Bioactive compounds with added value prepared from terpenes contained in solid wastes from the olive oil industry

Article abstract of DOI:10.1002/cbdv.200900023

Starting from solid wastes from two-phase olive-oil extraction, the pentacyclic triterpenes oleanolic acid and maslinic acid were isolated. These natural compounds were transformed into methyl olean-12-en-28-oate (5), which then was transformed into several seco-C-ring triterpene compounds by chemical and photolytic modifications. The triene seco-products were fragmented through several oxidative procedures to produce, simultaneously, cis- and trans-decalin derivatives, both potential synthons for bioactive compounds. The chemical behavior of the isolated fragments was investigated, and a suitable approach to several low-molecular-weight terpenes was performed. These are interesting processes for the value-addition to solid waste from the olive-oil industry.

Full text of DOI:10.1002/cbdv.200900023

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Bioactive Compounds with Added Value Prepared from Terpenes Contained
in Solid Wastes from the Olive Oil Industry
by Andres Parra*, Pilar E. Lopez, and Andres Garcia-Granados
Departamento de Quimica Organica, Facultad de Ciencias, Universidad de Granada, ES-18071 Granada
(phone: þ34-958-240480; e-mail: aparra@ugr.es)
Starting from solid wastes from two-phase olive-oil extraction, the pentacyclic triterpenes oleanolic
acid and maslinic acid were isolated. These natural compounds were transformed into methyl olean-12-
en-28-oate (5), which then was transformed into several seco-C-ring triterpene compounds by chemical
and photolytic modifications. The triene seco-products were fragmented through several oxidative
procedures to produce, simultaneously, cis- and trans-decalin derivatives, both potential synthons for
bioactive compounds. The chemical behavior of the isolated fragments was investigated, and a suitable
approach to several low-molecular-weight terpenes was performed. These are interesting processes for
the value-addition to solid waste from the olive-oil industry.
Introduction. – The olive-oil industry produces a large volume of wastes, both solid
and liquid, which represents a disposal and potentially enviromental pollution problem.
In fact, olive-oil waste has always been one of the biggest problems associated with this
industry. However, these residues are promising sources in which potentially interesting
compounds remain, such as phenolic compounds (tyrosol, hydroxytyrosol, and
oleuropein), oligosaccharides, mannitol, and two known triterpene acids (oleanolic
acid and maslinic acid), which can be converted into value-added products. Thus, in our
case, the starting vegetal material was the waste product from a two-phase olive-oil
industrial process containing both liquid and solid wastes. This natural starting material
is a renewable source of available triterpenes that can serve to produce chiral
intermediates and other compounds for flavors, fragrances, pharmaceutical products,
and biocontrol agents. The isolated triterpene compounds are oleanolic acid (3b-
hydroxyolean-12-en-28-oic acid; 1) and maslinic acid (2a,3b-dihydroxyolean-12-en-28-
oic acid; 2) (Fig.), two natural pentacyclic triterpenoids widely distributed in nature
[1]. Both acids and several closely related products exhibit a wide range of biological
activities, and some may find application in medicine [2–4]. A method to obtain large
quantities of both triterpene acids from olive-mill wastes has been reported by our
group [5], and these compounds could be useful to semi-synthesize other biologically
or chemically significant products. In fact, oleanenes possess a 4,4,10-trimethyl-
substituted trans-decalin system with the H-atom at C(9) in an a-position (A- and B-
rings), such as drimane sesquiterpenes or related compounds with remarkable
biological, olfactory, and fixative properties [6–8]. Moreover, the bicyclic system
formed by the D- and E-rings is related to naturally occurring tricyclic triterpenes such
as camelliols A and B [9], and other bicyclic and tetracyclic triterpenes (preoleanate-
traene and seco-C-oleanene, resp.) [10]. Therefore, this kind of products could be
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

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useful as starting materials for affording simultaneously remarkable cis- and trans-
decalin-type chiral synthons, vigorously sought by the scientific community [11][12].
On the other hand, the degradation of high-molecular-weight terpene compounds has
frequently been regarded as an efficient way to access suitable molecular fragments for
the synthesis of sesquiterpene compounds [13][14]. For example, Ambroxꢂ has been
synthesized by degradation from natural occurring labdanes such as labdanoic acid,
sclareol, manool, manoyl oxide, and larixol.
Figure. Structures of compounds 1–5
Recently, our research group has reported the solution- and solid-phase synthesis of
several maslinic acid derivatives containing amino acids and peptides, which possess
potent anti-HIV activity [15]. We have also described the remote hydroxylation of the
Me(23) and Me(24) groups of these natural triterpene compounds by a regioselective
cyclopalladation process yielding other natural compounds with potentially interesting
biological activities [16]. In addition, we have reported an initial study of the formation
of several derivatives from oleanolic acid and maslinic acid with a cleaved C-ring [17–
19]. Moreover, deoxygenation of ring A of both acids through different methods has
been described [20][21], and thus, starting from methyl oleanoate (3) or methyl
maslinate (4), methyl olean-12-en-28-oate (5) was obtained.
Here, we report on the process of obtaining different trienes from methyl olean-12-
en-28-oate (5) by an efficient reaction sequence including photochemical and chemical
isomerization reactions. In addition, we present partial syntheses of several drimane-
related fragments obtained from different oxidative cleavages of the C¼C bonds
situated in the opened C ring of the above-mentioned oleantrienes. In summary,
triterpene compound 5, deoxygenated in ring A, was used as a starting material to yield
simultaneously trans- and cis-decalin compounds without OH substituents at the rings.
Moreover, we describe the reactivity of the resulting cis- and trans-decalin fragments, as
well as the decarboxylation of a monocyclic synthon originating from the ring A of the
triterpene skeleton.
Results and Discussion. – 1. Cleavage of the Original Triterpene Molecule at the
C(8)ꢀC(14) Bond. The aim was to fragment the above-mentioned pentacyclic
triterpenes through the C-ring. In a first step, a diene system was formed in this ring
by treatment of product 5 with NBS/AIBN in CCl4. Thus, by a one-step bromination/
dehydrobromination process, compound 6, with a conjugated C¼C bond between C(9)
and C(11), was obtained. Additionally, a minor product, 7, was isolated, with a Me
group migrated from C(14) to C(13) with retention of the orientation of the Me group,

