbon atoms C1 and C3
are below it by 1.371(6) and 1.520(6) A, respectively. The
hexane ring adopts an approximate chair conformation with
the following puckering parameters: Q 0.550(5) A, h 7.9(5)¡, /
91(4)¡.14
Experimental
General
NMR spectra were acquired on a Bruker AMX 300 spectro-
meter (300.13 and 75.47 MHz, for 1H and 13C, respectively)
using CDCl as solvent, TMS as internal reference; chemical
3
shifts (d) in ppm and coupling constants (J) in Hz. 1HÈ1H
coupling constants are reported as calculated from spectra
and, as a result, slight di†erences between J and J were
ab
ba
occasionally obtained. Unequivocal 1H and 13C assignments
were made with the aid of 2D-HETCOR (1H/13C) experi-
ments, one-dimensional selective INEPT16 (long-range C/H
coupling constants optimised to 7 Hz) and HMBC (the low-
pass J-Ðlter portion of the experiment was optimised for an
average of one-bond heteronuclear coupling of 145 Hz. The
delay for evolution of long-range couplings was optimised for
7 Hz). Electron impact (EI, 70 eV), fast atomic bombardment
(FAB)` using 3-nitrobenzyl alcohol as matrix, and high
resolution (HRMS) mass spectra were obtained with VG
Autospec Q and M mass spectrometers. Preparative thin-layer
Finally, in the crystal structure the molecules of 12 are self-
assembled only by crystal packing forces. No hydrogen bonds
were found and no relevant structural order is apparent from
the crystal packing.
Having the X-ray structural proof in hand, it was possible
to complete the NMR analysis. Assignment of the resonances
of quaternary carbons C-5, C-7, C-8, C-9, C-13 and C-15 was
made by considering the connectivities found in the HMBC
spectrum (Fig. 4); the resonance at d 142.4 was assigned by
default to C-6.
chromatography was done using Riedel silica gel 60 DGF
.
254
Column chromatography used Merck silica gel 60, 70È230
mesh. All chemicals and solvents were obtained from com-
mercial sources and used as received or dried according to
standard procedures.
A general interpretation of the electron impact (EI) mass
spectra of all synthesised compounds can be based on the
characteristic fragmentations of methyl dehydroabietate 1b,15
and of the functional groups present. Fragments such as
M~`, [M [ CH ]`, [M [ COOCH ]` and [M [ (CH
Table 2 Relative intensity (%) of fragments found in the mass spectra
of compounds 2È4, 6 and 9
3
3
3
Fragment
2
3
4
6
9
] HCO CH )]`, which are typical for 1b, can be found in the
2
3
mass spectra of compounds 2, 3, 4, 6 and 9 as the most rele-
vant fragments (Table 2). The main fragments observed the in
mass spectra of compounds 7 and 8 result from cleavage of
the C ÈC and C ÈC bonds, respectively. The mass spec-
trum of compound 9 was characterised by a cluster of peaks
in a small range of m/z values; this kind of spectrum indicates
[M]~`
78
19
36
83
44
47
31
68
13
22
93
32
90
71
[M [ CH ]`
a
3
[M [ CO CH ]`
22
100
2
3
[M [ CO CH ] CH ]~`
100
100
100
2
3
3
3
1{
2
1{
a Not observed.
