New methyl dehydroabietate derivatives: Synthesis and structural characterization

Article abstract of DOI:10.1007/PL00010130

The synthesis of some new chalcone and pyrazole type derivatives of methyl dehydroabietate is described. All compounds were exhaustively characterized using NMR and MS techniques. In order to confirm the information obtained by those techniques, the X-ray

Full text of DOI:10.1007/PL00010130

Monatshefte fuÈr Chemie 129, 1183±1197 (1998)
New Methyl Dehydroabietate Derivatives:
Synthesis and Structural Characterization
1
1
1
Â
Â
Armando J. D. Silvestre , Sõlvia M. C. Monteiro , Artur M. S. Silva , Jose A.
1
S. Cavaleiro1;Ã, Võtor M. S. Felix , Paula Ferreira , and Michael G. B. Drew
1
2
Â
Â
1
Department of Chemistry, University of Aveiro, P-3810 Aveiro, Portugal
2
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 2AD, UK
Summary. The synthesis of some new chalcone and pyrazole type derivatives of methyl dehydro-
abietate is described. All compounds were exhaustively characterized using NMR and MS tech-
niques. In order to con®rm the information obtained by those techniques, the X-ray single crystal
structures of methyl 12-acetyldehydroabietate and methyl 12-(4-methoxycinnamoyl)-dehydroabie-
tate were determined. Molecular mechanics calculations were performed in order to evaluate the
steric in¯uence of the bulk of the C-12 substituent on the conformational preference of the isopropyl
group in these derivatives. The energy barriers of 52.3 and 53.6 kJ/mol found for the two compounds
indicated that the C-12 substituent hinders the free rotation of the isopropyl group in both cases.
Keywords. Chemical transformation; Methyl dehydroabietate; Chalcones; Pyrazoles; Pyrazolines.
Neue Methyldehydroabietatderivative: Synthese und strukturelle Charakterisierung
È
Zusammenfassung. Die Synthese einiger neuer Derivate des Dehydroabietinsauremethylesters vom
Typ der Chalkone und Pyrazole wird beschrieben. Alle Verbindungen wurden mit Hilfe von NMR-
und MS-Techniken charakterisiert. Um die Ergebnisse dieser Techniken zu sichern, wurden
È
È
Rontgen-Einkristallstrukturanalysen des 12-Acetyldehydroabietinsauremethylesters und des entspre-
chenden (12-(4-Methoxycinnamoyl)-Derivates durchgefuÈhrt. Mittels molekuÈlmechanischer Berech-
nungen wurde der Ein¯uû der RaumerfuÈllung des Substituenten in Position 12 auf die Konformation
der Isopropylgruppe in diesen Derivaten studiert. Energiebarrieren von 52.3 und 53.6 kJ/mol fuÈr
diese beiden Verbindungen weisen darauf hin, daû die freie Rotation der Isopropylgruppe in beiden
È
Fallen sterisch gehindert ist.
Introduction
Pine resin is a very abundant renewable source mainly composed by diterpenic
resin acids of the general formula C19H29COOH. This raw material has a wide
range of industrial uses and is also a source of ®ne chemicals [1].
Among resin acid, those of the abietic acid (1) type are the most abundant; they
are also the most versatile for chemical synthesis due to the presence of a
conjugated double bond system.
Ã
Corresponding author

1184
A. J. D. Silvestre et al.
Fig. 1
Dehydroabietic acid (2) can be easily obtained by catalytic dehydrogenation of
abietic type resin acids. A considerable interest has been devoted to this easily
available compound as a starting material, either as free acid or ester, for the
synthesis of other important natural and/or bioactive compounds mainly through
transformations that involve the benzylic or aromatic positions of the molecule. In
this way, oxygenated derivatives of methyl dehydroabietate (3) can be obtained by
various methods [2±6] and are well known for their antifungal properties [7]; also,
reactions of the aromatic moiety, involving various substitution reactions [8±13]
and ozonolysis [14, 15] have been used in the synthesis of several other bioactive
products [16±18].
It is well known that many natural compounds, or certain synthetic analogues,
might have important applications as agrochemicals, pharmaceutical drugs, food
additives, etc. Flavonoids and pyrazoles are included in such types of compounds;
therefore, studies on the synthesis of new molecular entities of such types can give
access to other potentially important compounds.
In the present case, a programme was started a few years ago aiming at the
synthesis of new value added compounds from chemical transformations of raw
materials easily available from vegetal sources [4, 19, 20]. Considering, at the same
time, our previous experience on the synthesis of chalcone and pyrazole derivatives
[21, 22], synthetic studies have been undertaken to obtain new chalcone,
cinnamylideneacetophenone, ꢀ-diketone, and pyrazole derivatives from methyl
12-acetyldehydroabietate (4), a reagent easily available by Friedel-Crafts acylation
of 3 [9].
Results and Discussion
Syntheses
The chalcone-type compound methyl 12-( p-methoxycinnamoyl)dehydroabietate
(5) and the cinnamylideneacetophenone derivative methyl 12-cinnamalacetyldehy-
droabietate (6) were obtained in good yields by base (NaH) catalyzed aldol
condensation of methyl 12-acetyldehydroabietate (4) with p-methoxybenzaldehyde
and cinnamaldehyde at room temperature in dry THF (Scheme 1).
Synthesis of the ꢀ-diketone 7 from condensation of 4 with m-methoxybenzoyl
chloride or with the corresponding methyl or ethyl esters under the same conditions
as mentioned for compounds 5 and 6 was not successful. However, ꢀ-diketone 7

Methyl Dehydroabietate Derivatives
1185
Scheme 1. i, dry THF, NaH, p-methoxybenzaldehyde, r.t., ii, dry THF, NaH, cinnamaldehyde, r.t.
Scheme 2. i, dry THF, butyl lithium, m-methoxybenzoyl chloride, ꢀ78ꢁC
was obtained by condensation of 4 with m-methoxybenzoyl chloride in presence of
butyl lithium at low temperatures (Scheme 2).
Compounds 5, 6, and 7 were tested as precursors in the synthesis of pyrazole
derivatives by reaction with hydrazine hydrate in re¯uxing methanol. The reaction
between 5 and hydrazine hydrate was monitored by TLC; after 5 hours, all starting
material was consumed with the formation of only one reaction product which,
however, decomposed immediately when the solvent was removed, forming a
complex mixture of products from which pyrazole 9 and compound 10 were
isolated (Scheme 3).
This unstable compound was expected to be the pyrazoline 8 since it is well
known that such type of compounds are frequently very unstable intermediates in
the syntheses of pyrazoles [23, 24], and this was con®rmed by NMR and MS
analysis of a reaction carried out in CD3OD. Attempts were made to improve the
yield of 9 through the addition of an oxidizing agent (aqueous KMnO4) to the
reaction media (using THF as solvent); however, no signi®cant changes in the yield
of the pyrazole 9 were found.