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with a C(14)¼C(15) bond, and with a Br-substituent at C(12) (Scheme 1, path a). In the
second step, the opening of the C-ring of homodiene 6 was achieved by irradiation with
a high-pressure Hg street lamp in a borosilicate flask, yielding triene 8 by a conrotatory
photochemical electrocyclic reaction which permitted the cleavage of the C(8)ꢀC(14)
bond (Scheme 1, path b). With an extra time of 20 min, the exocyclic triene 9 appeared,
which has two conjugated C¼C bonds between C(8) and C(26) and between C(9) and
C(11), and additionally an isolated C¼C bond between C(13) and C(14). These
processes were based on previously known photochemical interconversions of
provitamin D2, lumisterol, previtamin D2, tachysterol, and some derivatives, in
addition to photochemical and thermal transformations of some pentacyclic triterpe-
noids, such as methyl dehydroursolate [22].
Scheme 1. Synthesis of Trienes 8 and 9
a) N-Bromosuccinimide (NBS), 2,2’-azobis(isobutyronitrile) (AIBN), CCl4, reflux, 15 min; 6 (83%) and
7 (10%). b) hn, EtOH, r.t.
2. Oxidative Treatment and Isomerization of cis-Triene 8. In an attempt to cleave the
triterpene molecule at the seco-C-ring, triene 8 was treated with NaIO4/RuCl3 in
acetone/H2O, giving the cyclic ether 10 in a good yield (80%) (Scheme 2, path a);
however, the C(11)¼C(12) bond was not affected. With the same aim, ozonolysis of 8
was performed (Scheme 2, path b). A complex mixture of products was obtained from
several breakups and oxidations of the different C¼C bonds. Several low-molecular-
weight products were obtained, indicating that the C(11)¼C(12) bond had been
cleaved. Compound 11 resulted from the reaction of the C(8)¼C(9) bond with ozone,
forming two CO groups at C(8) and C(9), while the other C¼C bonds remained
unaltered, yielding a triterpene molecule with open B- and C-rings. In compound 12,
ozonolysis cleaved the C(11)¼C(12) bond, but in addition, also the C(8)¼C(9) bond,

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providing a monocyclic fragment, with only the A-ring unaffected. Compounds 13 and
14, fragments containing the D- and E-rings of the former triterpene, were the result of
the fragmentation at the C(11)¼C(12) bond, which yielded the cis-decalin intermedi-
ates, which had been one of the aims of the fragmentation of the triterpene molecule.
Compound 14 contains a g-lactone ring and was formed from 13. After ester hydrolysis,
the oxirane was intramolecularily opened by the acid group.
Scheme 2. Oxidation of cis-Triene 8
a) RuCl3, NaIO4, acetone, H2O, r.t., 30 min, 80%. b) 1. O3, AcOEt, ꢀ788, 7 min; 2. Me2S, r.t., 1 h; 11
(12%), 12 (22%), 13 (25%), and 14 (14%).
Therefore, to minimize undesirable oxidative cleavage, we protected triene 8 by
previous epoxidation with m-chloroperbenzoic acid (MCPBA) under different
reaction conditions (Scheme 3, Table). At low temperature (ꢀ608), only product 15
was formed by epoxidation at the C(8)¼C(9) bond on the a face. At ꢀ408, the yield of
epoxide 15 decreased, and compounds 16–19 were obtained in different yields
depending on the reaction time. Compounds 16 and 17 had, as 15, an epoxy group on
the a face at C(8)ꢀC(9); however, while 16 had a new oxirane group also on the a face
at C(13)ꢀC(14), in product 17, this group had the opposite configuration. Product 18
was epoxidized at C(8)ꢀC(9) on the a face, and a lactone system was formed between
C(28) and C(13). This compound was the result of the attack of the hydrolized
methoxycarbonyl group at C(28) at the C(13) position of the epoxide in compound 16.
This intramolecular reaction led to a compound with an a-OH group at C(14) and a
lactone ring between C(13) and C(28). In turn, compound 19 had an epoxy group at
C(8)ꢀC(9) on the a face and two OH groups at C(13) and C(14). At room
temperature, product 20 was obtained in addition to the other compounds. This
compound had a structure similar to the cyclic ether 10, but in 20, the OH group at C(8)
was eliminated, and a C(7)¼C(8) bond was formed. Ozonolysis of the monoepoxy
derivative 15 furnished products 19 and 20, with the central C¼C bond unaltered. Thus,
although these epoxy and OH triterpene derivatives seemed to be suitable for the

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425
cleavage at the seco-C-ring because they only had one central C¼C bond, attempts to
break up this ring under different conditions were unsuccessful, and the compounds
were recovered unaltered after oxidative treatment.
Scheme 3. Epoxidation of cis-Triene 8
Table. Epoxidation Yields of Triene 8 at Different Temperatures and Times
Temp. [8]
Time [h]
Yield [%]
8
15
16
17
18
19
20
ꢀ60
ꢀ60
ꢀ40
ꢀ40
ꢀ40
r.t.
24
48
3
5
12
2
40
10
–
–
–
55
82
60
42
31
10
–
–
16
10
8
–
–
8
18
20
20
–
–
6
10
15
25
–
–
–
8
4
2
–
–
–
–
–
–
3
10
In addition, since oxidation reactions carried out using several compounds with the
central C¼C bond in (Z)-disposition did not allow the cleavage of the triterpene
skeleton, triene 8 was subjected to several chemical and photolytic isomerizations
(Scheme 4). First, irradiation of triene 8 in a quartz flask for 1 h yielded exocyclic triene
9 (Scheme 4, path a), already produced previously as a by-product in the formation of 8
(Scheme 1, path b). On the other hand, chemical isomerization of cis-triene 8 to trans-
triene 21 was performed by treatment with I2 in hexane (65%) or with TFA in toluene
(95%). However, when cis-triene 8 was treated with TFA in CH2Cl2, a new triene, 22
with two conjugated C¼C bonds between C(7) and C(8) and between C(9) and C(11)
and another one in the original C(13)¼C(14) position, was obtained in high yield
(80%).