1094
New J. Chem., 2001, 25, 1091È1097

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Syntheses
Methyl 7-hydroxy-13-isopropylpodocarpe-8,11,13-trien-15-
oate, 5. To a solution of 2 (240 mg, 0,74 mmol) in methanol
Methyl 13-isopropylpodocarpe-8,11,13-trien-15-oate (methyl
dehydroabietate), 1b. Methyl dehydroabietate was obtained by
catalytic dehydrogenation of methylated resin according to
known methods.1
(25 ml) under nitrogen at 0 ¡C, NaBH (225 mg, 5.92 mmol)
4
was slowly added. After stirring for 3 h, the solvent was
removed by evaporation. The residue was dissolved in chloro-
form, poured into water and acidiÐed with commercial hydro-
chloric acid (pH of resulting mixture adjusted to 2). The
mixture was extracted with chloroform (3 ] 50 ml), the com-
bined organic layers were dried over anhydrous sodium
sulfate, and the solvent was evaporated. The residue was dis-
solved in dichloromethane (2 ml) and puriÐed by thin layer
chromatography using light petroleumÈethyl acetate (4 : 1) as
eluent. Methyl 7-hydroxy-13-isopropylpodocarpe-8,11,13-
trien-15-oate 5 (198 mg, 81%), was isolated as a mixture of
diastereomers. Yellow oil; d (300.13 MHz; CDCl ; Me Si)
Oxidation of methyl dehydroabietate 1b. A solution of CrO
(165 mg, 1.65 mmol) in 9 ml of acetic anhydrideÈacetic acid
3
(2 : 1) was added dropwise to a solution of methyl dehydro-
abietate 1 (500 mg, 1.56 mmol) in acetic acid. The mixture was
stirred at room temperature for 15 min, heated at 50 ¡C with
magnetic stirring for 12 h. The mixture was then poured into
water and ice, extracted with chloroform (3 ] 100 ml), the
combined organic layers dried over anhydrous sodium sulfate,
and the solvent evaporated. The residue was dissolved in
dichloromethane (5 ml) and puriÐed by thin layer chromato-
graphy using light petroleumÈethyl acetate (4 : 1) as eluent.
After elution three spots were isolated; the higher one was
identiÐed as compound 2 (343 mg, 67%), the middle one as
compound 4 (36 mg, 6%) and the lower one as compound 3
(20 mg, 4%).
H
3
4
1.23 [6 H, d, J 6.9, 13-CH(CH ) ], 1.27 (3 H, s, H-17), 1.28 (3
3 2
H, s, H-16), 1.36È1.86 (6 H, m, H-1,2,3,6), 2.06 (1 H, d, J 7.2,
H-5), 2.21È2.31 (2 H, m, H-1,6), 2.87 [1 H, heptet, J 6.9, 13-
CH(CH ) ], 3.66 (s, 3 H, 15-OCH ), 4.72 (0.1 H, t, J 4.6, H-7b)
3 2
3
, 4.85 (1 H, dd, J 8.2 and 16.2, H-7a), 7.09 (1 H, dd, J 1.9 and
8.2, H-12), 7.16 (1 H, d, J 8.1, H-11), 7.38 (1 H, d, J 1.8, H-14);
d
(75.47 MHz; CDCl ; Me Si) 16.4 (C-16), 18.3 (C-2), 23.8
C
3
4
and 24.0 [13-CH(CH ) ], 25.4 (C-17), 32.7 [13-CH(CH ) ],
3 2
3 2
Methyl 13-isopropyl-7-oxopodocarpe-8,11,13-trien-15-oate,
33.6 (C-3), 36.4 (C-1), 37.5 (C-10), 37.8 (C-6), 43.3 (C-5), 47.2
2. Yellow oil; d (300.13 MHz; CDCl ; Me Si) 1.25 [6 H, d, J
(C-4), 52.0 (15-OCH ), 70.6 (C-7), 124.1 (C-11), 125.2 (C-14),
H
3 2
3
4
3
7.2, 13-CH(CH ) ], 1.26 (3 H, s, H-17), 1.34 (3 H, s, H-16),
125.8 (C-12), 137.5 (C-8), 146.4 (C-13), 146.6 (C-9), 178.7 (C-15);
1.61È1.82 (5 H, m, H-1,2,3), 2.28È2.40 (2 H, m, H-1,6), 2.71È
m/z (EI) 330 (M~`, 31%), 312 (25), 287 (9), 255 (20), 237 (100),
2.74 (2 H, m, H-5,6), 2.90 [1 H, heptet, J 6.9, 13-CH(CH ) ],
195 (26), 162 (37).
3 2
3.64 (3 H, s, 15-OCH ), 7.30 (1 H, d, J 8.1, H-11), 7.41 (1 H,
3
dd, J 8.4 and 2.2, H-12), 7.87 (1 H, d, J 2.4, H-14); d (75.47
Methyl 13-isopropylpodocarpe-6,8,11,13-tetraen-15-oate, 6.