1186
A. J. D. Silvestre et al.
Scheme 3. i, methanol, hydrazine hydrate, re¯ux
Scheme 4. i, methanol, hydrazine hydrate, re¯ux
Attempts to prepare pyrazole derivatives from compound 6 were unsuccessful,
yielding very complex mixtures. When the ꢀ-diketone 7 was treated with
hydrazine hydrate, the desired pyrazole 11 was obtained in 64% yield (Scheme 4).
Structural characterization
1
The H and 13C NMR spectra of methyl dehydroabietate (3) can be found in the
literature [25±28] and were the basis for the assignments of the NMR resonances of
1
the new compounds. The H and 13C NMR spectra of the diterpenic part of
molecules 4±11 have many similarities with those of compound 3, and therefore
most protons and carbons could be immediately assigned; in some cases, these
1
assignments were further con®rmed by using COSY (1H, H) and HETCOR
(1H, 13C) experiments. The quaternary carbons C-8, 9, 12, and 13 could not be
assigned directly.
The assignment of the quaternary carbons of methyl 12-acetyldehydroabietate
(4) was performed using a one-dimensional selective INEPT experiment [29]. In
the case of compound 4, H-11 (ꢁ ˆ 7.40 ppm) and H-15 (ꢁ ˆ 3.47 ppm) were
irradiated; the connectivities found in each case and the corresponding 13C
resonance assignments are shown in Table 1. The results of this experiment are in
agreement with our previous assignments of the resonances of C-10, 14, 16, 17,
and 12-CO. No signal enhancement was observed for the resonance at
ꢁ ˆ 146.5 ppm which was then assigned to C-9.

Methyl Dehydroabietate Derivatives
1187
Table 1. Signal enhancements observed by irradiation of the resonances of H-11 and H-15 in
compound 4
1H irradiation (ꢁ, ppm)
13C signal enhancements (ꢁ, ppm)
7.40 (H-11)
36.8 (C-10), 138.7 (C-8),
144.9 (C-13), 203.3 (12-CO)
24.0 and 24.2 (C-16, 17), 126.5
(C-14), 136.3 (C-12),
3.47 (H-15)
144.9 (C-13)
The NMR data for compound 4 show that the methyl groups 16 and 17 are no
1
longer equivalent, appearing with distinct H (ꢁ ˆ 1.19 and 1.21 ppm) and 13C
(ꢁ ˆ 24.0 and 24.2 ppm) resonances. This behaviour is common to compounds 4±
11. In order to understand this fact, a NOE experiment has been carried out. Upon
irradiation of the 12-COCH3 resonance (ꢁ ˆ 2.55 ppm), NOE effects were observed
at H-11 (ꢁ ˆ 7.40 ppm), but not on the isopropyl group. This result indicates that
the 12-COCH3 protons are closer to H-11 than to H-16,17.
An X-ray single crystal diffraction analysis was undertaken for 4 in order to
establish its overall molecular stereochemistry. The molecular structure including
the labelling scheme is shown in Fig. 2. As expected for diterpenic compounds
[30], rings A and B show a trans ring junction with two methyl groups in axial
positions of the six membered rings. Selected torsion angles1 show a classical chair
conformation and a half-chair conformation for rings A and B, respectively.
Fig. 2. Molecular structure of compound 4 with labelling scheme (30% thermal ellipsoids);
disordered methyl groups are shown in one position only for clarity reasons
1
Additional material to the structure determination, comprising atomic coordinates, thermal
parameters, all bond lengths, angles, and selected endocyclic torsion angles may be ordered from
Fachinformationszetrum Karlsruhe, Gesellschaft fuÈr wissenschaftlich-technische Information mbH,
D-76344 Eggenstein-Leopoldshafen, Federal Republic of Germany, referring to the deposition
number CSD-59457, the names of the authors, and the citation of the present paper.

1188
A. J. D. Silvestre et al.
The proximity of H-11 to 12-COCH3 as suggested by the NMR data is also
observed in the solid state: the intramolecular distance between H-11 and one of
Ê
the protons of 12-COCH3 (H(11)Á Á Á(H(111) ˆ 2.35 A) is comparable to the sum of
the van der Waals radii for two hydrogen atoms. On the other hand, in spite of the
disorder found for the methyl groups of the isopropyl group, its protons are too far
from the 12-COCH3 protons for any NOE effect to be observed.
1
The assignments of the H and 13C resonances of compounds 5 were made by
comparing its spectra with the spectroscopic data obtained for compounds 3 and 4,
and also using a HETCOR experiment; the latter allowed the assignment of C-11,
C-14, C-ꢂ, and C-10. In this compound, H-ꢂ and H-ꢀ resonances appear as
doublets (J ˆ 16.0 Hz) at ꢁ ˆ 9.94 and 7.35 ppm, respectively, indicating a trans
stereochemistry of this double bond. In order to evaluate the spatial orientation of
the side chain at position 12, a NOESY has been recorded. In this spectrum, only a
very weak NOE cross peak was observed between H-ꢂ and H-11, and no NOE
cross peaks were observed between H-ꢂ and the isopropyl protons.
A single crystal X-ray structure determination for 5 was carried out. The
molecular structure and atom numbering scheme is shown in Fig 3. The overall
geometry of 5 is comparable to that found for 4, apart from small details: in
compound 5, the carbon atoms C(10), C(7), and C(121) deviate by ꢀ0.14(1),
Ê
0.16(1), and ꢀ0.28(1) A from the best least squares plane de®ned by the carbon
atoms of the aromatic ring of the dehydroabietic skeleton. The pronounced
deviation exhibited by C(121) is probably the result of the minimization of the
steric interactions between the bulky aromatic side chain and the isopropyl group.
In compound 4, these atoms are co-planar with the carbon atoms of the aromatic
ring. The analysis of intramolecular distances for compound 5 reveals that H-11,
H-ꢂ, and the isopropyl protons are too far from each other to establish any type of
Fig. 3. Molecular structure of compound 5 with labelling scheme (30% thermal ellipsoids)