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Scheme 4. Isomerization of cis-Triene 8
a) hn, EtOH, r.t., quartz flask, 1 h, 95%. b) I2, hexane, reflux, 5 h, 65%. c) CF3COOH (TFA), toluene,
reflux, 3.5 h, 95%. d) TFA, CH2Cl2, reflux, 5 h; 21 (15%) and 22 (80%).
3. Oxidative Treatment of exo-Triene 9 and trans-Triene 21. The seco-C-ring
triterpene compounds 9 and 21 were independently treated with different oxidazing
reagents. Thus, ozonolysis of triene 9 in AcOEt led to the cleavage of the C(9)¼C(11)
bond, resulting in a mixture of three fragments (Scheme 5, path a; products 23–25).
Compound 23, a ketoepoxy synthon from the A- and B-rings, had a C14 skeleton and is
an adequate precursor for the synthesis of drimane and related compounds. The other
compounds obtained, 24 [18] and 25, presented a C16 skeleton from the D- and E-rings
of the triterpene skeleton.
When the ozonolysis was followed by reduction with NaBH4, a complex mixture of
products was formed (Scheme 5, path b; compounds 26–28). Two of these, compounds
26 and 27, had the A- and B-rings of the starting molecule and differed only in the
configuration of the epoxy group between C(8) and C(11). On the other hand,
compound 28 was similar to compound 24, but the aldehyde at C(13) was reduced to an
alcohol.
Finally, ozonolysis of compound 9 followed by reduction with LiAlH4 (Scheme 5,
path c), gave compounds 29–31, thereof, 31 was the major product and a fragment from
the D- and E-rings with a cyclic ether between C(16) and C(6). Compounds 29 and 30
were also obtained as a result of the C(9)¼C(11) bond rupture and subsequent
reduction of the formed keto and epoxy groups at C(9) and C(8), respectively.
On the other hand, ozonolysis of triene 21 gave better yields of compounds 12 and
13 (Scheme 6), products previously obtained by similar treatment of product 8
(Scheme 2). Treatment of compound 21 with RuCl3/NaIO4 in acetone/H2O at room
temperature for 30 min gave a mixture of two aldehyde sesquiterpenes (32 and 33,
[18]), one of which, drim-8-en-11-al (32), has been used as an appropriate synthon to
produce other remarkable drimane-related compounds [23][24].

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Scheme 5. Ozonolysis of exo-Triene 9
a) 1. O3, AcOEt, ꢀ788, 2 min; 2. Me2S, r.t., 12 h; 23 (24%), 24 (32%), and 25 (16%). b) 1. O3, AcOEt,
ꢀ788, 5 min; 2. NaBH4, i-PrOH, r.t., 2 h; 26 (22%), 27 (9%), and 28 (36%). c) 1. O3, AcOEt, ꢀ788,
5 min; 2. LiAlH4, THF, reflux, 1 h; 29 (20%), 30 (8%), and 31 (25%).
4. Reactivity of Fragments 12, 32, and 33: Partial Syntheses of Ambroxꢂ and cis-
Decalin Synthons. Decarboxylation of compound 12, originating from the A-ring of the
original triterpene, was investigated using two methods, because some feasible products
are interesting synthons related to mono- and tricyclic triterpenes such as elengasidiol
[25], achilleols A and B [26], camelliol A [9], mokupalide [27], and other important
compounds such as (þ)-(4R)-manoalide [28], (ꢀ)-Ambroxꢂ [29], and ambrinol [30].
Thus, treatment of compound 12 with Pb(OAc)4 [31] gave a complex mixture of
alkenes (34–36) [32] and the acetylated derivative 37 (14%) (Scheme 7, path a). When
Bartonꢃs decarboxylation protocol [33] was used on the previously synthesized acid
chloride, only exocyclic alkene 34 and a thioether, 38, were obtained. Oxidation and
heating of compound 38 led to product 34 as the sole product.
The reactivity of the trans-decalin 32 was also studied (Scheme 8). Thus, reduction
of compound 32 with NaBH4 in i-PrOH for 2 h led to product 39, which can be used to
semisynthesize warburganal [34][35] and (ꢀ)-Ambroxꢂ [36][37]. Therefore, com-
pound 39 was treated with TsCl in pyridine to convert the OH group into a good leaving
group, but under these reaction conditions, only the conjugated diene 40 [14] was
obtained through elimination. Therefore, to carry out a SN reaction on the OH group,
the trifluoroacetate 41 was formed, but its treatment with KCN led to product 40 again.
However, when trifluoroacetate 41 was treated with Me3SiCN/BF3 ·Et2O in CH2Cl2 at

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Scheme 6. Oxidative Cleavage of trans-Triene 21
a) 1. O3, AcOEt, ꢀ788, 2 min; 2. Me2S, r.t., 12 h; 12 (28%) and 13 (41%). b) RuCl3, NaIO4, acetone,
H2O, r.t., 30 min; 32 (32%) and 33 (42%).
ꢀ108 the desired cyano derivative 42 and the diene 40 were obtained. Treatment of the
nitrile compound 42 with DIBALH followed by reduction with NaBH4 rendered
product 43 [38], which was cyclized under acidic conditions to (ꢀ)-Ambroxꢂ [39].
Scheme 7. Decarboxylation of Fragment 12
a) Pb(OAc)4, Cu(OAc)2, benzene/pyridine 3 :1, reflux, 2 h; 34 (33%), 35 (22%), 36 (11%), and 37
(14%). b) (COCl)2, CH2Cl2, r.t., 12 h. c) Pyridine-2-thiol N-oxide, pyridine, 4-(dimethylamino)pyridine
(DMAP), benzene, reflux, 2 h; 34 (12%), 38 (24%). d) MCPBA, CH2Cl2, ꢀ808, 3 h. e) D, 80 %.

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Scheme 8. Reactions of Fragment 32
a) NaBH4, i-PrOH, r.t., 2 h, 94%. b) TsCl, pyridine, r.t., 1 h, 72%. c) (CF3CO)2O, CH2Cl2/pyridine 3 :1,
ꢀ208, 3 h, 99%. d) KCN, 1308, 3 h, 69%. e) Me3SiCN/BF3 ·Et2O, CH2Cl2, ꢀ108, 1 h; 40 (23%) and 42
(58%). f) 1. Diisobutylaluminium hydride (DIBALH), toluene, ꢀ788, 1.5 h; 2. NaBH4, i-PrOH, r.t., 2 h,
78%. g) According to [39].
It has been previously commented that the bicyclic cis-decalin system derived from
the D- and E-rings is associated with skeletons of irregular triterpenes such as
camelliols A and B, as well as other tetracyclic (seco-C-oleanane) and bicyclic ones
(preoleanatetraene). A synthesis of a common bicyclic precursor for these compounds
was developed from compound 33, which only requires deoxygenation at C(15)
(Scheme 9). First, compound 33 was treated with NaBH4 in i-PrOH for the selective
reduction of the aldehyde of C(12). Then, the new OH group was protected with tert-
butyldimethylsilane chloride, providing with a good yield the corresponding derivative
45. The subsequent reduction of the ester group of 45 with LiAlH4 unexpectedly
eliminated the protecting group, forming diol 46. Therefore, a tetrahydropyranyl
protecting group was introduced by treatment with DHP/TsOH (intermediate 47), and
reduction of 47 with LiAlH4 in THF at room temperature led to compound 48. The OH
group at C(15) of 48 was eliminated through the xanthate intermediate 49, which was
treated with hypophosphorous acid to reduce the xanthate group and deprotect the OH
group and to give the desired final compound 50 [40].
Conclusions. – In summary, with these processes the environmental impact of the
solid waste from olive-oil industry is reduced, and several high added value bioactive