To a solution of the diastereomeric mixture of 5 (198 mg, 0.60
mmol) in chloroform (10 ml) under nitrogen and at 0 ¡C, dry
triethylamine (330 ll, 2.40 mmol) and mesyl chloride (66 ll,
0.80 mmol) were added. After stirring for 3 h, the mixture was
poured into water. This mixture was extracted with chloro-
form (3 ] 30 ml), the combined organic layers were dried with
anhydrous sodium sulfate, and the solvent was evaporated to
dryness. The residue was dissolved in dichloromethane (2 ml)
and puriÐed by thin layer chromatography using light
petroleumÈethyl acetate (9 : 1) as eluent to give compound 6
(168 mg, 90%). Yellow oil; d (300.13 MHz; CDCl ; Me Si)
C
MHz; CDCl ; Me Si) 16.2 (C-16), 18.0 (C-2), 23.6 [13-
CH(CH ) ], 23.7 (C-17), 33.5 [13-CH(CH ) ], 36.9 (C-3), 37.0
(C-1), 37.2 (C-10), 37.7 (C-6), 43.6 (C-5), 46.5 (C-4), 52.1 (15-
3
4
3 2
3 2
OCH ), 123.4 (C-11), 124.9 (C-14), 130.5 (C-8), 132.5 (C-12),
3
146.8 (C-13), 152.9 (C-9), 177.7 (C-15), 198.4 (C-7); m/z (EI) 328
(M~`, 78%), 312 (19), 296 (16), 269 (36), 253 (100), 237 (13), 227
(12), 213 (29), 199 (20), 187 (37), 171 (15), 159 (19), 145 (15), 128
(20), 115 (23), 91 (16), 83 (18), 77 (13), 69 (15), 59 (41), 55 (23),
53 (13).
Methyl 13-acetyl-7-oxopodocarpe-8,11,13-trien-15-oate, 3.
H
3
3 2
4
Yellow oil; d (300.13 MHz; CDCl ; Me Si) 1.29 (3 H, s,
1.07 (3 H, s, H-17), 1.23 [6 H, d, J 6.9, 13-CH(CH ) ], 1.39 (3
H, s, H-16), 1.60È1.84 (5 H, m, H-1,2,3), 2.17 [1 H, d, J 11.4,
H
3
4
H-17), 1.36 (3 H, s, H-16), 1.76È1.85 (5 H, m, H-1,2,3), 2.39È
2.44 (2 H, m, H-1,6), 2.64 (3 H, s, 13-COCH ), 2.74È2.78 (2 H,
H-1], 2.85 [1 H, heptet, J 6.9, 13-CH(CH ) ], 2.92 (1 H, m,
3
m, H-5,6), 3.68 (3 H, s, 15-OCH ), 7.51 (1 H, d, J 8.4, H-11),
3
3 2
H-5), 3.64 (3 H, s, 15-OCH ), 5.71 (1 H, dd, J 9.3 and 2.7, H-6),
3
8.16 (1 H, dd, J 1.8 and 8.4, H-12), 8.55 (1 H, d, J 2.1, H-14);
6.51 (1 H, dd, J 9.45 and 3.15, H-7), 6.91 (1 H, d, J 1.2, H-14),
d
(75.47 MHz; CDCl ; Me Si) 16.4 (C-16), 18.0 (C-2), 23.4
7.06 (1 H, dd, J 8.1 and 1.8, H-12), 7.09 (1 H, d, J 8.1, H-11);
C
3
4
(C-17), 26.7 (13-COCH ), 36.4 (C-3), 36.8 (C-1), 37.6 (C-10),
d (75.47 MHz; CDCl ; Me Si) 17.9 (C-16), 18.4 (C-2), 20.8
3
C
3
4
38.0 (C-6), 43.3 (C-5), 46.6 (C-4), 52.3 (15-OCH ), 124.2 (C-11),
128.1 (C-14), 130.8 (C-8), 133.0 (C-12), 135.3 (C-13), 159.8 (C-9),
177.6 (C-15), 197.3 and 197.5 (C-7 and 13-COCH ); m/z (EI)
328 (M~`, 83%), 313 (44), 296 (25), 268 (48), 253 (100), 239 (11),
225 (15), 213 (47), 202 (32), 199 (33), 187 (66), 171 (16), 165 (13),
157 (12), 152 (11), 141 (18), 128 (30), 115 (31), 101 (14), 95 (19),
91 (13), 77 (13), 69 (18), 59 (25), 55 (22).