Methyl Dehydroabietate Derivatives
1189
interaction in the solid state. This observation is therefore consistent with the
NOESY results.
The above observation that the methyl groups 16 and 17 of compounds 4±11
1
show different H and 13C chemical shifts due to steric hindrance caused by the
substituent at C-12 prompted us to perform molecular mechanics calculations on
compounds 4 and 5 in order to evaluate the steric in¯uence of the C-12 substituent
on the conformational preference of the isopropyl group. Steric energy pro®les
were obtained for the rotation of isopropyl groups around of the bond C-13-C15
changing the torsion angle C-14-C-13-C-15-C-16 (see Experimental for further
details). The pro®les obtained for both compounds are very alike showing two
rotational barriers with similar energies. The energy minima are ¯at. However, the
X-ray torsion angle C-14-C-13-C-15-C-16 of 80.5(8)ꢁ for compound 4 is located in
one of the broad minima. The disorder found for the methyl groups in compound 4
leads to two different values of 60.1(10)ꢁ and 98.6(12)ꢁ for that torsion angle.
The rotational barriers of 52.3 and 53.6 kJ/mol for 4 and 5 indicate that in both
compounds rotation of the isopropyl group is hindered by the C-12 substituent. The
similarity of these two values suggests that steric hindrance is independent of the
bulk of the C-12 substituents in compounds 4 and 5. As discussed above for
compound 5, C(121) is signi®cantly bent out of the plane of the aromatic ring of
the dehydroabietic skeleton; this fact can contribute to the reduction of energy
barrier of compound 5.
The assignment of the proton resonances of the side chain of compound 6
was based on a 2D COSY experiment. Starting from the resonance of H-ꢂ
(ꢁ ˆ 6.61 ppm) we have assigned the other resonances of the ꢂ,ꢀ,ꢃ,ꢁ-unsaturated
system at 7.18, 6.90, and 6.98 ppm to the resonances of H-ꢀ, H-ꢃ, and H-ꢁ. The
coupling constants (Jꢂ;ꢀ ˆ 15.2 Hz and Jꢃ;ꢁ ˆ 15.4 Hz) indicate a trans-trans stereo-
chemistry of this unsaturated system. This stereochemistry was also con®rmed by a
NOE experiment: upon irradiation of the resonance of H-ꢂ (ꢁ ˆ 6.61 ppm), NOE
effects were observed on the proton resonances of H-ꢃ (ꢁ ˆ 6.98 ppm) and H-11
(ꢁ ˆ 7.20 ppm). These results show that the stereochemistry of the double bond is
as shown in Scheme 1. The NOE effect con®rms the closer proximity of the side
chain to H-11 rather than to the isopropyl group.
The NMR spectroscopic characterization of the ꢀ-diketone 7 was achieved by
comparison with data from previous compounds and based on HETCOR experi-
ments. The resonance at 6.42 ppm is characteristic of ꢂ-enolic protons (attributed
to H-20), and the broad resonance at 16.60 ppm is characteristic of hydrogen
bonded OH groups and indicates that compound 7 exists mainly in the enol form.
1
The assignment of H and 13C resonances of compound 10 was performed by
comparing its spectroscopic characteristics with those from other compounds (in
particular, 5). H-20 and H-30 resonances appear as multiplets at 3.26 and 5.26 ppm;
the assignment of the corresponding 13C resonances was possible via the HETCOR
spectra. The resonance of H-15 appears as a heptet of doublets due to coupling
with H-16,17 (J ˆ 6.1 Hz) and to long distance coupling with H-11 (J ˆ 1.2 Hz).
The assignment of H-11 was based on a NOESY spectrum: NOE cross-peaks were
observed between the signal at 7.30 ppm and the signals at 1.17 ppm (H-20) and
3.26 ppm (H-20), therefore con®rming the assignment of the former resonance to H-
11; on the other hand, NOE cross-peaks were also found between the signal at

1190
A. J. D. Silvestre et al.
ꢁ ˆ 7.05 ppm and the resonances of H-7 and H-16,17, con®rming the assignment of
H-14.
The resonances of quaternary carbons of compound 10 were assigned from an
INEPT experiment: upon irradiation of H-300, 500 (ꢁ ˆ 6.91 ppm), enhancements
were observed at the signals at 159.0 and 135.2 ppm which were therefore assigned
to C-400 and C-100. Less intense signal enhancements were also observed at 146.7
and 137.7 ppm, which were then attributed to C-9 and C-12. These last signal
enhancements were due to the simultaneous irradiation of H-14.
1
The assignments of the H NMR resonances of the pyrazoles 9 and 11 were
made taking into account the spectra of their precursors 5 and 7. The resonance of
H-40 was assigned at 6.53 and 6.60 ppm for 9 and 11. 13C NMR resonances were
also assigned by comparison with those of previous compounds and based on a
HETCOR experiment. The resonances of the quaternary carbons C-8 (ꢁ ˆ
136.2 ppm) and C-9 (ꢁ ˆ 147.1 ppm) were assigned through an INEPT experiment
by irradiation of the H-7 resonance (ꢁ ˆ 2.94 ppm). This experiment also con®rmed
the previous assignments of C-5, 6, and 14 at 44.7, 21.6, and 126.3 ppm,
respectively. As expected, the resonances of C-30,50 were not detected due to the
existence of tautomeric forms [31].
The unstable pyrazoline 8 was identi®ed by 1H NMR through the assignment of
the resonances of H-40 and H-50. The resonances of H-40 protons were assigned
based on a COSY experiment and appear at 3.36±3.49 ppm (overlapped with H-15
resonance) and at 1.20 ppm. H-50 resonates at 4.84 ppm overlapped with the water
signal.
The interpretation of the mass spectra of the synthesized compounds can be
based on the characteristic fragmentations of methyl dehydroabietate 3 [25, 32±35]
and of the substituent groups present in position 12 of the other synthesized
derivatives.
‡
‡
Fragments such as those at m/z ˆ 91 (C7H7) and m/z ˆ 121 (C9H13) , which
are typical of 3, can be found in the mass spectra of the new compounds; however,
the most relevant fragments correspond to the loss of 10-CH3 (M ꢀ15) followed
‡Á
‡Á
by the loss of HCO2CH3 (M ꢀ75). These fragments occur with retention of the
12-substituent, and by comparing the m/z values of the fragments with those of the
corresponding fragments of 3, one can con®rm the mass of such substituents.
Characteristic fragmentations of the carbonylic side chains of compounds 4±7
involve mainly the cleavage of C±C bonds around the 12-CO group [36].
Apart from the fragmentation of the diterpenic moiety of the molecule, the
mass spectra of the isomeric compounds 9 and 11 also show the characteristic
fragmentations of pyrazole compounds. The intense molecular ion observed in
both cases is common with this type of compounds, as well as the fragments at
m/z ˆ 240 and 354 resulting from the cleavage of the pyrazole ring [37].
The molecular ion for compound 10 is not observed in its mass spectrum;
however, an intense fragment at m/z ˆ 474 can be observed which results from the
loss of H2NNH2. The molecular ion is so unstable that it could not be detected even
‡
when FAB ionization was used. Under those conditions, the highest mass observed
was at m/z ˆ 475, corresponding to the same fragment detected by EI ionization.
Finally, the identity of the pyrazoline 8 was also con®rmed since its molecular ion
can easily be detected at m/z ˆ 488.