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Scheme 9. Reactions of Fragment 33
a) NaBH4, i-PrOH, r.t., 3 h, 98%. b) (t-Bu)Me2SiCl (TBDMSCl), pyridine, r.t., 12 h, 89%. c) LiAlH4,
THF, reflux, 1 h, 78%. d) 3,4-Dihydro-2H-pyran (DHP), TsOH, CH2Cl2, r.t., 1.5 h. e) LiAlH4, THF, r.t.,
3h. f) 1. NaH, THF, reflux, 3 h; 2. CS2, reflux, 30 min; 3. MeI, reflux, 1 h. g) H3PO2, AIBN, Et3N, dioxane,
reflux, 3 h, 58% (from 44).
compounds were obtained. Thus, methyl olean-12-en-28-oate (5) with several triene
systems in the C-ring was used as the starting material in different oxidative processes
to fragment the triterpene skeleton into several useful trans- and cis-decalin fragments.
In this sense, a homodiene (6) in the C-ring was formed by a spontaneous bromination/
dehydrobromination process, and several trans- and cis-triene compounds (8, 9, 21, and
22) were formed from this ring by chemical and photolytic isomerizations. The
treatment of the cis-triene 8 with several oxidative agents gave different oxidized
triterpene products, but in all of them, the central C¼C bond in (Z)-disposition was
unaffected. Ozonolysis of the exocyclic triene 9 rendered 16-carbon fragments and nor-
sesquiterpene compounds. In turn, oxidation of the trans-triene 21 with NaIO4/RuCl3
yielded two aldehyde sesquiterpenes by cleavage of the C¼C bond of the opened C-
ring. On the other hand, the reactivity of several sesquiterpene fragments was studied,
and a suitable approximation to the synthesis of interesting lower-molecular-weight
compounds was performed. Decarboxylation of the monocyclic fragment 12 gave
synthons related to mono- and tricyclic triterpenes such as elengasidiol, achilleols A
and B, and camelliol A. Moreover, the trans-decalin fragment 32, formed from the A-
and B-rings, was used as appropriate chiral synthon for the semisynthesis of products
related to drimane and ambra oxide. Finally, deoxygenation of the cis-decalin fragment
33, from the D- and E-rings of the original triterpene molecule, afforded a common
bicyclic precursor for the skeleton of bicyclic, tetracyclic, and irregular triterpenes.
´
This work was supported by a grant from the Comision Interministerial de Ciencia y Tecnologia and
by a project from the Ministerio de Educacion y Cultura. We thank David Nesbitt for reviewing the
manuscript concerning the English language.

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Experimental Part
General. Flash chromatography (FC): silica gel (SiO2; 40–60 mm); eluents: CH2Cl2 or CHCl3,
containing increasing amounts of Me2CO (from 100 :1 to 1:1), as well as mixtures of hexane/AcOEt
(from 40 :1 to 1:1). TLC: SiO2-coated plates; visualization by spraying with H2SO4/AcOH, followed by
heating to 1208. M.p.: Kofler apparatus; uncorrected. Optical rotations: Perkin-Elmer 341 polarimeter at
258. IR Spectra: Mattson Satellite FT-IR spectrometer. NMR Spectra (300.13 MHz for 1H, and
75.47 MHz for 13C): in CDCl3 on a Bruker AM-300 spectrometer; assignments of 13C chemical shifts by
DEPTusing a flip angle of 1358; NOE experiments by irradiation for four seconds in series of eight scans.
HR-MS: Micromass Autospec-Q spectrometer (EBE geometry).
Maslinic Acid (¼(2a,3b)-2,3-Dihydroxyolean-12-en-28-oic Acid; 2). Maslinic acid (2) was isolated
from the solid waste of olive-oil pressing which was extracted in a Soxhlet apparatus with AcOEt. It was
purified from these mixtures by CC over SiO2 and transformed with ethereal CH2N2 or NaOH/MeI into
the corresponding methyl ester which was deoxygenated in the A-ring to obtain methyl olean-12-en-28-
oate (5) [18].
