Partial synthesis of C-ring derivatives from oleanolic and maslinic acids. Formation of several triene systems by chemical and photochemical isomerization processes

Article abstract of DOI:10.1016/j.tet.2003.12.023

Some triterpenic compounds modified in C-ring were semi-synthesised from oleanolic acid contained in the solid waste of olive-oil pressing. The corresponding esters of oleanolic and maslinic acids rendered products with a diene system, which led to oleantrienes resembling previtamin D₂ by an electrocyclic reaction. Chemical and photochemical isomerization of these compounds yielded two different trienes with similar structure to tachysterol and vitamin D₂.

Full text of DOI:10.1016/j.tet.2003.12.023

Tetrahedron 60 (2004) 1491–1503
Partial synthesis of C-ring derivatives from oleanolic and maslinic
acids. Formation of several triene systems by chemical and
photochemical isomerization processes
*
Andres Garcıa-Granados, Pilar E. Lopez, Enrique Melguizo, Andres Parra and Yolanda Simeo
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Departamento de Quımica Organica, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
Received 16 September 2003; revised 19 November 2003; accepted 9 December 2003
Abstract—Some triterpenic compounds modified in C-ring were semi-synthesised from oleanolic acid contained in the solid waste of olive-
oil pressing. The corresponding esters of oleanolic and maslinic acids rendered products with a diene system, which led to oleantrienes
resembling previtamin D2 by an electrocyclic reaction. Chemical and photochemical isomerization of these compounds yielded two different
trienes with similar structure to tachysterol and vitamin D2.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
5a-reductase, such as prostate disorders, hair growth and
pubertal changes. Likewise, we reported recent preliminary
results about the formation of several trienes in C-ring from
oleanolic and maslinic acids.8
Oleanolic acid (3b-hydroxy-12-oleanen-28-oic acid, 1) and
maslinic acid (2a,3b-dihydroxy-12-oleanen-28-oic acid, 2)
are widespread in plants in the form of free acids or
derivatives such as methyl esters, acetyl-, oxo-, glycosyl-
and other compounds.1These triterpenic acids also appear,
in large amounts, in olive-oil pressing residues, and our
group has developed a procedure for their isolation from
these solid waste that renders a 0.4% in weight of oleanolic
acid and 0.8% of maslinic acid.2 The large amounts of both
products available allow their use as suitable starting
material for the semi-synthesis of other biologically or
chemically remarkable compounds.3 Moreover, these
natural oleanene acids and several closely related deriva-
tives exhibit biological and pharmacological properties,
such as anti-HIV, hepatoprotective, anti-inflammatory,
cytotoxic or antimicrobial activities, which have been
summarised in some reviews.4
In the present paper, above-mentioned trienes and some
other derivatives in C-ring of this starting material are semi-
synthesised and characterised. Thus, ozonolysis of oleanolic
acid (1) yielded lactone 7, the reactivity of which was
studied with the aim of forming a homodiene (product 18),
which was finally semi-synthesised by reduction of
oleanolic acid (1) with LiAlH4 to obtain erythrodiol9 and
subsequent treatment with NBS. On the other hand, the
reaction of methyl oleanate, methyl maslinate and their
acetyl derivatives with NBS led to dienes 20–23 and some
brominated and rearranged products. We also described the
method of obtaining trienes 30–33 with similar structure to
preergocalciferol (previtamin D2) by a photochemical
reaction starting from the aforementioned dienes. A
chemical isomerization of these compounds with iodine
gave trienes 34–37 (similar in structure to tachysterol) and a
photochemical reaction rendered exocyclic trienes 38–41,
resembling ergocalciferol (vitamin D2). These processes
were based on photochemical interconversions of pro-
vitamin D2, lumisterol, previtamin D2, tachysterol and some
derivatives,10 in addition to photochemical and thermal
transformations of some pentacyclic triterpenoids such as
methyl dehidroursolate.11
In previous papers, we have described the semi-synthesis of
several triterpenic derivatives with the A-ring functional-
ized from oleanolic and maslinic acids.5 In this way,
contracted A-ring, deoxygenated and halohydrins deriva-
tives, aside from a synthon of A, B-rings of Finasteridew
[5a,17b-N-(1,1-dimethylethyl)-3-oxo-4-azaandrostan-1-
ene-17-carboxamide],6 were obtained.7 Finasteridew
belongs to the 4-azasteroid structural class of compounds
and is being used in the treatment of disorders caused by an
excessive production of dihydrotestosterone by the enzyme
2. Results and discussion
Keywords: Oleanolic; Maslinic; Triterpene; Diene; Triene; Isomerization.
*
Oleanolic (1) and maslinic (2) acids were obtained from
olive-pressing residues by successive extractions with
Corresponding author. Tel.: þ34-58-240480; fax: þ34-58-243364;
e-mail address: aparra@ugr.es
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.023

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1492
keto lactone 10. To produce a bromination in a-position to
the carbonyl group, we treated product 10 with a solution of
Br2 in CCl4, rendering compound 11. The stereochemistry
of the halogen atom was established by comparison of the
experimental coupling constant between H-9 and H-11 and
the theoretical values for the two possible dispositions
for H-11. To form a double bond in C-9/C-11, we treated
product 11 with Li2CO3 and LiBr, obtaining the a,b-un-
saturated ketone 12. Searching to form a diene system in
C-ring of triterpene, we opened the lactonic group between
C-13 and C-17 by reduction with LiAlH4, yielding tetrol
13 (Scheme 1). In this product, the stereochemistry of the
hydroxyl group at C-12 was b, since the hydride ion should
enter from the less hindered face, the a face, giving rise to
an hydroxyl group in b.
Figure 1. Structures of products 1–6.
hexane and ethyl acetate in soxhlet.2 The hexane extract
contained mostly oleanolic acid (1) (80–85%), whereas
the EtOAc extract contained mostly maslinic acid (2)
(80–85%). After flash chromatography on a silica gel
column, large amounts of these starting materials were
obtained. The structures of the two oleanene acids (1 and 2)
were established from their spectroscopic data, which were
compared with those in earlier reports.1 Subsequently, we
carried out the esterification of both acids with an ethereal
solution of diazomethane or NaOH–MeI, yielding the
corresponding methyl alcohol esters, compounds 3 and 4.
Acetylation of these esters with Ac2O/Py at reflux provided
acetylated derivatives 5 and 6 (Fig. 1).
On the other hand, to avoid lactonization, we reduced
oleanolic acid (1) with LiAlH4 to give product 14, which
was identified as erythrodiol from their NMR data (Scheme
2).9 Bromination of this compound at C-11 and subsequent
dehydrohalogenation could lead to the diene sought.
However, treatment of this product with NBS gave
compound 15, resulting from the cyclation of the hydroxyl
group at C-28 on C-13 and reaction of negatively charged
C-12 with NBS. To avoid the formation of this cyclic ether,
we protected the hydroxyl group at C-28. Thus, product
14 was acetylated with Ac2O/Py, yielding compounds 16
and 17. The major product of this process, 16, was the
corresponding diacetylated derivative and the minor product
had a cyclic ether between C-28 and C-13 and a double bond
in C-11/C-12 as a consequence of the cyclation of the
hydroxyl group at C-28 before acetylation. Finally, treat-
ment of product 16 with NBS gave diene 18 in one step by
bromination in allylic position and subsequent spontaneous
dehydrohalogenation, and a minor product, 19, which is
another diene with different positions for the double bonds.
Ozonolysis of oleanolic acid (1) in CHCl3:MeOH (1:1) at
278 8C gave lactone 7 (Scheme 1), which was formed by
attack of the carboxylic group at C-28 on C-13 and opening
of the a-epoxide previously formed by the ozonolysis
process between C-12 and C-13. This reaction was similar
to the photochemical lactonization of oleanolic acid
reported by Misra and Laatsch.12 Controlled acetylation of
product 7 at 0 8C provided compounds 8 and 9, acetylated in
different positions of the molecule. The main product of this
reaction, 8 was oxidized with Jones’ reagent to obtain the
According to the above-described results, in order to avoid
the reduction of oleanolic acid and the formation of cyclic
ethers or lactones, and to improve the yield of diene, we
Scheme 1. Reagents and conditions: (a) O3/CHCl3:MeOH/278 8C/30 min 7 (70%); (b) Ac2O/Py/0 8C/3 h 8 (70%) and 9 (20%); (c) Jones’ reagent/0 8C/1 h 10
(95%); (d) Br2/CCl4/rt/5 h 11 (80%); (e) Li2CO3/LiBr/reflux/3 h 12 (60%); (f) LiAlH4/THF/reflux/1.5 h 13 (95%).

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Scheme 2. Reagents and conditions: (a) LiAlH4/THF/reflux/3.5 h 14 (95%); (b) NBS/AIBN/CCl4/rt/1 h 15 (50%); (c) Ac2O/Py/reflux/1.5 h 16 (70%) and 17
(20%); (d) NBS/AIBN/CCl4/rt/1 h 18 (40%) and 19 (5%).
Scheme 3. Reagents and conditions: (a) starting from 3, NBS/AIBN/CCl4/rt/2 h 20 (70%), 24 (10%), 26 (5%) and 28 (10%); starting from 4, NBS/AIBN/CCl4/
reflux/1 h 21 (90%); starting from 5, NBS/AIBN/CCl4/rt/2 h 22 (60%), 25 (15%), 27 (5%) and 29 (15%); starting from 6, NBS/AIBN/CCl4/reflux/1 h 23
(90%).

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Scheme 4. Proposed mechanisms for the obtention of products 20–29.
used methyl oleanate (3), methyl maslinate (4) and their
acetylated derivatives 5 and 6 as starting material for the
diene system formation. Thus, treatment of maslinic esters 4
and 6 with NBS at reflux for 1 h rendered an excellent yield
of dienes 21 and 23 (90%; Scheme 3). Again, a bromination/
dehydrobromination process between C-9 and C-11 had
occurred, giving rise to a conjugated double bond in the
C-ring of the triterpenic compounds (Scheme 4, path a).
However, the reaction of oleanolic esters 3 and 5 with
this reagent at rt for 2 h gave dienes 20 and 2213, and
compounds 24 and 25, 26 and 27, and 28 and 29 (Scheme 3),
which were characterized by their spectroscopic properties.
Products 24 and 25 presented a taraxerene structure and
were formed by the loss of a hydrogen of C-15, migration
of the methyl group at C-14 to C-13 with the same
configuration, and the entry of a halogen atom in C-12
(Scheme 4, path b). This change of skeleton was studied
by Corey et al. from a mixture of a-amiryn and
b-amiryn.14 The taraxerene skeleton is more unstable
than the olean-12-ene (methyl oleanate) system, and the
halogenation in C-12 must provide the required energy to
change the skeleton.
Scheme 5. Reagents and conditions: (a) hn/EtOH/borosilicate flask/20 min 30, 31, 32 and 33 (95%); (b) I2/hexane/reflux/5 h 34, 35, 36 and 37 (60%); (c) hn/
EtOH/quartz flask/30 min 38, 39, 40 and 41 (95%); (d) starting from 41, hn/EtOH/quartz flask/30 min 42 (50%).