Methyl Dehydroabietate Derivatives
1191
Experimental
Melting points are uncorrected and were determined on a Reichert Thermovar apparatus ®tted with a
1
microscope. H and 13C NMR spectra were taken in CDCl3 solutions (not degassed), except when
another solvent is speci®ed, on a Bruker AMX 300 spectrometer at 300.13 and 75.47 MHz (TMS as
internal reference). 2D experiments were obtained using Bruker standard microprograms. 2D COSY
spectra were collected in a 1024Â 256 matrix. In the 2D heteronuclear shift correlation (HETCOR)
the initial matrix of 2048Â512 was zero ®lled to 2048Â1024; the relaxation delay was 2 s. The phase
sensitive NOESY spectra were acquired in a 2048Â512 matrix with a mixing time and a relaxation
delay of 1 s each and then processed in a 2048Â1024 matrix. One-dimensional selective INEPT
experiments (INAPT sequence) were acquired using a 2 s relaxation delay; Á1 and Á2 of the pulse
sequence were optimized for a 7 Hz long-range JꢂC;H† coupling constant. Low (MS) and high re-
solution (HRMS) mass spectra were obtained at 70eVelectron impact ionisation using a VG Autospec
Q mass spectrometer. Elemental analyses were performed on a Carlo Erba-Strumentazione, Ele-
mental Analiser-Mod. 1106.
Preparative thin layer chromatography (TLC) was carried out on silica gel plates (Riedel silica
gel 60 DGF254). Column chromatography was also performed on silica gel (Merck silica gel 60,
70±230 mesh). All other chemicals and solvent used herein were obtained from commercial sources
and used as received or dried using standard procedures. Light petroleum was the fraction of b.p.
40±60ꢁC. Elemental analysis of novel compounds were found to be in agreement with the calculated
values.
Note on nomenclature
The names of compounds 4±11 in the experimental part were derived according to IUPAC rules [38],
considering all compounds as derivatives of methyl dehydroabietate (3). However, for a clear dis-
cussion and presentation of experimental NMR spectroscopic data, the numbering of side chains
presented in the schemes is not totally consistent with IUPAC rules.
Methyl dehydroabietate (3; C21H30O2)
Methyl dehydroabietate was obtained by catalytic dehydrogenation of methylated resin according to
known methods [1].
Methyl 12-acetyldehydroabietate (4; C23H32O3)
Methyl 12-acetyldehydroabietate was obtained by Friedel-Crafts acylation of 3 according to known
methods [9].
Yield: 3.26 g (41%); m.p.: 135.4±136.1ꢁC (recrystallized from a mixture of light petroleum:di-
1
chloromethane (1:1); Ref. [9]: m.p.: 133.5±134.0ꢁC); H NMR (300 MHz, ꢁ CDCl3): 1.19 and 1.21
(6H, d, J ˆ 7.4, H-16, 17), 1.21 (3H, s, H-20), 1.28 (3H, s, H-19), 1.40±1.57 (2H, m, H-1,6), 1.65±
1.91 (5H, m, H-2,3,6), 2.22 (1H, dd, J ˆ 2.1 and 12.5, H-5,), 2.32 (1H, d, J ˆ 12, H-1), 2.55 (3H, s,
12-COCH3), 2.90 (2H, m, H-7), 3.47 (1H, hept, J ˆ 6.8, H-15), 3.67 (3H, s, 4-COOCH3), 7.04 (1H, s,
H-14), 7.40 (1H, s, H-11) ppm; 13C NMR (75 MHz, ꢁ, CDCl3): 16.4 (C-19), 18.4 (C-2), 21.4 (C-6),
24.0 and 24.2 (C-16,17), 25.1 (C-20), 28.6 (C-15), 29.9 (C-7), 30.5 (12-COCH3), 36.5 (C-3), 36.8
(C-10), 37.8 (C-1), 44.6 (C-5), 47.5 (C-4), 52.0 (4-COOCH3), 124.3 (C-11), 127.0 (C-14), 136.3
(C-12), 138.7 (C-8), 144.9 (C-13), 146.5 (C-9), 178.9 (C-18), 203.3 (12-CO) ppm; MS: m/z ˆ 356
‡Á
(M , 40%), 341 (27), 297, (6), 281 (100), 239 (9), 227 (6), 215 (11), 197 (8), 153 (6), 128 (7), 115
(7), 59 (10).