(C-17), 24.0 [13-CH(CH ) ], 33.5 [13-CH(CH ) ], 35.3 (C-1),
3
3 2
3 2
35.6 (C-3), 37.1 (C-10), 46.3 (C-5), 46.6 (C-4), 52.0 (15-OCH ),
121.6 (C-11), 124.6 (C-14), 125.7 (C-12), 129.8 (C-6), 128.3 (C-7),
3
3
132.5 (C-13), 145.0 (C-9), 146.3 (C-8), 178.5 (C-15); m/z (EI) 312
(M~`, 68), 297 (13), 253 (22), 237 (100), 223 (11), 212 (16), 209
(23), 197 (53), 183 (24), 179 (26), 167 (31), 165 (30), 155 (31), 147
(11), 141 (29), 128 (11), 115 (11), 59 (11).
Methyl 13-(1-acetoxy-1-methylethyl)-7-oxopodocarpe-
Oxidative cleavage of 6. To a solution of 6 (160 mg, 0.513
8,11,13-trien-15-oate, 4. Yellow oil; d (300.13 MHz; CDCl ;
mmol) in THF (15 ml) at 0 ¡C, OsO (1 mg) and pyridine (82
H
3
4
Me Si) 1.26 (3 H, s, H-17), 1.34 (3 H, s, H-16), 1.76È1.82 (5 H,
ll, 1.026 mmol) were added. The reaction mixture was stirred
4
m, H-1,2,3), 1.76 [6 H, s, 1@-(CH ) ], 2.04 (3 H, s, 1@-OCOCH ),
for 20 min and then an aqueous (10 ml) of solution NaIO
(549 mg, 2.565 mmol) was slowly added. After stirring for 23 h,
3 2
3
4
2.33È2.36 (2 H, m, H-1,6), 2.70È2.74 (2 H, m, H-5,6), 3.66 (3 H,
s, 15-OCH ), 7.34 (1 H, d, J 8.4, H-11), 7.53 (1 H, dd, J 2.4 and
the solution was poured into water. This mixture was
extracted with chloroform (3 ] 50 ml), the combined organic
layers were dried over anhydrous sodium sulfate, and the
solvent was evaporated to dryness. The residue was dissolved
in dichloromethane (3 ml) and puriÐed by thin layer chroma-
tography using dichloromethane as eluent. After several elu-
tions six spots were isolated; the higher one was identiÐed as
compound 10 (18 mg, 10%), the second as compound 7 (21
mg, 12%), the third as compound 12 (14 mg, 9%), the fourth
3
8.4, H-12), 7.98 (1 H, d, J 2.1, H-14); d (75.47 MHz; CDCl ;
C
3
Me Si) 16.4 (C-16), 18.1 (C-2), 22.3 (1@-OCOCH ), 23.6 (C-17),
4
3
28.5 [1@-(CH ) ], 36.4 (C-3), 37.0 (C-1), 37.3 (C-10), 37.8 (C-6),
3 2
43.5 (C-5), 46.6 (C-4), 52.2 (15-OCH ), 81.0 (C-1@), 123.2 (C-14),
3
123.6 (C-11), 130.1 (C-12), 130.6 (C-8), 144.1 (C-13), 153.8 (C-9),
168.8 (1@-OCOCH ), 177.8 (C-15), 198.2 (C-7); m/z (EI) 386
3
(M~`, 31%), 343 (68), 327 (100), 311 (50), 267 (19), 251 (66), 245
(20), 211 (16), 199 (15), 185 (16), 159 (19), 55 (11).
New J. Chem., 2001, 25, 1091È1097
1095

View Article Online
as compound 11 (10 mg, 6%), the Ðfth as compound 9 (32 mg,
18%), and the lower one as compound 8 (4 mg, 2%).