Methyl Oleana-9(11),12-dien-28-oate (6). Compound 5 (450 mg, 1 mmol) was dissolved in CCl4
(15 ml), and NBS (212 mg, 1.2 mmol) and a cat. amount of AIBN were added. After 15 min under reflux,
the mixture was washed with sat. aq. soln. of NaHCO3 and extracted with CH2Cl2. The org. layer was
dried (Na2SO4), evaporated to dryness, and chromatographed on a SiO2 column to obtain 6 (370 mg,
83%) and methyl (4aS,6bR,8aS,12aS,14R,14aS,14bR)-14-bromo-1,3,4,5,6b,7,8,8a,9,10,11,12,12a,12b,
13,14,14a,14b-octadecahydro-2,2,6b,9,9,12a,14a-heptamethylpicene-4a(2H)-carboxylate (7; 53 mg, 10%).
Data of 6. White solid. M.p. 131–1338. [a]2D0 ¼ þ25 (c¼1, CHCl3). IR (CHCl3): 2947, 1728, 1462,
1163. 1H-NMR (300 MHz, CDCl3): 5.57 (d, J¼5.9, 1 H), 5.54 (d, J¼5.9, 1 H); 3.63 (s, 3 H); 3.00 (dd, J¼
3.7, 13.7, 1 H); 1.14 (s, 3 H); 1.01 (s, 3 H); 0.93 (s, 3 H); 0.92 (s, 3 H); 0.88 (s, 3 H); 0.88 (s, 3 H); 0.82 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 18.6 (CH2); 19.2 (CH2); 20.3 (Me); 20.4 (Me); 21.9 (Me); 23.7 (Me);
23.9 (CH2); 25.1 (Me); 27.0 (CH2); 30.7 (C); 32.1 (CH2); 32.3 (CH2); 33.0 (Me); 33.5 (Me); 33.5 (C); 33.9
(CH2); 38.9 (CH2); 39.1 (C); 39.7 (CH); 40.8 (C); 41.6 (CH2); 42.5 (C); 46.0 (CH2); 46.2 (C); 51.7 (Me);
51.9 (CH); 115.2 (CH); 120.7 (CH); 144.8 (C); 155.4 (C); 178.3 (C). HR-MS: 452.3655 (Mþ, C31H48O2þ ;
calc. 452.3649).
Data of 7. Colorless oil. [a]2D0 ¼ þ13 (c¼1, CHCl3). IR (CHCl3): 3443, 2947, 1727, 1462, 1163.
1H-NMR (300 MHz, CDCl3): 5.66 (dd, J¼3.3, 7.7, 1 H); 4.86 (dd, J¼9.1, 9.1, 1 H); 3.55 (s, 3 H); 2.71 (dd,
J¼6.0, 13.5, 1 H); 1.09 (s, 3 H); 0.97 (s, 3 H); 0.92 (s, 3 H); 0.87 (s, 3 H); 0.84 (s, 3 H); 0.82 (s, 3 H); 0.79
(s, 3 H). 13C-NMR (75 MHz, CDCl3): 15.6 (Me); 18.4 (CH2); 19.1 (CH2); 20.6 (Me); 21.5 (Me); 25.8
(Me); 27.7 (Me); 29.3 (CH2); 30.9 (C); 31.9 (CH2); 32.3 (Me); 32.5 (CH2); 33.2 (C); 33.3 (CH2); 34.0
(Me); 37.1 (CH2); 38.2 (C); 39.5 (CH2); 39.9 (C); 41.2 (CH); 41.5 (CH2); 42.0 (CH2); 43.7 (C); 51.2 (C);
51.6 (Me); 51.6 (CH); 56.6 (CH); 66.7 (CH); 121.3 (CH); 157.9 (C); 178.3 (C). HR-MS: 533.3001 (Mþ,
C31H49BrOþ2 ; calc. 533.2910).
Methyl (11Z)-8,14-Secoolea-8,11,13-trien-28-oate (¼ Methyl (4aS,8aS)-1,3,4,5,6,8a-Hexahydro-2,2,7-
trimethyl-8-{(Z)-2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethenyl}-
naphthalene-4a(2H)-carboxylate; 8). Compound 6 (365 mg, 0.8 mmol) was dissolved in EtOH (70 ml)
and irradiated in a borosilicate flask using a 125 W high-pressure Hg street lamp with the outermost glass
shell removed. After 30 min, the soln. was evaporated and the residue chromatographed on a SiO2
column to obtain 8 (175 mg, 46%) and methyl (4aS,8aS)-1,3,4,5,6,8a-hexahydro-2,2,7-trimethyl-8-{(2E)-2-
[(4aS,8aS)-octahydro-5,5,8a-trimethyl-2-methylidenenaphthalen-1(2H)-ylidene]ethyl}naphthalene-
4a(2H)-carboxylate (9, 137 mg, 38%). Compound 9 could be also obtained from 8 (363 mg, 0.8 mmol)
when 8 was dissolved in EtOH (70 ml) and irradiated in a quartz flask using a 125 W high-pressure Hg
street lamp with the outermost glass shell removed. After 1 h, the soln. was evaporated and the residue
chromatographed on a SiO2 column to obtain 9 (344 mg, 95%).
Data of 8. Colorless oil. [a]2D0 ¼ þ179 (c¼1, CHCl3). IR (CHCl3): 2945, 1731, 1461, 1249, 1169.
1H-NMR (300 MHz, CDCl3): 5.97 (d, J¼12.9, 1 H); 5.83 (d, J¼12.9, 1 H); 3.61 (s, 3 H); 2.79 (dd, J¼3.6,
12.5, 1 H); 1.49 (s, 3 H); 1.25 (s, 3 H); 1.01 (s, 3 H); 0.89 (s, 3 H); 0.89 (s, 3 H); 0.86 (s, 3 H); 0.85 (s, 3 H).
13C-NMR (CDCl3): 19.2 (CH2); 19.3 (CH2); 20.9 (Me); 21.6 (Me); 21.8 (Me); 22.0 (Me); 22.8 (CH2); 25.0
(Me); 29.8 (CH2); 29.8 (CH2); 30.8 (C); 32.9 (CH2); 33.0 (Me); 33.5 (Me); 33.5 (C); 34.1 (CH2); 37.2