1192
A. J. D. Silvestre et al.
Methyl 12-(p-methoxycinnamoyl)dehydroabietate (5; C31H38O4)
15 mg NaH (0.62 mmol) was added to a solution of 108 mg 4 (0.303 mmol) in dry 15 ml THF under a
N2 atmosphere. After 15 min, 56 mg p-methoxybenzaldehyde (0.41 mmol) were added, and the
mixture was stirred for 12 h. Then the mixture was poured into H2O and extracted with CH2Cl2, the
organic layer was dried over anhydrous Na2SO4, and the solution concentrated on a rotary evap-
orator. The residue was then puri®ed by TLC eluting with light petroleum: CH2Cl2 (1:1) and
crystallized from a mixture of light petroleum: CH2Cl2 (1:1).
1
Yield: 115 mg (80%); m.p.: 129.3±130.5ꢁC; H NMR (300 MHz, ꢁ, CDCl3): 1.19 and 1.22 (6H,
d, J ˆ 6.8, H-16,17), 1.22 (3H, s, H-20), 1.28 (3H, s, H-19), 1.43±1.54 (2H, m, H-1,6), 1.66±1.79
(3H, m, H-2,3), 1.81±1.90 (2H, m, H-3,6), 2.24 (1H, dd, J ˆ 2.2 and 12.4, H-5), 2.27 (1H, d, J ˆ
12.7, H-1), 2.94 (2H, m, H-7), 3.19 (1H, hept, J ˆ 6.8, H-15), 3.68 (3H, s, 4-COOCH3), 3.85 (3H, s,
40-OCH3), 6.92 (2H, d, J ˆ 8.8, H-30, 50), 6.94 (1H, d, J ˆ 16.1, H-ꢂ), 7.05 (1H, s, H-14), 7.21 (1H, s,
H-11), 7.35 (1H, d, J ˆ 16.1, H-ꢀ), 7.49 (2H, d, J ˆ 8.8, H-20, 60) ppm; 13C NMR (75 MHz, ꢁ,
CDCl3): 16.5 (C-19), 18.4 (C-2), 21.5 (C-6), 24.1 and 24.3 (C-16,17), 25.0 (C-20), 29.3 (C-15), 30.0
(C-7), 36.6 (C-3), 36.9 (C-10), 37.8 (C-1), 44.8 (C-5), 47.6 (C-4), 52.0 (4-COOCH3), 55.4
(40-OCH3), 114.4 (C-30, 50), 123.6 (C-11), 125.8 (C-ꢂ), 126.5 (C-14), 127.3 (C-10), 130.1 (C-20, 60),
136.7 (C-12), 137.4 (C-8), 144.0 (C-13), 145.8 (C-ꢀ), 146.5 (C-9), 161.6 (C-40), 179.0 (C-18), 198.2
‡Á
(12-CO) ppm; MS: m/z ˆ 474 (M , 100%), 459 (10), 431 (9), 399 (12), 353 (51), 341 (21), 277 (17),
265 (13), 237 (12), 261 (20), 133 (11), 121 (89), 91 (9).
Methyl 12-cinnamalacetyldehydroabietate (6; C32H38O3)
14 mg NaH (0.57 mmol) was added to a solution of 102 mg 4 (0.287 mmol) in dry 15 ml THF under a
N2 atmosphere. After 15 min, 52 mg cinnamaldehyde (0.40 mol) were added and the mixture was
stirred for 12 h. Then the mixture was poured into H2O and extracted with CH2Cl2, the organic layer
was dried over anhydrous Na2SO4 and the solution concentrated on a rotary evaporator. The residue
was then puri®ed by TLC eluting with light petroleum:ethyl acetate (1:1) and crystallized from a
mixture of light petroleum:CH2Cl2 (1:1).
Yield: 105 mg (78%); m.p.: 152.3±154.5 ꢁC; 1H NMR (300 MHz, ꢁ, CDCl3): 1.19 and 1.21 (6H,
d, J ˆ 6.9, H-16,17), 1.22 (3H, s, H-20), 1.28 (3H, s, H-19), 1.43±1.55 (2H, m, H-1,6), 1.65±1.93
(5H, m, H-2,3,6), 2.24 (1H, dd, J ˆ 2.1 and 12.5, H-5), 2.29 (1H, d, J ˆ 12.6, H-1), 2.93 (2H, m, H-
7), 3.20 (1H, hept, J ˆ 6.8, H-15), 3.68 (3H, s, 4-COOCH3), 6.61 (1H, d, J ˆ 15.2, H-ꢂ), 6.90 (1H, d,
J ˆ 15.4, H-ꢁ), 6.98 (1H, m, H-ꢃ), 7.04 (1H, s, H-14), 7.18 (1H, dd, J ˆ 9.9 and 15.2, H-ꢀ), 7.20 (1H,
s, H-11), 7.35 (3H, m, H-30, 40, 50), 7.48 (2H, dd, J ˆ 1.5 and 8.0, H-20, 60) ppm; 13C NMR (75 MHz,
ꢁ, CDCl3): 16.5 (C-19), 18.4 (C-2), 21.5 (C-6), 24.1 and 24.3 (C-16,17), 25.1 (C-20), 29.3 (C-15),
30.0 (C-7), 36.6 (C-3), 36.9 (C-10), 37.8 (C-1), 44.7 (C-5), 47.6 (C-4), 52.0 (4-COOCH3), 123.6 (C-
11), 126.5 (C-14), 126.8 (C-ꢃ), 127.3 (C-20, 60), 128.8 (C-30, 40), 129.2 (C-50), 131.2 (C-ꢂ), 136.0 (C-
10), 136.5 (C-12), 137.5 (C-8), 141.5 (C-ꢁ), 144.1 (C-13), 145.8 (C-ꢀ), 146.5 (C-9), 179.0 (C-18),
‡Á
198.0 (12-CO) ppm; MS: m/z ˆ 470 (M , 100%), 455 (21), 427 (6), 401 (20), 395 (25), 366 (17),
353 (52), 351 (14), 341 (14), 329 (8), 391 (29), 273 (11), 265 (9), 237 (8), 197 (9), 157 (14), 129
(15), 128 (18), 117 (23), 115 (13), 91 (28).
Methyl 12-(3-(3-methoxyphenyl)-3-oxopropanoyl)dehydroabietate (7; C31H38O5)
A solution of 100 mg methyl 12-acetyldehydroabietate 4 (0.280 mmol) in freshly dried 15 ml THF
under a N2 atmosphere was cooled to ꢀ78ꢁC; then 40 ml butyl lithium (1.0 mmol) were added, and
the solution was stirred for 25 min. After that time, 100 ml m-methoxybenzoyl chloride (0.712 mmol)
were added and the mixture was stirred for 3 h. Then the mixture was poured into H2O, acidi®ed to
pH 3 with 1 M HCl, and extracted with CH2Cl2. The organic layer was dried over anhydrous