1.27 [6 H, d, J 6.9, 13-CH(CH ) ], 1.34 (3 H, s, H-17), 1.61È
1.68 (2 H, m, H-3), 1.71 (3 H, s, H-16), 1.82È1.96 (2 H, m, H-2),
3 2
2.09È2.18 (1 H, m, H-1), 2.38 (1 H, m, H-1), 2.96 [1 H, heptet,
J 6.9, 13-CH(CH ) ], 3.77 (3 H, s, 15-OCH ), 6.79 (1 H, s,
Methyl 2-formyl-3-(2-formyl-4-isopropylphenyl)-1,3-
dimethylcyclohexane carboxylate, 7. Yellow oil; d (300.13
3 2
3
5-OH), 7.31 (1 H, d, J 8.1, H-11), 7.51 (1 H, dd, J 2.1 and 8.1,
H-12), 7.96 (1 H, d, J 2.1, H-14); d (75.47 MHz; CDCl ;
H
MHz; CDCl ; Me Si) 1.14 (3 H, s, 1-CH ), 1.26 [6 H, d, J 6.9,
3
4
3
C
3
4@-CH(CH ) ], 1.48 (3 H, s, 3-CH ), 1.71È2.40 (6 H, m, H-4,5,6),
3 2
Me Si) 17.5 (C-2), 18.5 (C-16), 23.7 [13- CH(CH ) ],29.5 (C-
3
4
3 2
2.97 (1 H, heptet, J 6.9, 4@-CH), 3.00 (3 H, s, 1-CO CH ), 3.90
17), 30.6 (C-1), 32.5 (C-3), 33.5 [13-CH(CH ) ], 44.9 (C-10),
2
3
3 2
46.4 (C-4), 53.1 (15-OCH ), 81.8 (C-5), 123.8 (C-11), 126.3 (C-
3
(1 H, d, J 4.2, H-2), 7.36 (1 H, dd, J 2.1 and 8.4, H-5@), 7.42 (1
H, d, J 8.1, H-6@), 7.82 (1 H, d, J 2.1, H-3@), 9.98 (1 H, d, J 4.2,
2@-CHO), 10.77 (1 H, s, 2-CHO); d (75.47 MHz; CDCl ;
14) 130.7 (C-8), 134.3 (C-12), 147.4 (C-13), 151.4 (C-9), 180.9
(C-15), 183.9 (C-7), 191.9 (C-6); m/z (EI) 330 ([M~` [ CO],
11%), 315 (15), 271 (87), 255 (100), 211(11), 187 (17), 143 (11),
129 (16), 128 (16), 115 (15), 91 (16), 55 (14); m/z (FAB)` 359
C
3
3
Me Si) 19.7 (C-5), 23.5 and 23.7 [4@-CH(CH ) ], 25.1 (1-CH ),
4
3 2
30.5 (3-CH ), 31.7 (C-6), 33.3 (4@-CH), 35.9 (C-4), 40.5 (C-3),
3
43.2 (C-1), 51.2 (1-CO CH ), 60.5 (C-2), 128.0 (C-6@), 131.1 (C-
([M ] H]`, 100%); HRMS found (M)` 358.1783; C
requires 358.1780.
H
O
2
3
21 26
5
3@), 131.1 (C-5@), 135.9 (C-2@), 144.7 (C-1@), 147.4 (C-4@), 175.6 (1-
CO CH ), 192.4 (2@-CHO), 203.8 (2-CHO); m/z (EI)
2
3
346 ([M ] 2H]~`, 27%), 328 (32), 314 (34), 311 (35), 310 (78),
299 (26), 283 (33), 282 (62), 269 (28), 268 (47), 267 (67), 266
(100), 256 (25), 255 (65), 254 (59), 253 (51), 252 (26), 251 (60),
240 (35), 239 (92), 238 (32), 237 (36), 228 (27), 223 (35), 215 (39),
214 (34), 213 (50), 211 (33), 209 (29), 201 (25), 199 (36), 197 (60),
195 (32), 189 (37), 188 (35), 187 (88), 185 (32), 183 (26), 181 (30),
179 (26), 173 (26), 171 (30), 167 (26), 165 (31), 155 (27), 153 (26),
147 (39), 145 (30), 143 (29), 141 (35), 131 (29), 129 (38), 128 (40),
117 (25), 115 (37), 91 (38), 85 (26), 83 (35), 69 (26); HRMS
Methyl 13-isopropyl-7oxopodocarpe-5,8,11,13-tetraen-15-
oate, 11. Yellow oil; d (300.13 MHz; CDCl ; Me Si) 1.27 and
H
3
4
1.28 [6 H, d, J 6.9, 13-CH(CH ) ], 1.53 (3 H, s, H-17), 1.65 (3
3 2
H,s, H-16), 1.72È2.08 (4 H, m, H-1,2,3), 2.17È2.27 (1 H, m, H-3),
2.51 [1 H, d, J 12.6, H-1], 2.98 (1 H, heptet, J 6.9, 13-
CH(CH ) ), 3.72 (3 H, s, 15-OCH ), 6.14 (1 H, s, H-6), 7.44 and
3 2
3
7.45 (2 H, AB, J 6.9, H-11,12), 7.98 (1 H, s, H-14); d (75.47
C
MHz; CDCl ; Me Si) 17.6 (C-2), 23.69 and 23.73 [13-
3
4
CH(CH ) ], 25.0 (C-16), 33.6 [13-CH(CH ) ], 33.9 (C-17), 34.5
3 2
3 2
found [M ] 2H]` 346.1176;
346.1780.