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CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
(CH); 38.0 (CH2); 38.9 (C); 41.8 (CH2); 43.0 (CH2); 45.5 (C); 51.5 (CH); 51.7 (Me); 127.7 (CH); 127.7
(C); 129.5 (C); 132.4 (CH); 134.6 (C); 138.8 (C); 178.4 (C). HR-MS: 475.3555 ([MþNa]þ
,
C31H48NaOþ2 ; calc. 475.3552).
Data of 9. Colorless oil. [a]2D0 ¼ þ42 (c¼1, CHCl3). IR (CHCl3): 2949, 1730, 1462, 1253, 1168.
1H-NMR (300 MHz, CDCl3): 4.98 (d, J¼2.5, 1 H); 4.94 (dd, J¼4.5, 9.4, 1 H); 4.52 (d, J¼2.5, 1 H); 3.62
(s, 3 H); 1.52 (s, 3 H); 0.94 (s, 3 H); 0.91 (s, 3 H); 0.88 (s, 3 H); 0.86 (s, 3 H); 0.85 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 19.0 (Me); 19.4 (CH2); 20.7 (Me); 22.1 (Me); 23.1 (CH2); 23.7 (CH2); 24.3 (Me); 29.9
(CH2); 30.6 (CH2); 30.7 (C); 32.2 (CH2); 33.0 (Me); 33.6 (Me); 34.0 (C); 34.1 (CH2); 36.1 (CH); 37.5
(CH2); 37.6 (CH2); 40.8 (C); 41.6 (CH2); 42.6 (CH2); 45.8 (C); 51.7 (Me); 53.6 (CH); 111.6 (CH2); 116.7
(CH); 124.9 (C); 133.7 (C); 146.1 (C); 151.8 (C); 178.4 (C). HR-MS: 475.3551 ([MþNa]þ
,
C31H48NaOþ2 ; calc. 475.3552).
Methyl 8a,14a-Dihydroxy-9b,13b-oxy-8,14-secoolean-11-en-28-oate (¼ Methyl (1S,4aS,4a’’S,5’R,8aR,
8a’’S)-3,3’’,4,4’’,4a’’,5’’,6,6’’,7,7’’,8,8’’,8a,8a’’-Tetradecahydro-2,2’’-dihydroxy-2,2’’,5’’,5’’,7,7,8a’’-heptamethyl-
2H,2’’H-dispiro[naphthalene-1,2’-furan-5’,1’’-naphthalene]-4a(5H)-carboxylate; 10). NaIO4 (189 mg,
0.88 mmol) and RuCl3 ·3 H2O (ca. 5 mg) in H2O (2 ml) was added to a soln. of product 8 (100 mg,
0.22 mmol) in acetone (10 ml). The mixture was stirred at r.t. for 30 min, and then diluted with CH2Cl2.
The org. layer was washed with H2O and dried (Na2SO4). The soln. was evaporated at reduced pressure,
and the residue was chromatographed on a SiO2 column to yield 10 (88 mg, 80%). Colorless oil. [a]2D0 ¼ þ
16 (c¼1, CHCl3). IR (CHCl3): 2946, 1724, 1057, 767. 1H-NMR (300 MHz, CDCl3): 5.70 (d, J¼6.4, 1 H);
5.51 (d, J¼6.4, 1 H); 3.67 (s, 3 H); 2.89 (dd, J¼4.3, 13.7, 1 H); 1.30 (s, 3 H); 1.22 (s, 3 H); 1.01 (s, 3 H);
0.98 (s, 3 H); 0.92 (s, 3 H); 0.89 (s, 3 H); 0.82 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 18.5 (CH2); 19.7
(Me); 20.1 (CH2); 22.1 (Me); 23.2 (CH2); 24.0 (Me); 26.9 (Me); 29.3 (Me); 30.4 (C); 33.5 (Me); 33.6
(Me); 34.2 (CH2); 34.5 (CH2); 35.0 (CH2); 36.0 (CH2); 38.7 (CH2); 39.9 (CH2); 41.9 (CH2); 33.9 (C); 42.7
(C); 42.9 (CH); 47.0 (C); 47.1 (CH); 52.0 (Me); 74.2 (C); 74.6 (C); 95.6 (C); 103.6 (C); 124.8 (CH); 134.5
(CH); 179.5 (C). HR-MS: 525.3556 ([MþNa]þ , C31H50NaO5þ ; calc. 525.3556).
Methyl 8,9-Dioxo-(8,9),(8,14)-disecooleana-11,13-dien-28-oate (¼ Methyl (4aS,8aS)-1,3,4,5,6,8a-
Hexahydro-2,2,7-trimethyl-8-{(1Z)-3-oxo-3-[(1S,2S)-1,3,3-trimethyl-2-(3-oxobutyl)cyclohexyl]prop-1-
en-1-yl}naphthalene-4a(2H)-carboxylate; 11). Compound 8 (285 mg, 0.63 mmol) was dissolved in AcOEt
(10 ml), stirred at ꢀ788, and an O3 flow lower than 0.1 l/min (50% O2/50% O3) was passed through the
soln. After 7 min, Me2S (0.5 ml) was added. The mixture was maintained under stirring while being
cooled for 1 h. Then, it was evaporated and purified over SiO2 to yield 11 (37 mg, 12%), (1S,2S)-1,3,3-
trimethyl-2-(3-oxobutyl)cyclohexanecarboxylic acid (12; 17 mg, 22%), methyl (1aS,3aS,7aR,7bR)-7b-
formyloctahydro-1a,6,6-trimethylnaphtho[1,2-b]oxirene-3a(1aH)-carboxylate (13, 22 mg, 25%), and
(2S,4aS,8aR)-hexahydro-2-hydroxy-2,7,7-trimethyl-9-oxo-2H-1,4a-(epoxymethano)naphthalene-1(5H)-
carbaldehyde (14, 12 mg, 14%).
1
Data of 11. Colorless oil. [a]2D0 ¼ þ99 (c¼1, CHCl3). IR (CHCl3): 2925, 2854, 1698, 773. H-NMR
(300 MHz, CDCl3): 7.72 (d, J¼15.4, 1 H); 6.64 (d, J¼15.4, 1 H); 3.60 (s, 3 H); 3.15 (dd, J¼3.6, 13.9,
1 H); 2.00 (s, 3 H); 1.24 (s, 3 H); 1.19 (s, 3 H); 1.09 (s, 3 H); 0.94 (s, 3 H); 0.93 (s, 3 H); 0.92 (s, 3 H).
13C-NMR (75 MHz, CDCl3): 18.4 (CH2); 19.6 (Me); 21.9 (CH2); 22.1 (CH2); 22.5 (Me); 24.2 (Me); 29.8
(CH2); 29.9 (Me); 31.0 (C); 31.7 (CH2); 32.0 (CH2); 32.9 (Me); 33.4 (Me); 33.6 (Me); 34.0 (CH2); 34.5
(CH); 36.5 (CH2); 41.6 (C); 42.2 (CH2); 45.2 (CH2); 45.5 (C); 48.0 (CH); 51.8 (C); 52.0 (Me); 118.2
(CH); 132.0 (C); 139.8 (CH); 142.6 (C); 177.8 (C); 205.7 (C); 208.7 (C). HR-MS: 507.3458 ([MþNa]þ
,
C31H48NaOþ4 ; calc. 507.3450).
1
Data of 12. Colorless oil. [a]2D0 ¼ þ1 (c¼1, CHCl3). IR (CHCl3): 2925, 2854, 1698, 773. H-NMR
(300 MHz, CDCl3): 2.11 (s, 3 H); 1.23 (s, 3 H); 0.96 (s, 3 H); 0.93 (s, 3 H). 13C-NMR (75 MHz, CDCl3):
17.5 (Me); 18.3 (CH2); 22.1 (CH2); 22.6 (Me); 29.9 (Me); 33.2 (Me); 34.4 (C); 37.5 (CH2); 41.1 (CH2);
45.2 (CH2); 47.3 (C); 48.8 (CH); 184.2 (C); 208.9 (C). HR-MS: 263.1629 ([MþNa]þ , C14H24NaO3þ ; calc.
263.1623).
Data of 13. Colorless oil. [a]2D0 ¼ þ34 (c¼1, CHCl3). IR (CHCl3): 3497, 2948, 1759, 1724, 1465, 1079.
1H-NMR (300 MHz, CDCl3): 9.41 (s, 1 H); 3.72 (s, 3 H); 3.25 (ddd, J¼1.7, 4.8, 12.9, 1 H); 1.34 (s, 3 H);
0.96 (s, 3 H); 0.94 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 19.2 (Me); 23.0 (CH2); 24.0 (Me); 28.5 (Me);
29.7 (C); 30.1 (CH2); 30.7 (CH2); 32.6 (Me); 33.9 (CH2); 36.4 (CH2); 43.7 (C); 51.9 (CH); 64.8 (C); 70.1
(C); 177.4 (C); 200.1 (CH). HR-MS: 303.1568 ([MþNa]þ , C16H24NaO4þ ; calc. 303.1572).

CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
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Data of 14. White solid. M.p. 97–998. [a]D20 ¼ þ63 (c¼1, CHCl3). IR (CHCl3): 3477, 1745, 1708, 1077,
772. 1H-NMR (300 MHz, CDCl3): 9.50 (d, J¼1.5, 1 H); 3.54 (d, J¼1.5, 3 H); 1.21 (s, 3 H); 1.03 (s, 3 H);
0.94 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 20.4 (Me); 20.5 (CH2); 24.1 (Me); 26.9 (CH2); 28.8 (CH2);
30.3 (C); 33.1 (Me); 33.1 (CH2); 33.2 (CH2); 34.7 (CH); 39.8 (C); 79.2 (C); 82.5 (C); 177.5 (C); 200.0
(CH). HR-MS: 289.1480 ([MþNa]þ , C15H22NaOþ4 ; calc. 289.1416).
Methyl 8a,9a-Epoxy-8,14-secooleana-11,13-dien-28-oate (¼ Methyl (4aS,8aS)-1,3,4,5,6,8a-Hexahy-
dro-2,2,7-trimethyl-8-{(Z)-2-[(1aR,7aS,7bS)-octahydro-1a,4,4,7a-tetramethylnaphtho[1,2-b]oxiren-
7b(1aH)-yl]ethenyl}naphthalene-4a(2H)-carboxylate; 15). Product 8 (100 mg, 0.5 mmol) was dissolved in
CH2Cl2 (10 ml), and MCPBA (130 mg, 0.75 mmol) was added. The mixture was stirred at different
temps. (Table). To stop the reaction, the mixture was diluted with CH2Cl2, and the org. layer was washed
with sat. aq. soln. of FeSO4, neutralized with sat. aq. soln. of NaHCO3, dried (Na2SO4), filtered, and the
soln. was evaporated to dryness. Depending on the reaction conditions (Table) and after chromatography
on SiO2 , different amounts of 15, methyl (3aS,7aR,7bR)-octahydro-1a,6,6-trimethyl-7b-{(Z)-2-
[(1aR,7aS,7bS)-octahydro-1a,4,4,7a-tetramethylnaphtho[1,2-b]oxiren-7b(1aH)-yl]ethenyl}naphtho[1,2-
b]oxirene-3a(1aH)-carboxylate (16), methyl (3aS,7aR,7bS)-octahydro-1a,6,6-trimethyl-7b-{(Z)-2-
[(1aR,7aS,7bS)-octahydro-1a,4,4,7a-tetramethylnaphtho[1,2-b]oxiren-7b(1aH)-yl]ethenyl}naphtho[1,2-
b]oxirene-3a(1aH)-carboxylate (17), (1S,4aS,8aR)-octahydro-2-hydroxy-2,7,7-trimethyl-1-{(Z)-2-
[(1aR,7aS,7bS)-octahydro-1a,4,4,7a-tetramethylnaphtho[1,2-b]oxiren-7b(1aH)-yl]ethenyl}-2H-1,4a-(ep-
oxymethano)naphthalen-9-one (18), methyl (1S,4aS,8aR)-octahydro-1,2-dihydroxy-2,7,7-trimethyl-1-
{(Z)-2-[(1aR,7aS,7bS)-octahydro-1a,4,4,7a-tetramethylnaphtho[1,2-b]oxiren-7b(1aH)-yl]ethenyl}naph-
thalene-4a(2H)-carboxylate (19), and methyl (1S,4aS,5’S,8aR,8a’’S)-3,4,4a’’,5’’,6,6’’,7,7’’,8,8’’,8a,8a’’-do-
decahydro-2-hydroxy-2,2’’,5’’,5’’,7,7,8a’’-heptamethyl-2H,4’’H-dispiro[naphthalene-1,2’-furan-5’,1’’-naph-
thalene]-4a(5H)-carboxylate (20) were obtained.
1
Data of 15. Colorless oil. [a]2D0 ¼ þ27 (c¼1, CHCl3). IR (CHCl3): 2945, 772. H-NMR (300 MHz,
CDCl3): 6.10 (d, J¼13.3, 1 H); 5.60 (d, J¼13.3, 1 H); 3.70 (s, 3 H); 3.50 (dd, J¼3.5, 13.0, 1 H); 1.50 (s,
3 H); 1.20 (s, 3 H); 1.10 (s, 3 H); 0.88 (s, 3 H); 0.83 (s, 3 H); 0.80 (s, 3 H); 0.78 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 17.3 (CH2); 18.4 (Me); 18.6 (CH2); 20.8 (Me); 21.6 (Me); 22.4 (Me); 23.6 (CH2); 25.0
(Me); 28.5 (CH2); 29.5 (CH2); 30.7 (C); 32.0 (CH2); 32.5 (Me); 33.1 (Me); 33.8 (Me); 34.5 (CH2); 35.2
(CH2); 36.1 (CH); 38.6 (C); 41.6 (CH2); 41.9 (CH); 42.8 (CH2); 45.2 (C); 51.8 (Me); 60.7 (C); 72.1 (C);
126.6 (CH); 127.5 (C); 132.7 (C); 134.4 (CH); 178.6 (C). HR-MS: 491.3506 ([MþNa]þ , C31H48NaO3þ ;
calc. 491.3501).
1
Data of 16. Colorless oil. [a]2D0 ¼ þ33 (c¼1, CHCl3). IR (CHCl3): 2946, 772. H-NMR (300 MHz,
CDCl3): 5.89 (d, J¼13.6, 1 H); 5.66 (d, J¼13.6, 1 H); 3.68 (s, 3 H); 2.49 (dd, J¼3.3, 13.6, 1 H); 1.11 (s,
3 H); 1.10 (s, 6 H); 0.95 (s, 3 H); 0.86 (s, 3 H); 0.81 (s, 6 H). 13C-NMR (75 MHz, CDCl3): 17.2 (CH2); 18.4
(CH2); 18.7 (Me); 20.4 (Me); 20.9 (Me); 21.4 (Me); 22.6 (CH2); 24.0 (Me); 28.4 (CH2); 29.5 (CH2); 30.0
(C); 31.5 (CH2); 33.1 (Me); 33.1 (C); 33.6 (Me); 34.2 (CH2); 34.8 (CH2); 35.9 (CH); 37.3 (CH2); 37.4 (C);
41.5 (CH); 41.8 (CH2); 45.5 (C); 51.7 (Me); 61.1 (C); 62.4 (C); 65.5 (C); 72.1 (C); 125.8 (CH); 132.7
(CH); 178.4 (C). HR-MS: 507.3452 ([MþNa]þ , C31H48NaO4þ ; calc. 507.3450).
Data of 17. Colorless oil. [a]2D0 ¼ þ25 (c¼1, CHCl3). IR (CHCl3): 3409, 2940, 769. 1H-NMR
(300 MHz, CDCl3): 5.85 (d, J¼12.3, 1 H); 5.68 (d, J¼12.3, 1 H); 3.76 (s, 3 H); 3.27 (dd, J¼4.1, 13.5,
1 H); 1.17 (s, 3 H); 1.11 (s, 3 H); 1.06 (s, 3 H); 0.90 (s, 3 H); 0.88 (s, 3 H); 0.78 (s, 6 H). 13C-NMR
(75 MHz, CDCl3): 17.4 (CH2); 18.6 (CH2); 18.7 (Me); 19.8 (CH2); 21.6 (Me); 21.7 (Me); 21.8 (Me); 24.9
(Me); 25.7 (CH2); 28.9 (CH2); 29.8 (CH2); 30.5 (C); 31.9 (CH2); 33.0 (C); 33.1 (Me); 33.6 (CH2); 33.9
(Me); 36.8 (CH); 37.9 (C); 38.3 (CH2); 41.5 (CH2); 41.9 (CH); 42.6 (C); 51.4 (Me); 57.3 (C); 59.9 (C);
66.3 (C); 72.5 (C); 130.3 (CH); 178.6 (C). HR-MS: 507.3498 ([MþNa]þ , C31H48NaO4þ ; calc. 507.3450).
Data of 18. Colorless oil. [a]2D0 ¼ þ38 (c¼1, CHCl3). IR (CHCl3): 2866, 1750, 1457, 1082. 1H-NMR
(CDCl3): 6.03 (s, 1 H); 5.80 (d, J¼14.1, 1 H); 5.59 (d, J¼14.1, 1 H); 1.25 (s, 3 H); 1.25 (s, 3 H); 1.11 (s,
3 H); 0.95 (s, 3 H); 0.83 (s, 3 H); 0.82 (s, 3 H). 13C-NMR (CDCl3): 16.8 (CH2); 18.3 (CH2); 18.6 (Me);
20.5 (CH2); 20.6 (Me); 20.9 (Me); 21.2 (Me); 21.5 (Me); 24.2 (Me); 27.1 (CH2); 27.8 (CH2); 28.4 (CH2);
30.5 (C); 33.1 (C); 33.3 (CH2); 33.6 (Me); 37.4 (C); 37.5 (CH2); 40.6 (C); 41.6 (CH2); 41.8 (CH); 42.2
(CH); 67.1 (C); 74.5 (C); 74.7 (C); 84.7 (C); 121.1 (CH); 137.9 (CH); 179.0 (C). HR-MS: 493.3267 ([Mþ
Na]þ , C30H46NaOþ4 ; calc. 493.3294).