Methyl Dehydroabietate Derivatives
1193
Na2SO4, the solution was concentrated on a rotary evaporator, and the residue was puri®ed by TLC
eluting with light petroleum:ethyl acetate (9:1); compound 7 was obtained as an oil.
Yield: 15.1 mg (11%); HRMS: found: 490.2692, C31H38O5 requires 490.2719; 1H NMR
(300 MHz, ꢁ, CDCl3): 1.23 (3H, s, H-20), 1.23 and 1.26 (6H, d, J ˆ 6.8, H-16,17), 1.28 (3H, s, H-19),
1.36±1.58 (2H, m, H-1,6), 1.63±1.93 (5H, m, H-2,3,6), 2.23 (1H, dd, J ˆ 2.0 and 12.5, H-5), 2.33
(1H, d, J ˆ 12.2, H-1), 2.93 (2H, m, H-7), 3.44 (1H, hept, J ˆ 6.9, H-15), 3.67 (3H, s, 4-COOCH3),
3.87 (3H, s, 300-OCH3), 6.50 (1H, s, H-20), 7.24 (2H, m, H-14,400), 7.43 (1H, s, H-11), 7.50 (1H, m,
H-500), 7.63 (2H, m, H-200,600), 16.60 (broad, enolic OH) ppm; 13C NMR (75 MHz, ꢁ, CDCl3): 16.5
(C-19), 18.4 (C-2), 21.5 (C-6), 24.2 and 24.4 (C-16,17), 25.0 (C-20), 29.2 (C-15), 29.9 (C-7), 36.6
(C-3), 37.0 (C-10), 37.9 (C-1), 44.7 (C-5), 47.6 (C-4), 52.0 (4-COOCH3), 55.4 (300-OCH3), 98.0
(C-20), 111.9 and 119.5 (C-200,600), 118.5 (C-400), 124.1 (C-11), 126.8 (C-14), 129.6 (C-500), 134.1
(C-100), 136.8 (C-12), 138.2 (C-8), 144.2 (C-13), 147.0 (C-9), 159.8 (C-300), 179.0 (C-18), 184.4 and
191.7 (C-10,30) ppm; MS: m/z ˆ 490 (M‡ꢃ, 30%), 447 (33), 355(33), 341 (100), 338 (17), 313 (11),
283 (29), 265 (18), 143 (17), 135 (64), 107 (16), 85 (14), 83 (21), 77 (14), 55 (10).
Synthesis of methyl 12-(5-(3)-(4-methoxyphenyl)pyrazol-3(5)-yl)dehydroabietate (9)
40 ml Hydrazine hydrate (0.54 mmol) were added to a solution of 101.0 mg methyl 12-(4-methoxy-
cinnamoyl)dehydroabietate (5, 0.213 mmol) in 70 ml methanol under a N2 atmosphere; the mixture
was stirred and re¯uxed for 12 h. The mixture was then poured into H2O and extracted with CHCl3;
the organic layer was dried over anhydrous Na2SO4 and concentrated in the rotary evaporator. The
mixture was then puri®ed by TLC eluting with light petroleum:ethyl acetate (9:1). Two products
were isolated: pyrazole 9 and hydrazine 10. When the reaction was carried out in CD3OD, the direct
NMR analysis of the reaction mixture allowed the identi®cation of pyrazoline 8. Compounds 9 and
10 were obtained as pure oils.
Methyl 12-(5-(3)-(4-methoxyphenyl)pyrazol-3(5)-yl)dehydroabietate (9; C31H38N2O3)
Yield: 19.8 mg (19.2%); HRMS: found 486.2862, C31H38N2O3 requires 486.2882; 1H NMR
(300 MHz, ꢁ, CDCl3): 1.17 and 1.20 (6H, d, J ˆ 6.8, H-16,17), 1.22 (3H, s, H-20), 1.28 (3H, s, H-19),
1.42±1.54 (2H, m, H-1,6), 1.63±1.93 (5H, m, H-2,3,6), 2.24 (1H, dd, J ˆ 2.1 and 12.3, H-5), 2.28
(1H, m, H-1), 2.94 (2H, m, H-7), 3.20 (1H, hept, J ˆ 6.8, H-15), 3.68 (3H, s, 4-COOCH3), 3.85 (3H,
s, 40-OCH3), 6.53 (1H, s, H-40), 6.95 (2H, d, J ˆ 8.8, H-300, 500), 7.06 (1H, s, H-14), 7.22 (1H, s, H-
11), 7.73 (2H, d, J ˆ 8.8, H-200, 600) ppm; 13C NMR (75 MHz, ꢁ, CDCl3): 16.5 (C-19), 18.5 (C-2),
21.6 (C-6), 24.2 and 24.4 (C-16,17), 25.1 (C-20), 29.2 (C-15), 29.8 (C-7), 36.6 (C-3), 36.9 (C-10),
37.9 (C-1), 44.7 (C-5), 47.6 (C-4), 52.0 (4-COOCH3), 55.3 (400-OCH3), 102.7 (C-40), 114.1 (C-300,
600), 125.3 (C-100), 125.7 (C-11), 126.3 (C-14), 126.9 (C-200, 600), 136.2 (C-8,12), 144.4 (C-13), 147.1
(C-9), 179.1 (C-18) ppm; MS: m/z ˆ 487 (36%), 486 (M‡ꢃ, 100), 485 (20), 473 (30), 471 (13), 411
(25), 341 (29), 339 (16), 338 (43), 292 (15), 281 (18), 236 (16), 208 (23), 194 (15), 177 (30), 167
(26), 163 (16), 135 (15), 134 (16), 121 (34), 77 (15), 71 (22), 57 (25), 55 (18).
Methyl 12-(3-hydrazino-3-(4-methoxyphenyl)propanoyl)dehydroabietate (10; C31H42N2O4)
‡
‡
Yield: 12.1 mg (14%); HRMS (FAB ): found 475.2929 (M-H2NNH2 ‡ H) , C31H39O4 requires
475.2848; 1H NMR (300 MHz, ꢁ, CDCl3): 1.17 (3H, s, H-20), 1.20 (6H, m, H-16,17), 1.27 (3H, s, H-
19), 1.41±1.48 (2H, m, H-1,6), 1.61±1.92 (5H, m, H-2,3,6), 2.19 (1H, dd, J ˆ 2.0 and 12.5, H-5), 2.23
(1H, m, H-1), 2.90 (2H, m, H-7), 3.26 (2H, m, H-20), 3.41 (1H, hept d, J ˆ 1.2 and 6.8, H-15), 3.67
(3H, s, 4-COOCH3), 3.81 (3H, s, 400-OCH3), 5.26 (1H, m, H-30), 6.91 (2H, d, J ˆ 8.7, H-300, 500), 7.05
(1H, s, H-14), 7.30 (1H, d, J ˆ 1.2, H-11), 7.35 (2H, d, J ˆ 8.7, H-200, 600) ppm; 13C NMR (75 MHz, ꢁ,
CDCl3): 16.4 (C-19), 18.3 (C-2), 21.3 (C-6), 24.1 and 24.3 (C-16,17), 25.0 (C-20), 28.7 (C-15), 29.9