C
H
O ] 2
H
requires
(C-3), 35.3 (C-1), 40.5 (C-10), 50.7 (C-4), 52.3 (15-OCH ), 123.6
21 28
4
3
(C-14), 124.4 (C-11), 126.4 (C-6), 130.0 (C-8), 131.4 (C-12), 147.1
(C-13), 150.4 (C-9), 167.4 (C-5), 176.1 (C-15), 185.1 (C-7); m/z
(EI) 326 (M~`, 93%), 311 (32), 268 (28), 267 (90), 266 (78), 252
(28), 251 (71), 239 (51), 238 (26), 237 (27), 227 (29), 226 (100),
225 (26), 223 (30), 213 (62), 212 (44), 211 (23), 209 (67), 197 (48),
195 (27), 183 (35), 181 (36), 179 (22), 178 (20), 167 (20), 166 (20),
165 (36), 59 (37).
2-(2-Formyl-4-isopropylphenyl)-6-methoxycarbonyl-2,6-
dimethylcyclohexane carboxylic acid 8. Yellow oil; d (300.13
H
MHz; CDCl ; Me Si) 1.16 (3 H, s, 6-CH ), 1.25 [6 H, d, J 6.9,
3
4
3
4@-CH(CH ) ], 1.48, (3 H, s, 2-CH ), 1.92 (6 H, m, H-3,4,5),
3 2
3
2.84 (3 H, s, 6-CO CH ), 2.95 [1 H, heptet, J 6.9, 4@-
2
3
CH(CH ) ], 4.12 (1 H, s, H-1), 7.32 (1 H, dd, J 2.3 and 8.3,
3 2
H-5@), 7.42 (1 H, d, J 8.3, H-6@), 7.84 (1 H, d, J 2.3, H-3@), 10.75
13-Isopropyl-7-oxopodocarpe-5,8,11,13-tetraen-4,6-carbo-
(1 H, s, 2@-CHO); d (75.47 MHz; CDCl ; Me Si) 19.7 (C-4),
lactone, 12. White solid; M.p. 191È192 ¡C; d (300.13 MHz;
C
3
3
4
H
23.5 and 23.7 [4@-CH(CH ) ], 26.8 (6-CH ), 28.5 (2-CH ), 32.4
CDCl ; Me Si) 1.29 [6 H, d, J 6.9, 13-CH(CH ) ], 1.36È1.42
3 2
3 2
3
3
4
3 2
(C-5), 32.8 [4@-CH(CH ) ], 33.3 (C-3), 39.6 (C-2), 43.2 (C-6),
(1 H, m, H-1), 1.61 (3 H, s, H-17), 1.65 (3 H, s, H-16), 1.83È1.90
(2 H, m, H-2), 2.05È2.18 (2 H, m, H-3), 2.37È2.44 (1 H, m, H-1),
50.9 (6-CO CH ), 55.5 (C-1), 128.4 (C-6@), 131.5 (C-3@,5@), 135.9
2
3
(C-2@), 144.5 (C-1@), 147.2 (C-4@), 175.3 (6-CO CH ), 193.2 (2@-
3.01 [1 H, heptet, J 6.9, 13-CH(CH ) ], 7.46 (1 H, d, J 8.2,
2
3
3 2
CHO); m/z (EI) 360 (M~`, 4%), 284 (28), 255 (25), 239 (46), 231
(28), 213 (100), 197 (39), 187 (50), 147 (66); m/z (FAB) 361 [(M
] H)~`, 10%], 343 (37), 297 (13), 255 (14), 239 (13), 213 (12),
197 (10), 180 (11), 165 (15), 115 (18), 77 (51), 63 (25); HRMS
H-11), 7.52 (1 H, dd, J 8.2 and 2.0, H-12), 8.16 (1 H, d, J 1,9,
H-14); d (75.47 MHz; CDCl ; Me Si) 18.9 (C-2), 21.0 (C-16),
C
3
4
23.7 and 23.8 [13-CH(CH ) ], 24.4 (C-17), 33.8 [13-
3 2
CH(CH ) ], 35.9 (C-3), 38.9 (C-10), 42.3 (C-1), 47.1 (C-4), 124.6
3 2
found [M]` 360.1929; C
H
O requires 360.1937.