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Moreover, starting from compounds 24 and 25, a rearrange-
ment process took place. This transformation could occur
due to the transperiplanar disposition of bonds C-12/Br and
C-13/C-14, leading to products 26 and 27, which presented
a five-membered ring C and a seven-membered ring D
(Scheme 4). The structure of these compounds was
established by their spectroscopic characteristics. The
iodine in hexane in acceptable yield (60%) (Scheme 5). The
trans-disposition of the double bond between C-11 and
C-12 was verified mainly by comparison of H NMR and
1
13C NMR data. Thus, compounds 30–33 (cis-trienes) had
moderately high coupling constants (Table 1). However,
compounds 34–37 (trans-trienes) presented similar shifts
for H-11 and H-12, but had higher coupling constants
between these two protons. Furthermore, products 34–37
had lower 13C NMR shifts for C-11 and C-12 than
compounds 30–33.
1
appearance of two ethylenic protons each coupled in H
NMR spectrum, which correlated with the signals of C-12
and C-18 in HMBC spectrum, supports the proposed
structure.
Finally, by a double bromination/dehydrobromination
process in allylic position and the addition of a halogen
atom in C-12, products 28–29 were formed (Scheme 4, path
c). The presence of four ethylenic quaternary carbon atoms
in 13C NMR spectrum confirmed this structure and the low
shift for C-12 indicated that the halogen atom was situated
in this position.
On the other hand, irradiation of homodienes 20–23 with a
high pressure Hg street lamp in a borosilicate flask yielded
trienes 30–33 (95%), respectively (Scheme 5). This C-ring
opening occurred by a conrotatory photochemical electro-
cyclic reaction similar to the transformation of ergosterol in
previtamin D. This process could take place due to the
trans-disposition between Me on C-8 (C-26) and Me on
C-14 (C-27), that allowed an antarafacial reaction of the 6p
electron system, giving rise to the cleavage of C-8/C-14
bond and thus rendered trienes 30–33 (Scheme 6). The
structure of compound 33 was established by their mono-
and bidimensional spectra and an X-ray experience, that
showed an helicolidal disposition of D, E-rings over A,
B-rings.
Scheme 7. Possible [1,5]H and [1,7]H displacements for products 30–33.
Hypothetically, although the trans disposition of the central
double bond was fixed, there were four possible stereo-
chemical dispositions for the double bonds between C-9 and
C-11 or C-12 and C-13 due to the possible rotation around
these bonds. However, it was verified experimentally that
mainly one product was obtained. Data from NOE
experiments confirmed that one of the ethylenic protons
(H-11 or H-12) was located between the two allylic methyl
groups (Fig. 2). Therefore, we discarded cis–cis and trans–
trans dispositions, since in these structures each ethylenic
proton correlated with only one allylic methyl group.
Finally, to distinguish between the cis–trans (I) or trans–
cis (II) disposition, we examined the results of HMBC and
HMQC experiments. These spectra showed that the
ethylenic proton located between the two allylic methyls
in NOE spectrum correlated in the HMBC spectrum with
C-18, leading us to deduce that this ethylenic hydrogen was
H-12 and products 34–37 presented a cis–trans structure.
Therefore, trans trienes had a S9,11Z S12,13E disposition
(Fig. 3).
Scheme 6. Electrocyclic reaction of products 20–23.
After separation by column chromatography, purification
and characterization, products 30–33 were independently
treated with different oxidative reagents (ozone, OsO4/
NaIO4, RuCl3/NaIO4), rendering a mixture of various epoxy
or methylketone compounds resulting from oxidation in
the most substituted double bonds while the central double
bond (C-11/C-12 double bond) remained unaltered. Subse-
quently, we carried out the chemical isomerization of
cis-trienes 30–33 to trans-trienes 34–37 by treatment with
Table 1. Comparison of some remarkable shifts of products 30–37
30
31
32
33
34
35
36
37
J
11/12 (Hz)
12.9 12.8 12.9 12.6 16.2 16.2 16.2 16.0
C-11 (ppm) 127.3 126.8 127.3 127.2 123.2 122.7 123.0 122.4
C-12 (ppm) 132.9 133.1 132.9 133.3 131.3 131.8 131.4 131.7
Figure 2. Two possible dispositions for products 34–37.

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while a chemical isomerization led to a trans-triene, whose
stereochemical disposition was determined accurately.
These triene products will be used in future research as
starting material for the semi-synthesis of significant
sesquiterpene chiral synthons by cleavage of the central
double bonds.
4. Experimental
4.1. General
Measurements of NMR spectra (300.13 MHz 1H and
75.47 MHz 13C) were made in CDCl3 (which also provided
the lock signal) using BRUKER AM-300 or ARX-400
spectrometers. The assignments of 13C chemical shifts were
made with the aid of distortionless enhancement by
polarization transfer (DEPT) using a flip angle of 1358.
Bruker’s programs were used for COSY (458) and C/H and
C/C correlation. IR spectra were recorded on a MATTSON
SATELLITE FTIR spectrometer. High-resolution mass
spectra were made in a MICROMASS AUTOSPEC-Q
spectrometer (EBE geometry). Mps were determined using
a Kofler (Reichter) apparatus and are uncorrected. Optical
rotations were measured on a Perkin–Elmer 241 polari-
meter at 25 8C. All reaction solvents were dried and distilled
immediately prior to use; chromatography solvents were
distilled prior to use. Commercially available reagents were
used without further purification. Silica gel Scharlau 60
(40–60 mm) was used for flash chromatography. CH2Cl2 or
CHCl3 containing increasing amounts of Me2CO were used
as eluents. Analytical plates (silica gel, Merck 60 G) were
rendered visible by spraying with H2SO4–AcOH, followed
by heating to 120 8C.
Figure 3. Structures of products 34–37.
Moreover, irradiation of products 30–33 (cis-trienes)
independently in a quartz flask for 30 min yielded exocyclic
trienes 38–41 in very high yield (95%) (Scheme 5). The
appearance of an exocyclic double bond was confirmed by
the spectroscopic characteristic of the methylene group.
This product was formed by a [1,5]H displacement, since a
suprafacial migration of one hydrogen from C-26 methyl
group to C-12 took place (Scheme 7). However, a
spontaneous or photochemical [1,7]H sigmatropic
rearrangement did not occur as in the transformation of
provitamin D2 to vitamin D2,10,15 because C-26 and C-27
methyls in trienes 30–33 distorted the molecular confor-
mation, impeding any antarafacial or suprafacial migration
between 1 and 7 positions of the H sigmatropic shift.
Thus, the molecular disposition allowed only one of the two
possible [1,5]H displacements, since experimentally only
trienes 38–41, which presented two conjugated double
bonds between C-8/C-26 and C-9/C-11 and another isolated
double bond between C-13 and C-14 atoms, were formed.
Finally, when exocyclic triene 41 was isolated and
irradiated again under the same conditions for an extra
time of 30 min, product 42 was obtained (Scheme 5).
Analogous compounds to diene 42 were described as over-
irradiation products by Barton et al. in the photochemical
reaction of a triene obtained from methyl dehydroursolate
acetate.11 This compound 42 could be formed by an
electrocyclic reaction of a 4p electron system, giving rise
to a C-26/C-11 bond and a double bond between C-8 and
C-9. The structure was deduced from spectroscopic data,
which showed four ethylenic quaternary carbon atoms and
no methylene group.
4.2. Isolation of starting materials
Oleanolic acid (1)1,2 and maslinic acid (2)1,2 were isolated
from solid wastes resulting from olive-oil production, which
were extracted in a Soxhlet with hexane and EtOAc
successively. Hexane extracts were a mixture of oleanolic
acid and maslinic acid (80:20) whereas this relationship was
(20:80) for the EtOAc extracts. Both products were purified
from these mixtures by column chromatography over silica
gel, eluting with a CHCl3–MeOH or CH2Cl2–Acetone
mixtures of increasing polarity. Oleanolic acid (1) and
maslinic acid (2) were transformed into the corresponding
methyl esters with ethereal CH2N2 or NaOH–MeI and thus,
methyl 3b-hydroxy-12-oleanen-28-oate (3)5 and methyl
2a,3b-dihydroxy-12-oleanen-28-oate (4)5 were obtained.
Acetylation of these esters with Ac2O/Py at reflux provided
acetylated derivatives 55 and 65.
3. Conclusion
Oleanolic and maslinic acids were suitable starting material
for the semi-synthesis of several remarkable derivatives
modified in C and/or D rings of the oleanene skeleton.
Treatment of the esters of aforementioned acids with NBS
gave rise to a promising diene system in C-ring by a
spontaneous bromination/dehydrobromination process.
4.2.1. Ozonolysis of 1. Product 1 (1.5 g, 3.3 mmol), after
being dissolved in 15 mL of CHCl3 and 15 mL of MeOH,
was stirred at 278 8C and passed through an O3 flow of
0.1 L/min (10% O2–90% O3). After 30 min, excess ozone
was removed with argon. The mixture was maintained with
stirring while being cooled down for 4 h. Then it was
evaporated and purified over silica gel, yielding 1.08 g
(70%) of 7: white solid; mp 247–249 8C; [a]2D5¼26 (c 1,
The cleveage of the C-8/C-14 bond of the diene by an
electrocyclic reaction was achieved, yielding a triene with
the C-ring opened. Starting from this compound, an
exocyclic triene was obtained by a photochemical reaction,
1
CHCl3); IR (CHCl3): n 3472, 2949, 1751 cm21; H NMR
(CDCl3): d 3.87 (1H, dd, J1¼J2¼2.9 Hz, H-12), 3.21 (1H,