1194
A. J. D. Silvestre et al.
(C-7), 36.5 (C-3), 36.9 (C-10), 37.8 (C-1) 44.6 (C-5), 47.5 (C-4), 50.7 (C-30), 52.0 (4-COOCH3),
55.3 (400-OCH3), 70.2 (C-200), 113.9 (C-300, 500), 124.0, (C-11), 127.0 (C-200, 600), 127.2 (C-14), 135.2
(C-100), 135.7 (C-12), 139.3 (C-8), 145.2 (C-13), 146.7 (C-9), 159.1 (C-400), 178.9 (C-18), 205.6 (C-
10) ppm; MS: m/z ˆ 476 (39%), 474 (64), 459 (11), 431 (7), 399 (5), 358 (16), 357 (35), 356 (70),
355 (35), 353 (23), 343 (18), 342 (30), 341 (71), 340 (53), 339 (24), 325 (20), 313 (7), 283 (45), 282
(52), 281 (100), 265 (23), 239 (18), 237 (20), 215 (18), 181 (15), 167 (16), 155 (18), 150 (25), 149
(16), 141 (18), 137 (26), 136 (51), 135 (68), 128 (16), 121 (50), 107 (17), 92 (16), 91 (15), 77 (38),
65 (15), 55 (20).
Methyl 12-(5-(4-methoxyphenyl)pyrazolin-3-yl)dehydroabietate (8; C31H40N2O3)
1H NMR (300 MHz, ꢁ, CD3OD): 1.16 and 1.18 (6H, d, J ˆ 2.5, H-16,17), 1.20 (1H, m, H-40) 1.21
(3H, s, H-20), 1.28 (3H, s, H-19), 1.36±1.46 (2H, m, H-1,6), 1.62±1.93 (5H, m, H-2,3,6), 2.14 (1H,
dd, J ˆ 2.0 and 12.1, H-5), 2.34 (1H, d, J ˆ 13.3, H-1), 2.87 (2H, m, H-7), 3.35±3.49 (2H, m, H-
15,40), 3.67 (3H, s, 4-COOCH3), 3.79 (3H, s, 400-OCH3), 4.84 (1H, m, H-50), 6.92 (2H, d, J ˆ 8.7, H-
300, 500), 7.03 (1H, s, H-14), 7.15 (1H, s, H-11), 7.34 (2H, d, J ˆ 8.7, H-200, 600) ppm; MS: m/z ˆ 488
(M‡ꢃ, 66%), 381 (9), 341 (8), 339 (31), 338 (100), 278 (9), 263 (6), 223 (5), 165 (5), 157 (5), 150 (6),
149 (9), 136 (18), 135 (12), 134 (20), 121 (18), 91 (8), 77 (8), 65 (5), 59 (9), 57 (9), 55 (8), 44 (18),
43 (12), 41 (22), 40 (12), 39 (10), 38 (6), 36 (21), 35 (5), 32 (31).
Methyl 12-(5(3)-(3-methoxyphenyl)pyrazol-3(5)-yl)dehydroabietate (11; C31H38N2O3)
20 ml Hydrazine hydrate (0.41 mmol) were added to a solution of 80 mg methyl 12-(3-(3-
methoxyphenyl)-3-oxopropanoyl)dehydroabietate (7, 0.160 mmol) in 70 ml methanol under a N2
atmosphere, and the mixture was stirred and re¯uxed for 12 h. The mixture was then poured into
H2O, extracted with CHCl3, and the organic layer was dried over anhydrous Na2SO4 and
concentrated using the rotary evaporator. The mixture was then puri®ed by TLC eluting with light
petroleum:ethyl acetate (9:1); compound 11 was obtained as an oil.
Yield: 49.7 mg (64%); HRMS: found: 486.2869, C31H38N2O3 requires 486.2882; 1H NMR
(300 MHz, ꢁ, CDCl3): 1.18 and 1.21 (6H, d, J ˆ 6.9, H-16,17), 1.23 (3H, s, H-20), 1.29 (3H, s, H-19),
1.44±1.56 (2H, m, H-1,6), 1.64±1.94 (5H, m, H-2,3,6), 2.25 (1H, dd, J ˆ 2.1 and 12.4, H-5), 2.29
(1H, m, H-1), 2.94 (2H, m, H-7), 3.17 (1H, hept, J ˆ 6.8, H-15), 3.68 (3H, s, 4-COOCH3), 3.88 (3H,
s, 300-OCH3), 6.60 (1H, s, H-40), 6.90 (1H, m, H-400), 7.07 (1H, s, H-14), 7.21 (1H, s, H-11), 7.34 (1H,
m, H-500), 7.40 (2H, m, H-200, 600) ppm; 13C NMR (75 MHz, ꢁ, CDCl3): 16.5 (C-19), 18.4(C-2), 21.6
(C-6), 24.2 and 24.4 (C-16,17), 25.1 (C-20), 29.2 (C-15), 29.8 (C-7), 36.6 (C-3), 36.9 (C-10), 37.9
(C-1), 44.7 (C-5), 47.6 (C-4), 52.0 (4-COOCH3), 55.3 (300-OCH3), 103.3 (C-40), 110.8 (C-200), 113.9
(C-400), 118.2 (C-600), 125.6 (C-11), 126.4 (C-500), 136.4 (C-8,12), 144.4 (C-13), 147.2 (C-9), 159.9
(C-300), 179.0 (C-18) ppm; MS: m/z ˆ 487 (35%), 486 (M‡ꢃ, 100), 485 (22), 471 (15), 412 (15), 411
(45), 386 (12), 369 (10), 356 (11), 355 (11), 354 (14), 342 (18), 341 (65), 340 (13), 339 (27), 338
(68), 311 (14), 281 (36), 236 (39), 222 (12), 208 (62), 194 (32), 179 (15), 177 (80), 167 (11), 165
(15), 163 (26), 149 (33), 145 (28), 136 (24), 135 (23), 134 (22), 133 (19), 123 (37), 121 (32), 117
(20), 115 (11), 111 (11), 109 (12), 107 (15), 105 (20), 97 (15), 95 (15), 91 (21), 89 (26), 85 (15), 83
(20), 8 (19), 77 (31), 73 (16), 71 (24), 69 (33), 67 (17), 63 (17), 57 (42), 55 (46), 51 (25).
Single crystal diffraction analysis
Data collection and processing
The pertinent crystal data and re®nement details for compounds 4 and 5 are given in Table 2. The
crystal data for both compounds were collected with a MAR research image plate system using

Methyl Dehydroabietate Derivatives
1195
Table 2. Crystal data and details of structure re®nement for compounds 4 and 5
Compound
4
5
Molecular Formula
M
C23H31O3
355.48
C31H38O4
474.61
Monoclinic
P21
Crystal system
Space group
Orthorhombic
P212121
Ê
a (A)
Ê
b (A)
7.467(8)
10.813(12)
25.530(14)
(90.0)
6.222(9)
8.153(9)
26.35(2)
94.21(1)
1333(3)
2
Ê
c (A)
ꢀ (ꢁ)
Ê 3
U (A )
2061(3)
Z
4
Dc (g.cmꢀ3
)
1.145
1.182
m (mmꢀ1
F (000)
)
0.074
0.077
772
512
ꢆ range for data collection (ꢁ)
Index ranges
3.3ꢀ26.0
0 ꢄ h ꢄ 8, ꢀ11 ꢄ k ꢄ 12,
ꢀ30 ꢄ l ꢄ 30
2.9ꢀ26.1
0 ꢄ h ꢄ 7, ꢀ9 ꢄ k ꢄ 9,
ꢀ32 ꢄ l ꢄ 32
3764
Measured re¯ections
Independent re¯ections (Rint)
Data/parameters
1838
1542(0.0228)
1542/238
3599(0.0464)
3599/323
a and b in weighting schemes
GOF on F2
0.1457, 0.72
1.053
0.2000, 0.00
1.150
R and Rw (I > 2 ꢅ (I))
R and Rw (all data)
0.0645, 0.1855
0.0848, 0.2079
0.183, ꢀ0.147
0.0880, 0.2672
0.1369, 0.3051
0.680, ꢀ0.313
Largest difference peak and
hole (e Á Aꢀ3
)
Ê
graphite-monochromated MoKꢂ radiation (ꢄ ˆ 0.71073 A). The crystals were positioned at 75 mm
from the image plate. An exposure time of 2 min was used per 2 for each of the 95 frames collected.
Data analysis was carried out with the XDS program [39]. Intensities were not corrected for
absorption effects.
Structure analysis and re®nement
The structures were solved by direct methods. The earlier difference maps obtained for compound 4
revealed the two terminal carbons of one isopropyl group disordered over two positions in the crystal
structure. Then, the coordinates of these two atoms were included in the re®nement, occupying two
alternate positions with occupancy factors of 0.5.
Anisotropic parameters were used for non hydrogen atoms, except for disordered carbon atoms of
compound 4, which were re®ned with individual isotropic temperature factors.
Hydrogen atoms were included in the re®nement in geometric positions giving thermal param-
eters equivalents to 1.2 times those of the atom to which they were attached. The structures were
re®ned by least-square methods on F2 until convergence is achieved. A weighting scheme of the form
2
w ˆ 1=ꢂꢅ2ꢂFo2† ‡ ꢂaP† ‡ bP† with P ˆ ꢂmaxꢂFo2† ‡ 2Fo2†=3 was used. The last difference Fourier
Ê ꢀ3
maps calculated for both compounds showed no peaks with electronic density above 1 eA
.