(C-14), 125.8 (C-11), 130.7 (C-8), 131.6 (C-12), 142.4 (C-6), 145.6
21 28
5
(C-5), 148.0 (C-13), 148.4 (C-9), 174.0 (C-7), 179.6 (C-15); m/z
(EI) 310 (M~`, 79%), 282 (55), 267 (54), 266 (100), 254 (43), 253
(23), 251 (52), 239 (47), 238 (22), 237 (25), 223 (20), 211 (21), 209
(21), 197 (27), 165 (24), 152 (20), 141 (22), 128 (21), 115 (22).
Methyl 6-hydroxy-13-isopropyl-7-oxopodocarpe-8,11,13-
trien-15-oate, 9. Yellow oil; d (300.13 MHz; CDCl ; Me Si)
H
3
4
1.20 [6 H, d, J 6.9, 13-CH(CH ) ], 1.40 (3 H, s, H-17), 1.53 (3
3 2
H, s, H-16), 1.61È1.78 (5 H, m, H-1,2,3), 2.35 (1 H, dd, J 12.9
and 3.0, H-1), 2.91 (1 H, d, J 13.2, H-5), 2.94 [1 H, heptet, J
Crystallography
6.9, 13-CH(CH ) ], 3.47 (1 H, d, J 2.7, 6-OH), 3.62 (3 H, s,
3 2
15-OCH ), 4.47 (1 H, dd, J 13.5 and 2.7, H-6), 7.31 (1 H, d, J
Single crystals of 12 suitable for a single crystal X-ray determi-
nation were obtained by slow evaporation from a light pet-
roleum solution of this compound at room temperature.
X-Ray data were measured using a Mar Research image plate
system using graphite-monochromated Mo-Ka radiation
(j \ 0.710 73 A) at B293 K. The selected crystal, mounted in
a glass capillary under saturated solvent atmosphere, was
positioned at 70 mm from the plate and 95 frames were taken
at 2¡ intervals using a counting time adequate for the crystal
di†raction pattern. Data analysis was performed with the
XDS program.17 Intensities of 5667 observations were col-
lected, of which 3167 were independent reÑections, giving a
3
8.1, H-11), 7.46 (1 H, dd, J 8.1 and 2.1, H-12), 7.91 (1 H, d, J
2.1, H-14); d (75.47 MHz; CDCl ; Me Si) 16.2 (C-16), 18.0
C
3
4
(C-2), 23.7 [13-CH(CH ) ], 24.1 (C-17), 33.5 [13-CH(CH ) ],
3 2
3 2
37.1 (C-3), 37.8 (C-1), 38.4 (C-10), 44.5 (C-4), 50.7 (C-5), 51.9
(15-OCH ), 72.2 (C-6), 124.1 (C-11), 125.3 (C-14), 128.2 (C-8),
3
133.5 (C-12), 147.3 (C-13), 153.1 (C-9), 179.1 (C-15), 200.1 (C-7);
m/z (EI) 345 ([M ] H]~`, 28%), 344 (33), 326 (36), 311 (32),
299 (25), 298 (65), 285 (43), 284 (45), 267 (38), 266 (35), 256 (26),
255 (45), 251 (41), 241 (46), 239 (63), 238 (41), 237 (25), 228 (22),
226 (47), 223 (26), 216 (51), 215 (100), 213 (33), 209 (31), 199
(29), 197 (37), 195 (25), 187 (45), 181 (29), 155 (25), 145 (29), 141
(26), 129 (33), 128 (33), 115 (27), 91 (28), 85 (41), 83 (59), 69 (26),
R
of 0.0674. The structure was solved by direct methods
int
59 (45); HRMS found (M)` 344.1986; C
344.1988.