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1497
dd, J1¼5.4 Hz, J2¼10.9 Hz, H-3), 1.29 (3H, s, 3H-27), 1.13
(3H, s, 3H-26), 0.98 (3H, s, 3H-23), 0.97 (3H, s, 3H-29),
0.88 (3H, s, 3H-30), 0.86 (3H, s, 3H-25), 0.76 (3H, s,
3H-24); 13C NMR (CDCl3): d 15.4 (C-24), 16.4 (C-25), 17.8
(C-6), 18.6 and 18.7 (C-26 and C-27), 21.3 (C-16), 24.0
(C-30), 27.3, 27.5, 28.1 and 28.8 (C-2, C-11, C-15 and
C-22), 28.1 (C-23), 31.6 (C-20), 33.3 (C-29), 34.0 and 34.2
(C-7 and C-21), 36.5 (C-10), 38.9 (C-1), 39.0 (C-4), 39.5
(C-19), 42.1 (C-14), 42.4 (C-8), 44.6 (C-9), 44.8 (C-17),
51.2 (C-18), 55.2 (C-5), 76.4 (C-12), 78.9 (C-3), 90.7
(C-13), 180.0 (C-28); HRLSIMS, m/z: [MþNa]þ 495.3454
(C30H48O4Na, calcd 495.3450).
1H NMR (CDCl3): d 4.46 (1H, dd, J1¼5.0 Hz, J2¼10.8 Hz,
H-3), 2.69 (1H, dd, J1¼J2¼13.9 Hz, H-11a), 2.52 (1H, dd,
J1¼J2¼8.2 Hz, H-18), 2.35 (1H, dd, J1¼3.0 Hz, J2¼
13.9 Hz, H-11b), 2.03 (3H, s, COCH3), 1.30 (3H, s,
3H-25), 0.96 (3H, s, 3H-29), 0.94 (3H, s, 3H-26), 0.94
(3H, s, 3H-27), 0.92 (3H, s, 3H-23), 0.85 (3H, s, 3H-30),
0.85 (3H, s, 3H-24); 13C NMR (CDCl3): d 15.9 and 18.2
(C-26 and C-27), 16.4 (C-24), 17.5 (C-6), 18.6 (C-25), 20.7
(C-16), 21.3 (COCH3), 23.4 (C-2), 23.8 (C-30), 25.9 (C-15),
27.3 (C-22), 27.9 (C-23), 31.6 (C-20), 32.9 (C-1), 33.2
(C-29), 34.2 (C-7), 37.2 and 37.9 (C-4 and C-10), 37.3 and
37.4 (C-11 and C-21), 38.1 (C-19), 42.5 (C-8), 43.7 (C-14),
44.0 (C-18), 44.0 (C-17), 51.0 (C-9), 55.0 (C-5), 80.3 (C-3),
91.0 (C-13), 171.0 (COCH3), 178.5 (C-28), 206.0 (C-12);
HRLSIMS, m/z: [MþNa]þ 535.3391 (C32H48O5Na, calcd
535.3399).
4.2.2. Acetylation of 7. Product 7 (650 mg, 1.4 mmol) was
dissolved in 20 mL of pyridine and 10 mL of Ac2O and
stirred for 3 h at 0 8C. The reaction mixture was diluted
with water, extracted with CH2Cl2, washed with saturated
aqueous KHSO4 solution and dried with anhydrous Na2SO4.
The solvent was evaporated at reduced pressure and the
residue was chromatographed on a silica gel column to give
65 mg (10%) of 7, 495 mg (70%) of product 8: white solid;
mp 261–263 8C; [a]D25¼37 (c 1, CHCl3); IR (CHCl3): n
4.2.4. Treatment of 10 with bromine. Product 10 (405 mg,
0.8 mmol) was dissolved in 10 mL of CH2Cl2 and 4 mL of a
0.1 M solution of Br2 in CCl4 were added.The reaction
mixture was maintained at room temperature for 5 h, and
then diluted with CH2Cl2, neutralized with a NaHCO3
solution, dried over anhydrous Na2SO4 and evaporated to
dryness. Chromatography over silica gel yielded 374 mg
(80%) of 11: white solid; mp 252–254 8C; [a]2D5¼4 (c 1,
1
3487, 2928, 2360, 1739, 1247 cm21; H NMR (CDCl3): d
4.48 (1H, dd, J1¼5.7 Hz, J2¼9.7 Hz, H-3), 3.87 (1H, dd,
J1¼J2¼2.5 Hz, H-12), 2.04 (3H, s, COCH3), 1.29 (3H, s,
Me), 1.13 (3H, s, Me), 0.97 (3H, s, Me), 0.89 (3H, s, Me),
0.89 (3H, s, Me), 0.86 (3H, s, Me), 0.84 (3H, s, Me); 13C
NMR (CDCl3): d 16.5 (C-24), 16.5 (C-25), 17.7 (C-6), 18.6
and 18.7 (C-26 and C-27), 21.3 (C-16), 21.4 (COCH3), 23.6
(C-2), 24.0 (C-30), 27.6, 28.1 and 28.9 (C-11, C-15 and
C-22), 28.0 (C-23), 31.6 (C-20), 33.3 (C-29), 34.0 and 34.2
(C-7 and C-21), 36.4 (C-10), 37.9 (C-4), 38.6 and 39.4 (C-1
and C-19), 42.1 (C-14), 42.4 (C-8), 44.6 (C-9), 44.8 (C-17),
51.2 (C-18), 55.4 (C-5), 76.3 (C-12), 80.9 (C-3), 90.7
(C-13), 171.2 (COCH3), 180.1 (C-28); HRLSIMS, m/z:
[MþNa]þ 537.3557 (C32H50O5Na, calcd 537.3556); and
150 mg (20%) of 9: white solid; mp 241–243 8C; [a]2D5¼57
(c 1, CHCl3); IR (CHCl3): n 2928, 2360, 1776, 1743,
1
CHCl3); IR (CHCl3): n 2949, 1780, 1719, 1247 cm21; H
NMR (CDCl3): d 4.47 (1H, dd, J1¼4.5 Hz, J2¼11.1 Hz,
H-3), 4.32 (1H, d, J¼6.6 Hz, H-11), 2.67 (1H, dd, J1¼
2.7 Hz, J2¼13.7 Hz, H-18), 2.03 (3H, s, COCH3), 1.46 (3H,
s, Me), 0.98 (3H, s, Me), 0.97 (3H, s, Me), 0.90 (3H, s, Me),
0.87 (3H, s, Me), 0.85 (3H, s, Me), 0.84 (3H, s, Me); 13C
NMR (CDCl3): d 16.3 (Me), 16.7 (Me), 17.3 (C-6), 19.4
(Me), 20.3 (Me), 21.3 (COCH3), 21.5 (C-16), 23.4 (C-2),
23.5 (C-30), 26.5 and 26.8 (C-15 and C-22), 27.8 (C-23),
31.5 (C-1), 31.7 (C-20), 33.3 (C-29), 34.3 (C-7), 37.1
(C-21), 38.0 (C-4), 39.0 (C-19), 39.1 (C-10), 41.7 and 42.2
(C-8 and C-14), 44.6 (C-17), 46.1 and 48.4 (C-9 and C-18),
55.1 (C-5), 57.4 (C-11), 80.1 (C-3), 90.6 (C-13), 171.0
(COCH3), 177.7 (C-28), 200.3 (C-12); HRLSIMS, m/z:
[MþNa]þ 613.2510 (C32H47O5BrNa, calcd 613.2505).
1
1246 cm21; H NMR (CDCl3): d 5.01 (1H, dd, J1¼J2¼
2.9 Hz, H-12), 4.47 (1H, dd, J1¼6.2 Hz, J2¼10.0 Hz, H-3),
2.09 (3H, s, COCH3), 2.04 (3H, s, COCH3), 1.26 (3H, s,
Me), 1.15 (3H, s, Me), 0.96 (3H, s, Me), 0.87 (3H, s, Me),
0.86 (3H, s, Me), 0.84 (3H, s, Me), 0.81 (3H, s, Me); 13C
NMR (CDCl3): d 16.3 and 16.5 (C-24 and C-25), 17.7 (C-6),
18.4 and 18.6 (C-26 and C-27), 21.1 (C-16), 21.4 (COCH3),
21.5 (COCH3), 23.6 (C-2), 23.9 (C-30), 25.2 (C-15), 27.4
and 27.9 (C-11 and C-22), 28.0 (C-23), 31.6 (C-20), 33.4
(C-29), 33.9 (C-7), 33.9 (C-21), 36.4 (C-10), 37.9 (C-4),
38.5 (C-1), 39.5 (C-19), 42.2 (C-14), 42.3 (C-8), 44.6
(C-17), 45.4 (C-9), 50.3 (C-18), 55.4 (C-5), 76.8 (C-12),
80.7 (C-3), 89.5 (C-13), 169.4 (COCH3), 171.2 (COCH3),
179.1 (C-28); HRLSIMS, m/z: [MþNa]þ 579.3664
(C34H52O6Na, calcd 579.3662).
4.2.5. Dehydrohalogenation of 11. Product 11 (318 mg,
0.5 mmol) was dissolved in 10 mL of anhydrous DMF, and
LiBr (116 mg, 1.3 mmol) and Li2CO3 (155 mg, 2.1 mmol)
were added. After 3 h at reflux, the reaction mixture was
extracted with an acetic acid solution and CH2Cl2,
neutralized with NaHCO3, dried over anhydrous Na2SO4,
evaporated to dryness and chromatographed on a silica gel
column to obtain 95 mg (30%) of 11 and 166 mg (60%) of
12: white solid; mp 274–276 8C; [a]2D5¼74 (c 1, CHCl3); IR
1
(CHCl3): n 2951, 1778, 1735, 1667, 1246 cm21; H NMR
(CDCl3): d 5.97 (1H, s, H-11), 4.47 (1H, dd, J1¼5.0 Hz,
J2¼11.3 Hz, H-3), 2.94 (1H, dd, J1¼2.7 Hz, J2¼13.5 Hz,
H-18), 2.06 (3H, s, COCH3), 1.44 (3H, s, Me), 1.27 (3H, s,
Me), 0.98 (3H, s, Me), 0.95 (3H, s, Me), 0.95 (3H, s, Me),
0.92 (3H, s, Me), 0.90 (3H, s, Me); 13C NMR (CDCl3): d
16.7 (Me), 17.2 (C-6), 20.3 (C-16), 21.3 (COCH3), 23.1
(Me), 23.9 (C-2), 23.9 (Me), 24.5 (Me), 25.9 (C-15), 27.2
(C-22), 28.1 (Me), 30.1 (Me), 31.7 (C-20), 33.2 (C-29), 34.0
and 34.1 (C-1 and C-7), 36.1 and 36.7 (C-19 and C-21), 38.3
(C-4), 40.3 (C-10), 41.7 (C-8), 43.6 (C-14), 44.0 (C-18),
46.0 (C-17), 50.4 (C-5), 79.6 (C-3), 87.9 (C-13), 121.8
(C-11), 171.0 (COCH3), 178.8 (C-28), 183.6 (C-9), 192.4
4.2.3. Oxidation of 8. Jones’ reagent was added dropwise
to a stirred solution of product 8 (450 mg, 0.9 mmol) in
acetone at 0 8C until an orange-brown colour persisted.
Methanol was added and the reaction mixture was diluted
with water and extracted with CH2Cl2. The organic layer
was dried over anhydrous Na2SO4, evaporated to dryness
and chromatographed on a silica gel column to obtain
425 mg (95%) of 10: white solid; mp 287–289 8C; [a]2D5¼8
(c 1, CHCl3); IR (CHCl3): n 2951, 1780, 1727, 1247 cm21
;