1196
A. J. D. Silvestre et al.
All calculations were carried out with SHELXS and SHELXL within the SHELX97 package
[40]. The molecular diagrams were drawn with ZORTEP [41].
Molecular mechanics calculations
Molecular mechanics calculations were carried out using the Dreiding force ®eld within the
CERIUS2 package software, release 3.0 [42]. Default values were used for all force ®eld parameters
except stated otherwise. The steric energy pro®les of isopropyl group rotation presented for
compounds 4 and 5 were calculated using the following procedure: X-ray structures of both
compounds were taken as starting models for the corresponding molecular mechanics calculations.
In both cases, the isopropyl group was rotated changing successively the torsion angle C(14)-C(13)-
C(15)-C(16) of 10ꢁ intervals over range of ꢀ180ꢁ to 180ꢁ. A large force constant for a cosine-
Fourier expansion torsion term was used in order to ®x the torsion angle at a particular value. So 36
structures were minimized and an energy pro®le for the rotation of isopropyl group as a function of
the exocyclic torsion angle was obtained. All structures were minimized employing a conjugate
gradient until convergence. High convergence criteria with default parameters were used.
Acknowledgements
Sincere thanks are due to the University of Aveiro for the award of a student's grant to S. M. C.
Monteiro.
References
[1] Zinkel DF, Russell J (eds) (1989) Naval Stores. Pulp Chemicals Assoc, New York
[2] Richtie PF, Sanderson TF, McBurney LF (1954) J Am Chem Soc 76: 723
[3] Ohta MJ (1955) Pharm Bull Japan 75: 289
[4] Cavaleiro JAS, Nascimento GMSC, Neves MGMS, Pinto MT, Silvestre AJD, Vicente MGH
(1996) Tetrahedron Lett 37: 1893
[5] Gigante B, Marcelo-Curto MJ, Lobo AM, Prabhakar S, Slawin AJ, Rezpa HS, Williams DJ
(1989) J Nat Prod 52: 85
[6] Gigante B, Marcelo-Curto MJ, Lobo AM, Prabhakar S, O'Mahoney C, Rezpa HS, Williams DJ
(1991) J Nat Prod 54: 247
[7] Franich RA, Gagdil PD (1983) Physiol Plant Pathol 23: 183
[8] Pratt YT (1951) J Chem Soc C 73: 3803
[9] Fieser LF, Campbell WP (1939) J Chem Soc C 61: 2528
[10] Akita H, Oishi T (1981) Chem Pharm Bull 29: 1567
[11] Akita H, Anasawa A, Oishi T (1981) Chem Pharm Bull 29: 1588
[12] Akita H, Naito T, Oishi T (1980) Chem Pharm Bull 28: 2116
[13] Tahara A, Akita H (1975) Chem Pharm Bull 23: 1976
[14] Akita H, Mori K, Tahara A (1977) Chem Pharm Bull 25: 974
[15] Akita H, Oishi T (1978) Tetrahedron Lett 39: 3733
[16] Matsumoto T, Terao H, Wada M, Mai S (1991) Bull Chem Soc Jpn 64: 2762
[17] Ohtsuka Y, Tahara A (1978) Chem Pharm Bull 26: 2007
[18] Okuda S, Sanai S, Kimura Y, Tamura S, Tahara A (1976) Agric Biol Chem 40: 1327
[19] Silvestre AJD, Cavaleiro JAS, Silva AMS, Delmond B, Filliatre C (1996) Heterocyclic Commun
2: 371
[20] Silvestre AJD, Cavaleiro JAS, Silva AMS, Delmond B, Filliatre C (1997) J Chem Res (S) 228; J
Chem Res (M) 1516
[21] Silva AMS, Tavares HR, Barros AINRA, Cavaleiro JAS (1997) Spectrosc Lett 30: 1655

Methyl Dehydroabietate Derivatives
1197
[22] Silva AMS, Almeida LMPM, Cavaleiro JAS, Foces-Foces C, Llamas-Saiz AL, Fontenas C,
Jagerovia N, Elguero J (1997) Tetrahedron 53: 11645
[23] Reid S (1970) The Photochemistry of Heterocycles. In: Katritzky AR, Boulton AJ (eds)
Advances in Heterocyclic Chemistry, vol 11. Academic Press, New York, p 1
Â
[24] Levai A, Toth G (1995) Trends in Heterocyclic Chem 4: 89
[25] Zinkel DF, Zank LC, Wesolowski MF (1971) Diterpene Resin Acids A Compilation of Infrared,
Mass, Nuclear Magnetic Resonance, Ultraviolet Spectra and Gas Chromatographic Retention
Data. USDA Forest Service, Madison
[26] Jurgens A, Macchesney J (1990) Magn Reson Chem 28: 181
[27] Gigante B, Santos L, Marcelo-Curto MJ (1990) Magn Reson Chem 33: 318
[28] Landucci L, Zinkel DF (1991) Holzforschung 45: 341
[29] Bax A (1981) J Magn Reson 57: 314
[30] Allen FH, Davies JE, Galloy JJ, Johnson O, Kennard O, Macrae CF, Watson DG (1991) J Chem
Inf Comp Sci 31: 204
[31] Begtrup M, Boyer G, Cabildo P, Cativiela C, Claramunt RM, Elguero J, Garcia JI, Toiron C,
Vedsꢀ P (1993) Magn Reson Chem 31: 107
[32] Genge C (1959) Anal Chem 31: 1750
[33] Enzell C, Wahlberg I (1969) Acta Chem Scand 23: 871
[34] Chang T, Mead T, Zinkel DF (1971) J Am Oil Chem Soc 48: 455
Ã
[35] Ramalho L, Gigante B, Marcelo-Curto MJ, Florencio F (1995) Eur Mass Spectrom 1: 389
[36] Mabry TJ, Markham KM (1975) Mass Spectrometry of Flavonoids. In: Harborne JB, Mabry TJ,
Mabry H (eds) The Flavonoids. Chapman and Hall, London, p 78
[37] Elguero J (1984) Pyrazoles and Their Benzo Derivatives. In: Potts KT (ed) Comprehensive
Heterocyclic Chemistry, vol 5. Pergamon Press, Oxford, p 167
[38] Rigaudy J, Klesney SP (eds) (1979) Nomenclature of Organic Chemistry ± Sections A, B, C, D,
E, F and H. Pergamon Press, Oxford, 1979
[39] Kabsch W (1988) J Appl Crystallogr 21: 916
[40] Sheldrick GM (1997) SHELX-97, University of Gottingen
È
[41] Zsolnai L, Huttner G (1994) ZORTEP, University of Heidelberg
[42] CERIUS 2, version 3.0 (1997) Molecular Simulations Inc., San Diego
Received March 20, 1998. Accepted (revised) May 14, 1998