H
O
requires
using SHELXS18 and reÐned by full-matrix least-squares
reÐnement methods on F2 using the SHELX97 software
package.19 Anisotropic displacements were reÐned for all non-
hydrogen atoms. Hydrogen atoms bonded to carbon atoms
were introduced in the reÐnement at idealised geometric posi-
21 28
4
Methyl 5-hydroxy-13-isopropyl-6,7-dioxopodocarpe-8,11,13-
trien-15-oate, 10. Yellow oil; d (300.13 MHz; CDCl ; Me Si)
H
3
4
1096
New J. Chem., 2001, 25, 1091È1097

View Article Online
3
R. A. Franich and P. D. Gagdil, Physiol. Plant Pathol., 1983, 23,
183.
Y. Ohtsuka and A. Tahara, Chem. Pharm. Bull., 1978, 26, 2007.
J. A. S. Cavaleiro, G. M. S. F. C. Nascimento, M. G. M. S. Neves,
M. T. Pinto, A. J. D. Silvestre and M. G. H. Vicente, T etrahedron
L ett., 1996, 37, 1893.
A. J. D. Silvestre, S. M. C. Monteiro, A. M. S. Silva, J. A. S.
Cavaleiro, V. Felix, P. Ferreira and M. G. B. Drew, Monatsh.
Chem., 1998, 129, 1183.
tions with a U \ 1.2 U of the parent carbon atom. The
iso
eq
absolute stereochemistry of the structure was assigned from
the known chirality of the substituents. The structure was
reÐned on F2 to convergence using SHELXL.19 The Ðnal
4
5
reÐnement of 214 parameters converged to R \ 0.1163 and
1
wR \ 0.2296 for all unique hkl data and to R \ 0.0828 and
6
7
2
1
wR \ 0.2126 for 2406 observed reÑections with I [ 2p(I).
2
Crystal data. C
H
O , M \ 310.38, orthorombic, space
group P2 2 2 , a \ 8.776(11), b \ 10.233(16), c \ 18.853(24)
H. Erdtman and L. Malmborg, Acta Chem. Scand., 1970, 24,
2252; M. Ohta, Pharm. Bull. Jpn., 1956, 4, 273; Y. T. Pratt, J.
Chem. Soc., 1951, 73, 3803; P. F. Ritchie, T. F. Sanderson and
L. F. McBurney, J. Am. Chem. Soc., 1954, 76, 723.
B. Gigante, A. M. Lobo, M. J. Marcelo-Curto, S. Prabhakar,
H. S. Rzepa, A. J. Slawin and D. J. Williams, J. Nat. Prod., 1989,
52, 85.
20 22
3
1 1 1
A, U \ 1693(4) AŽ 3, Z \ 4, k \ 0.081 mm~1.
CCDC reference number 163568. See http://www.rsc.org/
suppdata/nj/b1/b103737b/ for crystallographic data in CIF or
other electronic format.
8
9
P. G. Baraldi, A. Barco, S. Benetti, S. Manfredini, G. P. Pollini,
D. Simoni and V. Zanirato, T etrahedron, 1988, 44, 6451.
Acknowledgements
Thanks are due to FCT for funding research unit no. 62/94.
One of us (S. M. C. S. M.) thanks PRAXIS XXI for a PhD
grant (BD/15786/98).
10 J. Geiwitz and E. Haslinger, Helv. Chim. Acta, 1995, 78, 818.
11 R. Pappo, D. S. Allen, Jr., R. U. Lemieux and W. S. Johnson, J.
Org. Chem., 1956, 21, 478; M. G. Reinecke, L. R. Kray and R. F.
Francis, J. Org. Chem., 1972, 37, 3489; M. Shamma and H. R.
Rodriguez, T etrahedron, 1968, 24, 6583.
12 G. Stork and M. Kahn, T etrahedron L ett., 1983, 24, 3951.
13 E. Wenkert, R. W. J. Carney and C. Kaneco, J. Am. Chem. Soc.,
1961, 83, 4440.
14 D. Cremer and J. A. Pople, J. Am. Chem. Soc., 1975, 97, 1354.
15 C. R. Enzel and I. Wahlberg, Acta Chem. Scand., 1969, 23, 871.
16 A. Bax, J. Magn. Reson., 1984, 57, 314.
17 W. Kabsch, J. Appl. Crystallogr., 1988, 21, 916.
18 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467.
19 G. M. Sheldrick, SHELX-97, University of Gottingen, Germany,
1997.
References
1
L. F. Fieser and W. P. Campbell, J. Am. Chem. Soc., 1938, 60,
2631.
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