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A. Garcıa-Granados et al. / Tetrahedron 60 (2004) 1491–1503
1498
(C-12); HRLSIMS, m/z: [MþNa]þ 533.3249 (C32H46O5Na,
residue was chromatographed on a silica gel column to give
111 mg (70%) of 16: white solid; mp 168–170 8C; [a]2D5¼
56 (c 1, CHCl3); IR (CHCl3): n 2948, 1737, 1245 cm21; 1H
NMR (CDCl3): d 5.18 (1H, dd, J1¼J2¼3.6 Hz, H-12), 4.48
(1H, dd, J1¼7.3 Hz, J2¼9.1 Hz, H-3), 4.01 (1H, d, J¼
11.0 Hz, H-28a), 3.68 (1H, d, J¼11.0 Hz, H-28b), 2.03 (3H,
s, COOCH3), 2.03 (3H, s, COOCH3), 1.14 (3H, s, Me), 0.93
(3H, s, Me), 0.93 (3H, s, Me), 0.87 (3H, s, Me), 0.85 (3H, s,
Me), 0.85 (3H, s, Me), 0.84 (3H, s, Me); 13C NMR (CDCl3):
d 15.6 (C-26), 16.7 (C-24), 16.7 (C-25), 18.3 (C-6), 21.0
(COCH3), 21.4 (COCH3), 21.4 (C-30), 22.3 (C-16), 23.6
(C-2), 23.6 (C-11), 25.6 (C-15), 26.0 (C-27), 28.1 (C-23),
30.9 (C-20), 31.4 (C-22), 32.5 (C-7), 33.2 (C-29), 34.0
(C-21), 35.8, 36.9, 37.8 and 39.8 (C-4, C-8, C-10 and C-17),
38.3 (C-1), 41.7 (C-14), 42.6 (C-18), 46.3 (C-19), 47.6
(C-9), 55.3 (C-5), 70.8 (C-28), 80.9 (C-3), 122.9 (C-12),
143.7 (C-13), 171.1 (COCH3), 171.4 (COCH3); HRLSIMS,
m/z: [MþNa]þ 549.3913 (C34H54O4Na, calcd 549.3920);
and 29 mg (20%) of 17: white solid; mp 205–207 8C;
[a]2D5¼74 (c 1, CHCl3); IR (CHCl3): n 2925, 1737,
calcd 533.3243).
4.2.6. Reduction of 12. 140 mg (0.3 mmol) of product 12
were dissolved in 2 mL of dry THF and 1 mL of a solution
of LiAlH4 in THF (1 M) was added. The reaction mixture
was maintained at reflux for 1.5 h, and then diluted with
aqueous ether, extracted with CH2Cl2, dried over anhydrous
Na2SO4 and evaporated to dryness. Chromatography
over silica gel yielded 124 mg (95%) of 13: white solid;
mp 233–235 8C; [a]D25¼23 (c 1, CHCl3); IR (CHCl3): n
1
3371, 2938 cm21; H NMR (CDCl3): d 5.25 (1H, d, J¼
2.3 Hz, H-11), 4.24 (1H, d, J¼2.3 Hz, H-12), 3.93 (1H, d,
J¼10.9 Hz, H-28a), 3.42 (1H, d, J¼10.9 Hz, H-28b), 3.17
(1H, dd, J1¼4.8 Hz, J2¼11.3 Hz, H-3), 1.42 (3H, s, Me),
1.17 (3H, s, Me), 1.02 (3H, s, Me), 0.97 (3H, s, Me), 0.89
(3H, s, Me), 0.89 (3H, s, Me), 0.80 (3H, s, Me); 13C NMR
(CDCl3): d 15.5 (Me), 18.0 (C-6), 22.3 (Me), 24.1 (Me),
24.4 (Me), 25.5 (Me), 26.1 (C-15), 26.1 (C-16), 27.9 (C-2),
28.1 (Me), 31.2 (C-20), 32.7 (C-29), 33.2, 34.0 and 34.3
(C-7, C-21 and C-22), 36.7 and 39.4 (C-4 and C-10), 38.2
(C-1), 39.8 (C-18), 39.9 (C-8), 40.1 (C-19), 44.1 (C-14),
44.5 (C-17), 53.2 (C-5), 68.5 (C-12), 70.6 (C-28), 77.8
(C-13), 78.5 (C-3), 119.2 (C-11), 154.8 (C-9); HRLSIMS,
m/z: [MþNa]þ 497.3600 (C30H50O4Na, calcd 497.3607).
1
1244 cm21; H NMR (CDCl3): d 5.83 (1H, d, J¼10.3 Hz,
H-12), 5.36 (1H, dd, J1¼3.2 Hz, J2¼10.2 Hz, H-11), 4.47
(1H, dd, J1¼8.3 Hz, J2¼9.2 Hz, H-3), 3.69 (1H, d, J¼
6.7 Hz, H-28a), 3.25 (1H, d, J¼6.7 Hz, H-28b), 2.04 (3H, s,
COCH3), 1.07 (3H, s, Me), 0.95 (3H, s, Me), 0.92 (3H, s,
Me), 0.91 (3H, s, Me), 0.85 (3H, s, Me), 0.84 (3H, s, Me),
0.84 (3H, s, Me); 13C NMR (CDCl3): d 16.1 (Me), 17.6
(C-6), 18.0 (Me), 19.4 (Me), 19.5 (Me), 21.4 (COCH3), 23.5
(C-16), 23.6 (Me), 25.3 and 25.7 (C-2 and C-15), 27.8
(C-27), 30.9 (C-7), 31.3 (C-21), 31.7 (C-20), 33.7 (C-29),
34.9 (C-22), 36.4, 37.9, 41.6, 41.6 and 43.8 (C-4, C-8, C-10,
C-14 and C-17), 37.1 and 38.0 (C-1 and C-19), 51.1 (C-9),
53.2 (C-18), 54.9 (C-5), 77.0 (C-28), 80.9 (C-3), 84.8
(C-13), 131.0 and 132.1 (C-11 and C-12), 171.1 (COCH3);
HRLSIMS, m/z: [MþNa]þ 505.3669 (C32H50O3Na, calcd
505.3658).
4.2.7. Reduction of 1. Product 1 (500 mg, 1.1 mmol) was
dissolved in 20 mL of dry THF and 8 mL of a 1 M solution
of LiAlH4 in THF were added. After 3.5 h at reflux, the
reaction mixture was diluted with aqueous ether, extracted
with CH2Cl2, dried over anhydrous Na2SO4, evaporated to
dryness and chromatographed over silica gel to obtain
478 mg (95%) of product 14.9
4.2.8. Bromination of 14. Product 14 (228 mg, 0.5 mmol)
was dissolved in 15 mL of CCl4, and 90 mg (0.5 mmol) of
NBS and a catalytic amount of AIBN were added. The
reaction mixture was maintained at room temperature for
1 h and then extracted with a solution of NaHCO3, dried
over anhydrous Na2SO4 and evaporated to dryness.
Chromatography over silica gel yielded 113 mg (50%) of
14 and 130 mg (50%) of 15: white solid; mp 124–126 8C;
[a]D25¼78 (c 1, CHCl3); IR (CHCl3): n 3422, 2927 cm21; 1H
NMR (CDCl3): d 4.24 (1H, dd, J1¼2.5 Hz, J2¼3.5 Hz,
H-12), 3.73 (1H, d, J¼7.0 Hz, H-28a), 3.28 (1H, d, J¼
7.0 Hz, H-28b), 3.24 (1H, dd, J1¼4.9 Hz, J2¼11.2 Hz, H-3),
1.30 (3H, s, Me), 1.25 (3H, s, Me), 0.98 (3H, s, Me), 0.97
(3H, s, Me), 0.89 (3H, s, Me), 0.87 (3H, s, Me), 0.76 (3H, s,
Me); 13C NMR (CDCl3): d 15.5 (Me), 17.1 (Me), 17.8 (C-6),
19.3 (Me), 21.8 (Me), 23.7 (Me), 25.0 (C-16), 27.3 (C-2),
28.1 (C-23), 29.2 (C-15), 31.1 (C-7), 31.1 (C-11), 32.0
(C-20), 33.7 (C-29), 34.3 (C-21), 35.0 (C-22), 36.7 (C-4),
38.4 (C-1), 39.0 (C-10), 40.2 (C-19), 42.7 and 43.0 (C-8 and
C-17), 45.7 (C-14), 46.0 (C-9), 53.2 (C-18), 55.3 (C-5), 60.6
(C-12), 77.5 (C-28), 78.9 (C-3), 87.5 (C-13); HRLSIMS,
m/z: [MþNa]þ 543.2812 (C30H49O2BrNa, calcd 543.2814).
4.2.10. Treatment of 16 with NBS. Product 16 (81 mg,
0.15 mmol) was dissolved in 8 mL of CCl4, and 27 mg
(0.15 mmol) of NBS and a catalytic amount of AIBN were
added. The reaction mixture was maintained at room
temperature for 1 h and then extracted with a solution of
NaHCO3, dried over anhydrous Na2SO4 and evaporated to
dryness. Chromatography over silica gel yielded 32 mg
(40%) of 18: syrup; [a]2D5¼210 (c 1, CHCl3); IR (CHCl3): n
1
2948, 1738, 1244 cm21; H NMR (CDCl3): d 5.55 (1H, d,
J¼5.8 Hz, H-11), 5.49 (1H, d, J¼5.8 Hz, H-12), 4.50 (1H,
dd, J1¼5.8 Hz, J2¼10.6 Hz, H-3), 4.06 (1H, d, J¼11.0 Hz,
H-28a), 3.76 (1H, d, J¼11.1 Hz, H-28b), 2.04 (3H, s,
COCH3), 2.04 (3H, s, COCH3), 1.19 (3H, s, 3H-25), 1.11
(3H, s, 3H-26), 0.99 (3H, s, 3H-27), 0.89 (3H, s, 3H-23),
0.89 (3H, s, 3H-30), 0.88 (3H, s, 3H-24), 0.86 (3H, s,
3H-29); 13C NMR (CDCl3): d 16.8 (C-24), 18.2 (C-6), 20.0
(C-27), 20.9 (COCH3), 21.1 (COCH3), 21.4 (C-26), 22.7
(C-16), 23.6 (C-30), 24.3 (C-2), 25.1 (C-15), 25.3 (C-25),
28.2 (C-23), 31.0 (C-20), 31.4 (C-22), 32.0 (C-7), 33.1
(C-29), 33.9 (C-21), 35.6 (C-17), 36.9 (C-1), 37.9 (C-4),
38.7 (C-10), 40.7 (C-14), 40.9 (C-18), 42.7 (C-8), 46.4
(C-19), 51.2 (C-5), 71.1 (C-28), 80.6 (C-3), 115.9 (C-11),
121.5 (C-12), 145.2 (C-13), 154.5 (C-9), 171.1 (COCH3),
171.4 (COCH3); HRLSIMS, m/z: [MþNa]þ 547.3762
(C34H52O4Na, calcd 547.3763); and 4 mg (5%) of 19:
white solid; mp 139–141 8C; [a]2D5¼26 (c 0.4, CHCl3); IR
4.2.9. Acetylation of 14. Product 14 (138 mg, 0.3 mmol)
was dissolved in 6 mL of pyridine and 3 mL of Ac2O and
stirred for 1.5 h at reflux. The reaction mixture was diluted
with water, extracted with CH2Cl2, washed with saturated
aqueous KHSO4 solution and dried with anhydrous Na2SO4.
The solvent was evaporated at reduced pressure and the

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A. Garcıa-Granados et al. / Tetrahedron 60 (2004) 1491–1503
1499
(CHCl3): n 2929, 1737, 1242 cm21; H NMR (CDCl3): d
6.39 (1H, dd, J1¼3.1 Hz, J2¼10.6 Hz, H-11), 5.57 (1H, d,
J¼10.6 Hz, H-12), 4.50 (1H, dd, J1¼6.2 Hz, J2¼10.0 Hz,
H-3), 4.16 (1H, d, J¼11.2 Hz, H-28a), 3.98 (1H, d,
J¼11.2 Hz, H-28b), 2.05 (3H, s, COCH3), 2.04 (3H, s,
COCH3), 0.95 (3H, s, Me), 0.94 (3H, s, Me), 0.91 (3H, s,
Me), 0.85 (3H, s, Me), 0.84 (3H, s, Me), 0.77 (3H, s, Me),
0.71 (3H, s, Me); 13C NMR (CDCl3): d 16.2 (Me), 16.7
(Me), 18.1 (Me), 18.3 (C-6), 20.4 (Me), 21.2 (COCH3), 21.4
(COCH3), 23.5 and 24.3 (C-2 and C-15), 24.4 (Me), 27.9
(C-23), 30.0 (C-16), 32.3 (C-29), 32.4, 33.0 and 35.0 (C-7,
C-21 and C-22), 33.0 (C-20), 36.7, 37.9 and 38.0 (C-4, C-8
and C-10), 37.8 and 38.2 (C-1 and C-19), 40.4 and 42.3 (C-
14 and C-17), 54.2 (C-9), 55.0 (C-5), 65.8 (C-28), 80.9 (C-
3), 125.5 and 126.6 (C-11 and C-12), 133.2 and 137.1 (C-13
and C-18), 171.1 (COCH3), 171.4 (COCH3); HRLSIMS,
m/z: [MþNa]þ 547.3764 (C34H52O4Na, calcd 547.3763).
12), 3.30 (1H, dd, J1¼2.4 Hz, J2¼12.5 Hz, H-18), 3.17 (1H,
dd, J1¼6.5 Hz, J2¼9.2 Hz, H-3), 2.17 (1H, dd, J1¼2.2 Hz,
J2¼4.7 Hz, H-16), 0.95 (3H, s, 3H-23), 0.95 (3H, s, 3H-29),
0.93 (3H, s, 3H-26), 0.86 (3H, s, 3H-30), 0.83 (3H, s, 3H-
25), 0.78 (3H, s, 3H-24); 13C NMR (CDCl3): d 15.3 and 15.4
(C-24 and C-25), 19.1 (C-6), 22.3 (C-30), 27.1 and 27.2 (C-
2 and C-7), 27.5 and 28.2 (C-23 and C-29), 29.7 (C-20),
31.9 (C-26), 31.9 (C-16), 33.6 and 34.7 (C-21 and C-22),
36.9 (C-10), 38.1, 38.2 and 38.6 (C-1, C-11 and C-19), 38.9
(C-4), 41.0 (C-18), 42.0 (C-12), 46.2 (C-8), 50.4 (C-17),
51.9 (COOCH3), 56.3 (C-5), 59.7 (C-9), 79.3 (C-3), 105.2
(C-27), 113.0 (C-15), 155.7 (C-13), 157.3 (C-14), 179.9 (C-
28); HRLSIMS, m/z: [MþNa]þ 491.3492 (C31H48O3Na,
calcd 491.3501); and 167 mg (10%) of 28: white solid; mp
148–150 8C; [a]2D5¼83 (c 1, CHCl3); IR (CHCl3): n 3469,
1
1
2949, 1724, 1458, 1217, 1033 cm21; H NMR (CDCl3): d
5.93 (1H, s, H-19), 5.81 (1H, s, H-11), 3.64 (3H, s,
COOCH3), 3.22 (1H, dd, J1¼4.9 Hz, J2¼11.3 Hz, H-3),
1.24 (3H, s, Me), 1.09 (3H, s, Me), 1.06 (3H, s, Me), 1.00
(3H, s, Me), 0.97 (3H, s, Me), 0.88 (3H, s, Me), 0.79 (3H, s,
Me); 13C NMR (CDCl3): d 15.8 (C-24), 16.8 (C-27), 18.2
(C-6), 21.9 (C-26), 25.5 (C-25), 27.0 (C-15), 27.8 (C-2),
28.3 (C-23), 28.3 (C-30), 29.4 (C-29), 32.5 (C-22), 33.3 (C-
7), 33.3 (C-20), 33.5 (C-21), 34.3 (C-16), 37.1 (C-1), 39.0
(C-10), 39.0 (C-4), 42.3 (C-8), 46.0 (C-14), 47.6 (C-17),
51.3 (C-5), 52.1 (COOCH3), 78.5 (C-3), 113.2 (C-12), 123.0
(C-11), 131.6 (C-18), 139.3 (C-13), 141.4 (C-19), 156.5 (C-
9), 177.1 (C-28); HRLSIMS, m/z: [MþNa]þ 567.2447
(C31H45O3BrNa, calcd 567.2450).
4.2.11. Treatment of 3 with NBS. Product 3 (1.4 g,
3 mmol) was dissolved in 30 mL of CCl4, and 535 mg
(3 mmol) of NBS and a catalytic amount of AIBN were
added. After 2 h at room temperature, the reaction mixture
was extracted with a solution of NaHCO3, dried over
anhydrous Na2SO4, evaporated to dryness and chromato-
graphed on a silica gel column to obtain 989 mg (70%) of
20: white solid; mp 133–135 8C; [a]2D5¼258 (c 1, CHCl3);
IR (CHCl3): n 3457, 2947, 1723 cm21; 1H NMR (CDCl3): d
5.57 (1H, d, J¼5.9 Hz, H-11), 5.54 (1H, d, J¼5.9 Hz, H-
12), 3.62 (3H, s, COOCH3), 3.21 (1H, dd, J1¼4.9 Hz,
J2¼11.2 Hz, H-3), 2.99 (1H, dd, J1¼3.7 Hz, J2¼13.2 Hz, H-
18), 1.14 (3H, s, 3H-25), 1.00 (3H, s, 3H-23), 0.99 (3H, s,
3H-27), 0.92 (3H, s, 3H-30), 0.92 (3H, s, 3H-26), 0.88 (3H,
s, 3H-29), 0.78 (3H, s, 3H-24); 13C NMR (CDCl3): d 15.7
(C-24), 18.3 (C-6), 20.2 (C-26), 20.2 (C-27), 23.7 (C-30),
23.8 (C-16), 25.1 (C-25), 27.00 (C-15), 27.9 (C-2), 28.3 (C-
23), 30.7 (C-20), 32.2 (C-7), 32.2 (C-22), 33.0 (C-29), 33.8
(C-21), 37.1 (C-1), 38.9 (C-10), 39.0 (C-4), 39.7 (C-18),
40.7 (C-14), 42.4 (C-8), 45.9 (C-19), 46.1 (C-17), 51.2 (C-
5), 51.8 (COOCH3), 78.7 (C-3), 115.7 (C-11), 120.6 (C-12),
145.2 (C-13), 154.6 (C-9), 178.4 (C-28); HRLSIMS, m/z:
[MþNa]þ 491.3500 (C31H48O3Na, calc. 491.3501); 165 mg
(10%) of 24: white solid; mp 173–175 8C; [a]2D5¼31 (c 1,
4.2.12. Treatment of 4 with NBS. Product 4 (1.2 g,
2.5 mmol) was dissolved in 30 mL of CCl4, and 446 mg
(2.5 mmol) of NBS and a catalytic amount of AIBN were
added. The reaction mixture was maintained at reflux for
1 h, and then extracted with a solution of NaHCO3, dried
over anhydrous Na2SO4, evaporated to dryness and
chromatographed on a silica gel column to obtain 1.1 g
(90%) of 21: white solid; mp 221–223 8C; [a]2D5¼107 (c 1,
1
CHCl3); IR (CHCl3): n 3433, 2946, 1727 cm21; H NMR
(CDCl3): d 5.59 (1H, d, J¼5.8 Hz, H-11), 5.53 (1H, d,
J¼5.8 Hz, H-12), 3.71 (1H, ddd, J1¼4.3 Hz, J2¼9.6 Hz,
J3¼11.6 Hz, H-2), 3.61 (3H, s, COOCH3), 2.98 (1H, d,
J¼9.6 Hz, H-3), 2.29 (1H, dd, J1¼4.4 Hz, J2¼12.5 Hz, H-
18), 1.18 (3H, s, Me), 1.02 (3H, s, Me), 0.97 (3H, s, Me),
0.91 (3H, s, Me), 0.90 (3H, s, Me), 0.86 (3H, s, Me), 0.80
(3H, s, Me); 13C NMR (CDCl3): d 16.9 (Me), 18.3 (C-6),
20.3 (Me), 20.4 (Me), 23.7 (Me), 23.8 (C-16), 26.1 (Me),
26.9 (C-15), 28.8 (Me), 30.7 (C-20), 32.1 (C-7), 32.2 (C-
22), 33.0 (Me), 33.8 (C-21), 39.1 (C-4), 39.7 (C-18), 40.0
(C-8), 40.8 (C-10), 42.3 (C-14), 45.1 (C-1), 45.9 (C-19),
46.1 (C-17), 51.3 (C-5), 51.8 (COOCH3), 69.5 (C-2), 83.6
(C-3), 116.0 (C-11), 120.5 (C-12), 145.5 (C-13), 153.4 (C-
9), 178.4 (C-28); HRLSIMS, m/z: [MþNa]þ 507.3446
(C31H48O4Na, calcd 507.3450).
CHCl3); IR (CHCl3): n 3330, 2945, 1723 cm21; H NMR
1
(CDCl3): d 5.66 (1H, dd, J1¼3.3 Hz, J2¼8.1 Hz, H-15),
4.84 (1H, dd, J1¼J2¼9.4 Hz, H-12), 3.55 (3H, s, COOCH3),
3.17 (1H, dd, J1¼5.2 Hz, J2¼10.8 Hz, H-3), 2.71 (1H, dd,
J1¼6.0 Hz, J2¼13.5 Hz, H-18), 1.07 (3H, s, 3H-27), 0.96
(3H, s, 3H-30), 0.94 (3H, s, 3H-23), 0.91 (3H, s, 3H-29),
0.87 (3H, s, 3H-25), 0.83 (3H, s, 3H-26), 0.75 (3H, s, 3H-
24); 13C NMR (CDCl3): d 15.4 (C-24), 15.7 (C-25), 18.8 (C-
6), 20.7 (C-27), 25.7 (C-30), 27.1 (C-2), 27.6 (C-26), 27.9
(C-23), 29.2 (C-11), 30.9 (C-20), 31.9, 32.4 and 33.9 (C-7,
C-21 and C-22), 32.3 (C-29), 37.1 (C-1), 37.8 (C-10), 37.8
(C-16), 38.8 (C-4), 39.6 (C-8), 41.1 (C-19), 41.4 (C-18),
43.7 (C-13), 51.2 (C-17), 51.4 (C-9), 51.7 (COOCH3), 55.4
(C-5), 66.2 (C-12), 78.8 (C-3), 121.5 (C-15), 157.5 (C-14),
178.2 (C-28); HRLSIMS, m/z: [MþNa]þ 571.2761 (C31-
H49O3BrNa, calcd 571.2763); 75 mg (5%) of 26: white
solid; mp 143–145 8C; [a]2D5¼5 (c 1, CHCl3); IR (CHCl3): n
4.2.13. Treatment of 5 with NBS. Product 5 (1 g, 2 mmol)
was dissolved in 30 mL of CCl4, and 357 mg (2 mmol) of
NBS and a catalytic amount of AIBN were added. After 2 h
at room temperature, the reaction mixture was extracted
with a solution of NaHCO3, dried over anhydrous Na2SO4,
evaporated to dryness and chromatographed on a silica gel
column to obtain 668 mg (60%) of product 22,13 195 mg
(15%) of product 25: white solid; mp 178–180 8C;
1
3356, 2930, 1728, 1451, 1196 cm21; H NMR (CDCl3): d
4.96 (1H, dd, J1¼4.7 Hz, J2¼7.6 Hz, H-15), 4.79 (1H, d,
J¼1.8 Hz, H-27a), 4.73 (1H, d, J¼1.8 Hz, H-27b), 3.63
(3H, s, COOCH3), 3.40 (1H, dd, J1¼0.0 Hz, J2¼9.0 Hz, H-

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A. Garcıa-Granados et al. / Tetrahedron 60 (2004) 1491–1503
1500
[a]2D5¼40 (c 0.9, CHCl3); IR (CHCl3): n 2947, 1729,
1245 cm21; 1H NMR (CDCl3): d 5.66 (1H, dd, J1¼3.3 Hz,
J2¼8.1 Hz, H-15), 4.84 (1H, dd, J1¼J2¼9.3 Hz, H-12), 4.44
(1H, dd, J1¼5.8 Hz, J2¼10.4 Hz, H-3), 3.55 (3H, s,
COOCH3), 2.71 (1H, dd, J1¼6.0 Hz, J2¼13.5 Hz, H-18),
2.02 (3H, s, COCH3), 1.57 (3H, s, Me), 1.07 (3H, s, Me),
0.96 (3H, s, Me), 0.92 (3H, s, Me), 0.90 (3H, s, Me), 0.83
(3H, s, Me), 0.82 (3H, s, Me); 13C NMR (CDCl3): d 15.8
(C-25), 16.5 (C-24), 18.6 (C-6), 20.6 (C-27), 21.4 (COCH3),
23.4 (C-2), 25.7 (C-30), 27.6 (C-26), 27.9 (C-23), 29.2
(C-11), 30.9 (C-20), 31.9, 32.3 and 33.9 (C-7, C-21 and
C-22), 32.3 (C-29), 37.1 (C-1), 37.5 (C-16), 37.7 (C-4), 37.7
(C-10), 39.6 (C-8), 41.0 (C-19), 41.4 (C-18), 43.7 (C-13),
51.2 (C-17), 51.3 (C-9), 51.7 (COOCH3), 55.6 (C-5), 66.0
(C-12), 80.7 (C-3), 121.6 (C-15), 157.4 (C-14), 171.0
(COCH3), 178.3 (C-28); HRLSIMS, m/z: [MþNa]þ
613.2874 (C33H51O4BrNa, calcd 613.2868); 53 mg (5%)
of 27: white solid; mp 168–170 8C; [a]2D5¼15 (c 0.6,
(CDCl3): d 5.53 (1H, d, J1¼5.9 Hz, H-11), 5.51 (1H, d,
J1¼5.9 Hz, H-12), 5.11 (1H, ddd, J1¼4.5 Hz, J2¼10.4 Hz,
J3¼11.7 Hz, H-2), 4.72 (1H, d, J¼10.4 Hz, H-3), 3.60 (3H,
s, COOCH3), 2.97 (1H, dd, J1¼4.3 Hz, J2¼14.2 Hz, H-18),
2.02 (3H, s, COCH3), 1.96 (3H, s, COCH3), 1.25 (3H, s,
Me), 0.95 (3H, s, Me), 0.90 (3H, s, Me), 0.89 (3H, s, Me),
0.88 (3H, s, Me), 0.87 (3H, s, Me), 0.86 (3H, s, Me); 13C
NMR (CDCl3): d 17.7 (Me), 18.2 (C-6), 20.3 (Me), 20.3
(Me), 21.0 (COCH3), 21.2 (COCH3), 23.7 (Me), 23.7
(C-16), 25.9 (Me), 26.9 (C-15), 28.6 (Me), 30.7 (C-20), 32.0
(C-7), 32.2 (C-22), 33.0 (Me), 33.8 (C-21), 39.2 (C-4), 39.7
(C-18), 39.8 (C-8), 40.7 (C-10), 42.3 (C-14), 42.5 (C-1),
45.8 (C-19), 46.1 (C-17), 51.0 (C-5), 51.7 (COOCH3), 70.4
(C-2), 80.4 (C-3), 116.3 (C-11), 120.5 (C-12), 145.8 (C-13),
152.8 (C-9), 170.6 (COCH3), 170.9 (COCH3), 178.3 (C-28);
HRLSIMS, m/z: [MþNa]þ 591.3664 (C35H52O6Na, calcd
591.3661).
1
CHCl3); IR (CHCl3): n 2928, 1728, 1244 cm21; H NMR
4.2.15. Photolysis of 20. Product 20 (325 mg, 0.7 mmol)
was dissolved in 65 mL of ethanol and irradiated in a
borosilicate flask using a 125 W high-pressure Hg street
lamp with the outermost glass shell removed. After 20 min,
the solvent was evaporated and the residue chromato-
graphed on a silica gel column to obtain 308 mg (95%) of
30: white solid; mp 196–198 8C; [a]2D5¼145 (c 0.7, CHCl3);
IR (CHCl3): n 3442, 2945, 1727 cm21; 1H NMR (CDCl3): d
5.98 (1H, d, J¼12.8 Hz, H-12), 5.80 (1H, d, J¼12.8 Hz,
H-11), 3.60 (3H, s, COOCH3), 3.24 (1H, dd, J1¼4.9 Hz,
J2¼11.3 Hz, H-3), 2.77 (1H, dd, J1¼3.6 Hz, J2¼12.7 Hz,
H-18), 1.47 (3H, s, 3H-27), 1.25 (3H, s, 3H-26), 1.08 (3H, s,
3H-25), 1.00 (3H, s, 3H-23), 0.86 (3H, s, 3H-30), 0.85 (3H,
s, 3H-29), 0.81 (3H, s, 3H-24); 13C NMR (CDCl3): d 15.6
(C-24), 18.8 (C-6), 20.8 (C-27), 21.5 (C-26), 21.9 (C-25),
22.7 (C-16), 25.0 (C-30), 28.0 (C-2), 28.3 (C-23), 29.8
(C-7), 30.7 (C-20), 32.8 (C-22), 33.0 (C-29), 34.1 (C-21),
34.3 (C-15), 36.0 (C-1), 37.1 (C-18), 38.6 and 39.0 (C-4
and C-10), 43.0 (C-19), 45.4 (C-17), 50.7 (C-5), 51.7
(COOCH3), 79.0 (C-3), 127.3 (C-11), 127.8 (C-14), 129.8
(C-8), 132.9 (C-12), 134.5 (C-13), 138.0 (C-9), 178.4
(C-28); HRLSIMS, m/z: [MþNa]þ 491.3511 (C31H48O3Na,
calcd 491.3501).
(CDCl3): d 4.97 (1H, dd, J1¼4.9 Hz, J2¼7.7 Hz, H-15),
4.78 (1H, d, J¼1.7 Hz, H-27a), 4.74 (1H, d, J¼1.7 Hz,
H-27b), 4.44 (1H, dd, J1¼6.0 Hz, J2¼9.5 Hz, H-3), 3.64
(3H, s, COOCH3), 3.40 (1H, dd, J1¼0.0 Hz, J2¼9.4 Hz,
H-12), 3.30 (1H, dd, J1¼2.4 Hz, J2¼12.5 Hz, H-18), 2.18
(1H, dd, J1¼2.1 Hz, J2¼4.9 Hz, H-16), 0.96 (3H, s, Me),
0.93 (3H, s, Me), 0.86 (3H, s, Me), 0.86 (3H, s, Me), 0.86
(3H, s, Me), 0.83 (3H, s, Me); 13C NMR (CDCl3): d 15.5
(C-25), 16.4 (C-24), 19.0 (C-6), 21.4 (COCH3), 22.3 (C-30),
23.5 (C-2), 27.1 (C-7), 27.5 and 28.2 (C-23 and C-29), 29.7
(C-20), 31.9 (C-26), 31.9 (C-16), 33.7 and 34.7 (C-21 and
C-22), 36.8 (C-10), 37.8 (C-4), 37.9, 38.0 and 38.6 (C-1,
C-11 and C-19), 41.1 (C-18), 42.0 (C-12), 46.2 (C-8), 50.4
(C-17), 51.9 (COOCH3), 56.4 (C-5), 59.6 (C-9), 81.2 (C-3),
105.4 (C-27), 113.1 (C-15), 155.5 (C-13), 157.1 (C-14),
171.0 (COCH3), 179.9 (C-28); HRLSIMS, m/z: [MþNa]þ
533.3612 (C33H50O4Na, calcd 533.3607); and 191 mg
(15%) of 29: white solid; mp 185–187 8C; [a]2D5¼96 (c 1,
CHCl3); IR (CHCl3): n 2951, 1729, 1461, 1369, 1246,
1
1031 cm21; H NMR (CDCl3): d 5.89 (1H, s, H-19), 5.76
(1H, s, H-11), 4.44 (1H, dd, J1¼5.2 Hz, J2¼11.0 Hz, H-3),
3.58 (3H, s, COOCH3), 1.99 (3H, s, COCH3), 1.21 (3H, s,
3H-25), 1.04 (3H, s, 3H-29), 1.01 (3H, s, 3H-26), 0.92 (3H,
s, 3H-30), 0.83 (3H, s, 3H-23), 0.82 (3H, s, 3H-27), 0.82
(3H, s, 3H-24); 13C NMR (CDCl3): d 16.5 (C-27), 16.7 (C-
24), 17.9 (C-6), 21.2 (COCH3), 21.8 (C-26), 24.0 (C-2), 25.4
(C-25), 26.8 (C-15), 28.0 (C-23), 28.1 (C-30), 29.3 (C-29),
32.3 (C-22), 33.1 (C-7), 33.1 (C-20), 33.4 (C-21), 34.1 (C-
16), 36.7 (C-1), 37.8 (C-4), 38.7 (C-10), 42.1 (C-8), 45.8 (C-
14), 47.4 (C-17), 51.2 (C-5), 51.9 (COOCH3), 80.0 (C-3),
113.0 (C-12), 123.0 (C-11), 131.4 (C-18), 139.3 (C-13),
141.2 (C-19), 155.9 (C-9), 170.8 (COCH3), 176.8 (C-28);
HRLSIMS, m/z: [MþNa]þ 609.2548 (C33H47O4BrNa, calcd
609.2555).
4.2.16. Photolysis of 21. A solution of 325 mg (0.7 mmol)
of product 21 in 65 mL of ethanol was irradiated for 20 min
in a borosilicate flask using a 125 W high-pressure Hg street
lamp with the outermost glass shell removed. The reaction
mixture was evaporated. Chromatography over silica gel
yielded 310 mg (95%) of 31: syrup; [a]2D5¼48 (c 1, CHCl3);
IR (CHCl3): n 3423, 2946, 1729, 1459, 1255, 1170,
1
1046 cm21; H NMR (CDCl3): d 6.03 (1H, d, J¼12.8 Hz,
H-12), 5.80 (1H, d, J¼12.8 Hz, H-11), 3.72 (1H, ddd, J1¼
4.6 Hz, J2¼10.6 Hz, J3¼10.6 Hz, H-2), 3.61 (3H, s,
COOCH3), 3.05 (1H, d, J¼10.6 Hz, H-3), 2.79 (1H, dd,
J1¼4.0 Hz, J2¼12.5 Hz, H-18), 1.50 (3H, s, Me), 1.41 (3H,
s, Me), 1.29 (3H, s, Me), 1.14 (3H, s, Me), 1.05 (3H, s, Me),
0.86 (3H, s, Me), 0.86 (3H, s, Me); 13C NMR (CDCl3): d
16.7 (Me), 18.8 (C-6), 20.9 (Me), 21.5 (Me), 22.7 (C-16),
23.2 (Me), 25.0 (Me), 28.8 (Me), 29.7 and 29.9 (C-7 and
C-22), 30.8 (C-20), 32.9 (C-15), 33.0 (Me), 34.1 (C-21),
37.1 (C-18), 39.1 and 39.7 (C-4 and C-10), 43.0 (C-1), 43.9
(C-19), 45.5 (C-17), 50.5 (C-5), 51.7 (COOCH3), 69.7
(C-2), 83.8 (C-3), 126.8 (C-11), 128.3 (C-14), 129.5 (C-13),
133.1 (C-12), 134.4 (C-8), 137.6 (C-9), 178.5 (C-28);
4.2.14. Treatment of 6 with NBS. Product 6 (1.2 g,
2.1 mmol) was dissolved in 30 mL of CCl4, and 374 mg
(2.1 mmol) of NBS and a catalytic amount of AIBN were
added. The reaction mixture was maintained at reflux for 1 h,
and then extracted with a solution of NaHCO3, dried over
anhydrous Na2SO4, evaporated to dryness and chromato-
graphed on a silica gel column to obtain 1.1 g (90%) of 23:
white solid; mp 191–193 8C; [a]2D5¼152 (c 1, CHCl3);
1
IR (CHCl3): n 2948, 1741, 1369, 1250 cm21; H NMR

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A. Garcıa-Granados et al. / Tetrahedron 60 (2004) 1491–1503
1501
HRLSIMS, m/z: [MþNa]þ 507.3444 (C31H48O4Na, calcd
(3H, s, COOCH3), 3.24 (1H, dd, J1¼4.7 Hz, J2¼11.3 Hz,
H-3), 3.13 (1H, dd, J1¼3.1 Hz, J2¼12.7 Hz, H-18), 1.66
(3H, s, 3H-26), 1.64 (3H, s, 3H-27), 1.01 (3H, s, Me), 1.01
(3H, s, Me), 1.00 (3H, s, Me), 0.88 (3H, s, Me), 0.81 (3H, s,
Me); 13C NMR (CDCl3): d 15.5 (C-24), 18.7 (C-6), 19.1
(C-27), 20.4 (C-25), 21.4 (C-26), 22.5 (C-16), 24.1 (C-30),
28.0 (C-2), 28.1 (C-23), 30.7 (C-7), 30.9 (C-20), 32.1
(C-22), 32.9 (C-18), 33.3 (C-29), 33.8 and 34.2 (C-15 and
C-21), 36.6 (C-1), 38.1 (C-10), 39.0 (C-4), 42.2 (C-19), 45.7
(C-17), 50.6 (C-5), 51.7 (COOCH3), 79.0 (C-3), 123.2
(C-11), 126.8 (C-8), 129.5 (C-14), 131.3 (C-12), 132.5
(C-13), 141.6 (C-9), 178.2 (C-28); HRLSIMS, m/z:
[MþNa]þ 491.3509 (C31H48O3Na, calcd 491.3501).
507.3450).
4.2.17. Photolysis of 22. A solution of 350 mg (0.7 mmol)
of product 22 in 65 mL of ethanol was irradiated for 20 min
in a borosilicate flask using a 125 W high-pressure Hg street
lamp with the outermost glass shell removed. The reaction
mixture was evaporated. Chromatography over silica gel
yielded 332 mg (95%) of 32: syrup; [a]2D5¼157 (c 1,
1
CHCl3); IR (CHCl3): n 2946, 1731, 1247 cm21; H NMR
(CDCl3): d 5.90 (1H, d, J¼12.8 Hz, H-12), 5.80 (1H, d,
J¼12.8 Hz, H-11), 4.52 (1H, dd, J1¼5.0 Hz, J2¼11.3 Hz,
H-3), 3.62 (3H, s, COOCH3), 2.79 (1H, dd, J1¼3.9 Hz,
J2¼12.7 Hz, H-18), 2.04 (3H, s, COCH3), 1.48 (3H, s,
3H-27), 1.27 (3H, s, 3H-26), 1.10 (3H, s, 3H-25), 0.89, 0.88
and 0.88 (3H each, s, 3H-23, 3H-24 and 3H-30), 0.85 (3H, s,
3H-29); 13C NMR (CDCl3): d 16.7 (C-24), 18.8 (C-6), 20.8
(C-27), 21.4 and 21.5 (C-26 and COCH3), 22.0 (C-25), 22.7
(C-16), 24.4 (C-2), 25.0 (C-30), 28.3 (C-23), 29.8 (C-7),
30.8 (C-20), 32.9 (C-22), 33.0 (C-29), 34.1 (C-15), 34.1
(C-21), 35.5 (C-1), 37.1 (C-18), 37.9 and 38.6 (C-4 and
C-10), 43.1 (C-19), 45.4 (C-17), 50.6 (C-5), 51.7
(COOCH3), 81.0 (C-3), 127.3 (C-11), 128.0 (C-14), 129.7
(C-8), 132.9 (C-12), 134.5 (C-13), 137.8 (C-9), 171.1
(COCH3), 178.4 (C-28); HRLSIMS, m/z: [MþNa]þ
533.3600 (C33H50O4Na, calcd 533.3607).
4.2.20. Isomerization of 31 with I2. 5 mg (0.02 mmol) of
iodine were added to a solution of 50 mg (0.1 mmol) of
product 31 in 50 mL of hexane. After 5 h at light reflux,
0.5 mL of sodium bisulfite were added. The reaction
mixture was washed with water, dried over anhydrous
Na2SO4 and evaporated to dryness. Chromatography over
silica gel yielded 10 mg (20%) of starting material and
31 mg (60%) of product 35: syrup; [a]2D5¼69 (c 1, CHCl3);
IR (CHCl3): n 3422, 2946, 1727, 1456, 1257, 1171 cm21
;
1H NMR (CDCl3): d 6.17 (1H, d, J¼16.2 Hz, H-12), 5.96
(1H, d, J¼16.2 Hz, H-11), 3.71 (1H, ddd, J1¼4.2 Hz, J2¼
9.5 Hz, J3¼11.5 Hz, H-2), 3.62 (3H, s, COOCH3), 3.13 (1H,
dd, J1¼3.0 Hz, J2¼12.7 Hz, H-18), 3.03 (1H, d, J¼9.5 Hz,
H-3), 1.66 and 1.64 (3H each, s, 3H-26 and 3H-27), 1.08
(3H, s, Me), 1.05 (3H, s, Me), 1.02 (3H, s, Me), 0.89 (3H, s,
Me), 0.85 (3H, s, Me); 13C NMR (CDCl3): d 16.6 (Me), 18.7
(C-6), 19.1 (Me), 21.4 (Me), 21.6 (Me), 22.5 (C-16), 24.2
(Me), 28.6 (Me), 30.7 (C-7), 30.9 (C-20), 32.1 (C-22),
33.0 (Me), 33.4 (C-18), 33.6 and 34.2 (C-15 and C-21),
39.1 and 39.2 (C-4 and C-10), 42.3 and 44.6 (C-1 and C-19),
45.7 (C-17), 50.6 (C-5), 51.7 (COOCH3), 69.6 (C-2),
83.8 (C-3), 122.7 (C-11), 127.0 (C-8), 129.8 (C-14),
131.8 (C-12), 132.4 (C-13), 141.1 (C-9), 178.2 (C-28);
HRLSIMS, m/z: [MþNa]þ 507.3450 (C31H48O4Na, calcd
507.3450).
4.2.18. Photolysis of 23. Product 23 (400 mg, 0.7 mmol)
was dissolved in 65 mL of ethanol and irradiated in a
borosilicate flask using a 125 W high-pressure Hg street
lamp with the outermost glass shell removed. After 20 min,
the solvent was evaporated and the residue chromato-
graphed on a silica gel column to obtain 381 mg (95%) of
33: white solid; mp 169–171 8C; [a]2D5¼29 (c 0.7, CHCl3);
IR (CHCl3): n 2948, 1740, 1250 cm21; 1H NMR (CDCl3): d
6.02 (1H, d, J¼12.6 Hz, H-12), 5.78 (1H, d, J¼12.6 Hz,
H-11), 5.09 (1H, ddd, J1¼4.5 Hz, J2¼10.5 Hz, J3¼15.0 Hz,
H-2), 4.82 (1H, d, J¼10.5 Hz, H-3), 3.66 (3H, s, COOCH3),
2.81 (1H, dd, J1¼3.4 Hz, J2¼12.3 Hz, H-18), 2.03 (3H, s,
COCH3), 1.96 (3H, s, COCH3), 1.44 (3H, s, Me), 1.23 (3H,
s, Me), 1.16 (3H, s, Me), 0.92 (3H, s, Me), 0.91 (3H, s, Me),
0.87 (3H, s, Me), 0.85 (3H, s, Me); 13C NMR (CDCl3): d
17.6 (C-24), 18.6 (C-6), 20.7 (C-27), 21.0 (C-26), 21.2
(COCH3), 21.7 (COCH3), 22.7 (C-16), 22.7 (C-25), 24.9
(C-30), 28.5 (C-23), 29.8 (C-7), 30.7 (C-20), 32.9 (C-22),
33.0 (C-29), 34.2 (C-15), 34.2 (C-21), 37.0 (C-18), 39.3
(C-4), 39.6 (C-10), 40.7 (C-1), 43.0 (C-19), 45.4 (C-17),
51.8 (C-5), 51.8 (COOCH3), 70.9 (C-2), 80.7 (C-3), 127.2
(C-11), 128.1 (C-14), 133.3 (C-12), 133.5 (C-8), 134.4
(C-13), 136.9 (C-9), 170.6 (COCH3), 170.9 (COCH3), 178.3
(C-28); HRLSIMS, m/z: [MþNa]þ 591.3668 (C35H52O6Na,
calcd 591.3662).
4.2.21. Isomerization of 32 with I2. Product 32 (50 mg,
0.1 mmol) was dissolved in 50 mL of hexane and 5 mg
(0.02 mmol) of I2 were added. After 5 h at light reflux,
0.5 mL of sodium bisulfite were added. The reaction
mixture was washed with water, dried over anhydrous
Na2SO4, evaporated to dryness and chromatographed on a
silica gel column to obtain 10 mg (20%) of 32 and 30 mg
(60%) of 36: syrup; [a]2D5¼80 (c 1, CHCl3); IR (CHCl3): n
1
2948, 1729, 1247, 756 cm21; H NMR (CDCl3): d 6.15
(1H, d, J¼16.3 Hz, H-12), 5.94 (1H, d, J¼16.3 Hz, H-11),
4.48 (1H, dd, J1¼4.5 Hz, J2¼11.4 Hz, H-3), 3.59 (3H, s,
COOCH3), 3.11 (1H, dd, J1¼3.3 Hz, J2¼13.1 Hz, H-18),
2.03 (3H, s, COCH3), 1.65 (3H, s, 3H-26), 1.62 (3H, s,
3H-27), 1.02 (3H, s, 3H-25), 0.98 (3H, s, 3H-30), 0.87, 0.87
and 0.86 (3H each, s, 3H-23, 3H-24 and 3H-29); 13C NMR
(CDCl3): d 16.6 (C-24), 18.6 (C-6), 19.0 (C-27), 20.5
(C-25), 21.4 (C-26), 21.4 (COCH3), 22.4 (C-16), 24.1
(C-30), 24.2 (C-2), 28.1 (C-23), 30.6 (C-7), 30.9 (C-20),
32.1 (C-22), 32.9 (C-18), 33.3 (C-29), 33.6 and 34.1 (C-15
and C-21), 36.2 (C-1), 37.9 (C-4), 37.9 (C-10), 42.2 (C-19),
45.7 (C-17), 50.7 (C-5), 51.7 (COOCH3), 81.0 (C-3), 123.0
(C-11), 126.8 (C-8), 129.5 (C-14), 131.4 (C-12), 132.4
(C-13), 141.3 (C-9), 171.0 (COCH3), 178.2 (C-28);
4.2.19. Isomerization of 30 with I2. Product 30 (45 mg,
0.1 mmol) was dissolved in 50 mL of hexane and 5 mg
(0.02 mmol) of I2 were added. After 5 h at light reflux,
0.5 mL of sodium bisulfite were added. The reaction
mixture was washed with water, dried over anhydrous
Na2SO4, evaporated to dryness and chromatographed on a
silica gel column to obtain 9 mg (20%) of 30 and 27 mg
(60%) of 34: syrup; [a]2D5¼52 (c 0.6, CHCl3); IR (CHCl3):
n 3349, 1639 cm21 1H NMR (CDCl3): d 6.16 (1H, d,
;
J¼16.3 Hz, H-12), 5.97 (1H, d, J¼16.3 Hz, H-11), 3.61

´
A. Garcıa-Granados et al. / Tetrahedron 60 (2004) 1491–1503
1502
HRLSIMS, m/z: [MþNa]þ 533.3602 (C33H50O4Na, calcd
J3¼11.6 Hz, H-2), 3.62 (3H, s, COOCH3), 3.03 (1H, d, J¼
9.5 Hz, H-3), 2.90 (1H, dd, J1¼9.6 Hz, J2¼15.4 Hz, H-12a),
2.75 (1H, dd, J1¼4.3 Hz, J2¼15.4 Hz, H-12b), 1.51 (3H, s,
Me), 1.02 (3H, s, Me), 1.00 (3H, s, Me), 0.89 (3H, s, Me),
0.87 (3H, s, Me), 0.84 (3H, s, Me); 13C NMR (CDCl3): d
16.7 (Me), 19.0 (Me), 20.8 (Me), 22.9 and 23.1 (C-6 and
C-16), 24.4 (Me), 28.9 (Me), 30.0 (C-15), 30.7 and 32.2
(C-12 and C-22), 30.7 (C-20), 33.0 (Me), 34.1 (C-21), 36.2
(C-18), 37.1 (C-7), 39.7 and 41.6 (C-4 and C-10), 41.5
(C-1), 43.3 (C-19), 45.8 (C-17), 51.8 and 52.7 (C-5 and
COOCH3), 69.5 (C-2), 83.9 (C-3), 112.7 (C-26), 117.8
(C-11), 125.2 (C-14), 133.4 (C-13), 144.9 (C-9), 150.1
(C-8), 178.4 (C-28); HRLSIMS, m/z: [MþNa]þ 507.3444
(C31H48O4Na, calcd 507.3450).
533.3607).
4.2.22. Isomerization of 33 with I2. 5 mg (0.02 mmol) of
iodine were added to a solution of 55 mg (0.1 mmol) of
product 33 in 50 mL of hexane. After 5 h at light reflux,
0.5 mL of sodium bisulfite were added. The reaction
mixture was washed with water, dried over anhydrous
Na2SO4 and evaporated to dryness. Chromatography over
silica gel yielded 11 mg (20%) of starting material and
34 mg (60%) of 37: syrup; [a]2D5¼1 (c 1, CHCl3); IR
(CHCl3): n 2949, 1739, 1369, 1249 cm21 1H NMR
;
(CDCl3): d 6.19 (1H, d, J¼16.0 Hz, H-12), 5.91 (1H, d,
J¼16.0 Hz, H-11), 5.14 (1H, ddd, J1¼4.0 Hz, J2¼11.3 Hz,
J3¼11.3 Hz, H-2), 4.75 (1H, d, J¼11.3 Hz, H-3), 3.60 (3H,
s, COOCH3), 3.10 (1H, dd, J1¼2.8 Hz, J2¼13.0 Hz, H-18),
2.04 (3H, s, COCH3), 1.96 (3H, s, COCH3), 1.69 (3H, s,
Me), 1.63 (3H, s, Me), 1.17 (3H, s, Me), 0.98 (3H, s, Me),
0.93 (3H, s, Me), 0.91 (3H, s, Me), 0.86 (3H, s, Me); 13C
NMR (CDCl3): d 17.5 (Me), 18.6 (C-6), 19.1 (Me), 21.0
(COCH3), 21.2 (COCH3), 21.5 (Me), 21.5 (Me), 22.4
(C-16), 24.0 (Me), 28.4 (Me), 29.8 (C-7), 30.6 and 33.4
(C-21 and C-22), 30.9 (C-20), 33.0 (Me), 33.3 (C-18), 34.1
(C-15), 38.9 and 39.4 (C-4 and C-10), 42.2 (C-19), 42.3
(C-1), 45.7 (C-17), 50.1 (C-5), 51.7 (COOCH3), 70.4 (C-2),
80.6 (C-3), 122.4 (C-11), 127.1 (C-8), 130.0 (C-14), 131.7
(C-12), 132.3 (C-13), 140.3 (C-9), 170.3 (COCH3), 170.9
(COCH3), 178.1 (C-28); HRLSIMS, m/z: [MþNa]þ
591.3664 (C35H52O6Na, calcd 591.3662).
4.2.25. Acetylation of 38. Product 38 (100 mg, 0.2 mmol)
was dissolved in 4 mL of pyridine and 2 mL of Ac2O and
stirred for 1 h at reflux. The reaction mixture was diluted
with water, extracted with CH2Cl2, washed with saturated
aqueous KHSO4 solution and dried with anhydrous Na2SO4.
The solvent was evaporated at reduced pressure and the
residue was chromatographed on a silica gel column to give
104 mg (95%) of 40: syrup; [a]2D5¼38 (c 0.6, CHCl3); IR
1
(CHCl3): n 2946, 1730, 1242 cm21; H NMR (CDCl3): d
5.00 (1H, d, J¼2.4 Hz, H-26a), 4.96 (1H, dd, J1¼4.5 Hz,
J2¼9.5 Hz, H-11), 4.55 (1H, d, J¼2.4 Hz, H-26b), 4.50 (1H,
dd, H-3), 3.63 (3H, s, COOCH3), 2.05 (3H, s, COCH3), 1.51
(3H, s, 3H-27), 0.97 (3H, s, 3H-25), 0.90 (3H, s, 3H-23),
0.89 (3H, s, 3H-30), 0.88 (3H, s, 3H-29), 0.86 (3H, s,
3H-24); 13C NMR (CDCl3): d 16.7 (C-24), 19.0 (C-27), 20.9
(C-25), 21.4 (COCH3), 23.1 (C-6), 23.1 (C-16), 24.4 (C-30),
24.4 (C-2), 28.3 (C-23), 30.0 and 30.8 (C-12 and C-15), 30.7
(C-20), 32.2 (C-22), 33.0 (C-29), 34.1 (C-21), 34.9 (C-1),
36.4 (C-18), 37.1 (C-7), 38.4 (C-4), 40.4 (C-10), 41.6
(C-19), 45.8 (C-17), 51.8 (COOCH3), 52.8 (C-5), 81.1
(C-3), 112.2 (C-26), 117.6 (C-11), 125.2 (C-14), 133.5
(C-13), 145.3 (C-8), 150.6 (C-9), 171.0 (COCH3), 178.2
(C-28); HRLSIMS, m/z: [MþNa]þ 533.3601 (C33H50O4Na,
calcd 533.3607).
4.2.23. Photolysis of 30. Product 30 (325 mg, 0.7 mmol)
was dissolved in 65 mL of ethanol and irradiated in a quartz
flask using a 125 W high-pressure Hg street lamp with the
outermost glass shell removed. After 30 min, the solvent
was evaporated and the residue chromatographed on a silica
gel column to obtain 309 mg (95%) of 38: syrup; [a]2D5¼20
1
(c 1, CHCl3); IR (CHCl3): n 3445, 2945, 1726 cm21; H
NMR (CDCl3): d 4.99 (1H, d, J¼2.3 Hz, H-26a), 4.93 (1H,
dd, J1¼4.5 Hz, J2¼9.4 Hz, H-11), 4.53 (1H, d, J¼2.3 Hz,
H-26b), 3.60 (3H, s, COOCH3), 3.23 (1H, dd, J1¼4.9 Hz,
J2¼10.0 Hz, H-3), 1.51 (3H, s, 3H-27), 0.97 (3H, s, 3H-25),
0.94 (3H, s, 3H-23), 0.89 (3H, s, 3H-30), 0.87 (3H, s,
3H-29), 0.81 (3H, s, 3H-24); 13C NMR (CDCl3): d 15.5
(C-24), 19.0 (C-27), 20.8 (C-25), 23.0 and 23.2 (C-6 and
C-16), 24.3 (C-30), 27.9 (C-2), 28.4 (C-23), 29.9 and 30.5
(C-12 and C-15), 30.7 (C-20), 32.2 (C-22), 33.0 (C-29), 34.1
(C-21), 35.2 (C-1), 36.0 (C-18), 37.3 (C-7), 39.5 (C-4), 40.6
(C-10), 41.5 (C-19), 45.8 (C-17), 51.7 (COOCH3), 52.7
(C-5), 79.1 (C-3), 112.1 (C-26), 117.2 (C-11), 125.0 (C-14),
133.5 (C-13), 145.4 (C-8), 151.0 (C-9), 178.3 (C-28);
HRLSIMS, m/z: [MþNa]þ 491.3502 (C31H48O3Na, calcd
491.3501).
4.2.26. Photolysis of 33. Product 33 (390 mg, 0.7 mmol)
was dissolved in 65 mL of ethanol and irradiated in a quartz
flask using a 125 W high-pressure Hg street lamp with the
outermost glass shell removed. After 30 min, the solvent
was evaporated and the residue chromatographed on a silica
gel column to obtain 370 mg (95%) of 41: white solid; mp
71–73 8C; [a]2D5¼28 (c 1, CHCl3); IR (CHCl3): n 2946,
2356, 1743, 1251 cm21; 1H NMR (CDCl3): d 5.19 (1H, ddd,
J1¼3.9 Hz, J2¼11.2 Hz, J3¼11.2 Hz, H-2), 5.04 (1H, d,
J¼2.1 Hz, H-26a), 4.88 (1H, dd, J1¼4.3 Hz, J2¼9.5 Hz,
H-11), 4.76 (1H, d, J¼11.2 Hz, H-3), 4.58 (1H, d, J¼
2.1 Hz, H-26), 3.64 (3H, s, COOCH3), 2.89 (1H, dd,
J1¼9.5 Hz, J2¼15.5 Hz, H-12a), 2.73 (1H, dd, J1¼4.3 Hz,
J2¼15.5 Hz, H-12b), 2.05 (3H, s, COCH3), 2.00 (3H, s,
COCH3), 1.51 (3H, s, Me), 1.08 (3H, s, Me), 0.93 (3H, s,
Me), 0.90 (3H, s, Me), 0.89 (3H, s, Me), 0.88 (3H, s, Me);
13C NMR (CDCl3): d 17.6 (Me), 19.0 (Me), 21.0 (Me), 21.2
(COCH3), 21.6 (COCH3), 22.9 (C-6), 23.0 (C-16), 24.3
(Me), 28.6 (Me), 29.8 (C-15), 29.9 (C-20), 30.6 (C-12), 30.7
(C-22), 33.0 (Me), 34.1 (C-21), 36.2 (C-18), 36.8 (C-7),
39.7 (C-4), 40.8 (C-1), 41.4 (C-10), 41.6 (C-19), 45.8
(C-17), 51.8 (COOCH3), 52.3 (C-5), 70.6 (C-2), 80.6 (C-3),
113.0 (C-26), 117.9 (C-11), 125.3 (C-14), 133.2 (C-13),
4.2.24. Photolysis of 31. A solution of 325 mg (0.7 mmol)
of product 31 in 65 mL of ethanol was irradiated for 30 min
in a quartz flask using a 125 W high-pressure Hg street lamp
with the outermost glass shell removed. The reaction
mixture was evaporated. Chromatography over silica gel
yielded 311 mg (95%) of 39: syrup; [a]2D5¼32 (c 1, CHCl3);
IR (CHCl3): n 3412, 2945, 1727, 1462, 1255, 1170 cm21
;
1H NMR (CDCl3): d 5.02 (1H, d, J¼2.3 Hz, H-26a), 4.95
(1H, dd, J1¼4.3 Hz, J2¼9.6 Hz, H-11), 4.56 (1H, d, J¼
2.3 Hz, H-26b), 3.78 (1H, ddd, J1¼4.0 Hz, J2¼9.5 Hz,

´
A. Garcıa-Granados et al. / Tetrahedron 60 (2004) 1491–1503
1503
Int. Appl. W0 043331, 1998; (Chem. Abstr. 1998, 128,
179706).
144.4 (C-9), 149.5 (C-8), 170.5 (COCH3), 170.8 (COCH3),
178.2 (C-28); HRLSIMS, m/z: [MþNa]þ 591.3670
(C35H52O6Na, calcd 591.3662).
3. Manna, S.; Yadagiri, P.; Falck, J. Chem. Soc., Chem. Commun.
1987, 1324–1325.
4. Liu, J. Ethnopharmacol. 1995, 49, 57–68.
4.2.27. Photolysis of 41. A solution of 340 mg (0.6 mmol)
of product 41 in 55 mL of ethanol was irradiated for 30 min
in a quartz flask using a 125 W high-pressure Hg street lamp
with the outermost glass shell removed. The reaction
mixture was evaporated. Chromatography over silica gel
yielded 175 mg (50%) of starting material and 154 mg
(45%) of 42: white solid; mp 100–102 8C; [a]2D5¼25 (c 1,
5. Garcia-Granados, A.; Duen˜as, J.; Moliz, J. N.; Parra, A.;
Perez, F. L.; Dobado, J. A.; Molina, J. J. Chem. Res. (S) 2000,
56–57. Garcia-Granados, A.; Duen˜as, J.; Moliz, J. N.; Parra,
A.; Perez, F. L.; Dobado, J. A.; Molina, J. J. Chem. Res. (M)
2000, 2, 0326–0339. Garcia-Granados, A.; Duen˜as, J.;
Melguizo, E.; Moliz, J. N.; Parra, A.; Perez, F. L.; Dobado,
J. A.; Molina, J. J. Chem. Res. (S) 2000, 212–213. Garcia-
Granados, A.; Duen˜as, J.; Melguizo, E.; Moliz, J. N.; Parra, A.;
Perez, F. L.; Dobado, J. A.; Molina, J. J. Chem. Res. (M) 2000,
2, 0653–0670.
1
CHCl3); IR (CHCl3): n 2947, 1733, 1249 cm21; H NMR
(CDCl3): d 5.15 (1H, ddd, J1¼4.6 Hz, J2¼10.7 Hz, J3¼
11.3 Hz, H-2), 4.78 (1H, d, J¼10.7 Hz, H-3), 3.59 (3H, s,
COOCH3), 3.05 (1H, m, H-11), 2.65 (1H, dd, J1¼3.7 Hz,
J2¼10.3 Hz, H-18), 2.27 (1H, dd, J1¼4.2 Hz, J2¼13.0 Hz,
H-26), 2.05 (3H, s, COCH3), 2.00 (3H, s, COCH3), 1.52
(3H, s, Me), 1.12 (3H, s, Me), 0.97 (3H, s, Me), 0.90 (3H, s,
Me), 0.90 (3H, s, Me), 0.90 (3H, s, Me); 13C NMR (CDCl3):
d 17.3 (C-24), 19.3 (C-6), 19.6 (C-27), 21.0 (C-25), 21.0
(COCH3), 21.3 (COCH3), 22.6 (C-16), 24.3 (C-30), 26.6
(C-15), 28.3 (C-23), 29.9 (C-21), 30.8 (C-20), 32.2 (C-22),
32.9 (C-29), 34.0 (C-12), 34.5 (C-7), 35.2 (C-18), 35.3
(C-26), 37.7 (C-4), 38.9 (C-11), 39.5 (C-10), 40.0 (C-1),
41.9 (C-19), 45.8 (C-17), 51.1 (C-5), 51.6 (COOCH3), 70.1
(C-2), 80.9 (C-3), 125.4 (C-14), 132.8 (C-13), 136.8 (C-8),
152.8 (C-9), 170.7 (COCH3), 170.8 (COCH3), 178.4 (C-28);
HRLSIMS, m/z: [MþNa]þ 591.3669 (C35H52O6Na, calcd
591.3662).
6. Rasmusson, G. H.; Reynolds, G. F.; Steinberg, N. G.; Walton,
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´
This work was supported by a grant from the Comision
Interministerial de Ciencia y Tecnologıa and by a project
´
´
from the Ministerio de Educacion y Cultura (No. PM98-
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0213). We thank David Nesbitt for reviewing the language
of the original English manuscript.
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Chapter 36.
References and notes
1. Dictionary of Natural Products on CD-ROM, Chapman and
Hall, ISSN 0966-2146 ver. 5.1 (1996), oleanolic acid CAS
(508-02-01), maslinic acid CAS (4373-41-5).
2. Garcia-Granados, A.; Martinez, A.; Parra, A.; Rivas, F. P.C.T.