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CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
1
Data of 19. Colorless oil. [a]2D0 ¼ þ33 (c¼1, CHCl3). IR (CHCl3): 2946, 772. H-NMR (300 MHz,
CDCl3): 6.07 (d, J¼13.7, 1 H); 5.71 (d, J¼13.7, 1 H); 4.65 (br. s, 1 H); 3.71 (s, 3 H); 2.59 (dd, J¼3.2, 13.7,
1 H); 1.24 (s, 6 H); 1.12 (s, 3 H); 1.11 (s, 3 H); 0.86 (s, 3 H); 0.80 (s, 3 H); 0.79 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 17.0 (CH2); 18.6 (CH2); 18.8 (Me); 21.6 (Me); 21.9 (Me); 22.2 (CH2); 23.5 (Me); 27.4
(Me); 28.4 (CH2); 29.7 (CH2); 30.7 (C); 33.0 (C); 33.3 (Me); 33.7 (CH2); 34.1 (CH2); 36.2 (CH2); 37.6
(C); 37.9 (CH2); 41.3 (CH2); 41.6 (CH); 44.1 (C); 45.2 (CH); 51.4 (Me); 65.3 (C); 73.9 (C); 74.3 (C); 77.7
(CH); 123.4 (CH); 136.8 (CH); 179.7 (C). HR-MS: 525.3552 ([MþNa]þ , C31H50NaO5þ ; calc. 525.3556).
Data of 20. Colorless oil. [a]2D0 ¼ ꢀ43 (c¼1, CHCl3). IR (CHCl3): 2946, 1715, 771. 1H-NMR
(300 MHz, CDCl3): 6.11 (d, J¼6.3, 1 H); 5.89 (d, J¼6.3, 1 H); 5.55 (dd, J¼3.5, 5.0, 1 H); 3.50 (s, 3 H);
2.70 (dd, J¼3.2, 12.1, 1 H); 2.29 (ddd, J¼3.7, 13.4, 13.9, 1 H); 1.67 (s, 3 H); 1.17 (s, 3 H); 0.88 (s, 3 H);
0.87 (s, 6 H); 0.85 (s, 3 H); 0.83 (s, 3 H): 13C-NMR (75 MHz, CDCl3): 18.7 (Me); 18.7 (CH2); 21.2 (Me);
22.7 (CH2); 23.5 (Me); 23.7 (Me); 25.3 (CH2); 29.8 (C); 30.8 (C); 31.4 (Me); 32.6 (Me); 33.4 (Me); 33.8
(CH2); 34.2 (CH2); 34.3 (CH2); 34.9 (CH2); 38.5 (CH2); 40.9 (CH); 41.1 (C); 42.4 (CH2); 44.2 (CH); 45.0
(C); 51.6 (Me); 74.9 (C); 93.7 (C); 97.1 (C); 127.1 (CH); 131.5 (CH); 132.5 (CH); 133.9 (C); 179.0 (C).
HR-MS: 507.3444 ([MþNa]þ , C31H48NaO4þ ; calc. 507.3450).
Methyl (11E)-8,14-Secoolea-8,11,13-trien-28-oate (¼ Methyl (4aS,8aS)-1,3,4,5,6,8a-Hexahydro-2,2,7-
trimethyl-8-{(E)-2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethenyl}-
naphthalene-4a(2H)-carboxylate; 21). I2 (5 mg, 0.02 mmol) was added to a soln. of 8 (50 mg, 0.1 mmol) in
hexane (50 ml). After 5 h at reflux, 0.5 ml of sat. aq. soln. of NaHSO4 was added, and the mixture was
diluted with CH2Cl2. The org. layer was washed with H2O, dried (Na2SO4), and evaporated to dryness.
Chromatography on a SiO2 column yielded 21 (30 mg, 65%). Colorless oil. [a]2D0 ¼ þ57 (c¼1, CHCl3).
IR (CHCl3): 2946, 1729, 1462, 1170, 757. 1H-NMR (300 MHz, CDCl3): 6.15 (d, J¼16.2, 1 H); 5.99 (d, J¼
16.2, 1 H); 3.61 (s, 3 H); 3.14 (dd, J¼3.4, 13.0, 1 H); 1.67 (s, 3 H); 1.64 (s, 3 H); 1.01 (s, 3 H); 1.00 (s, 3 H);
0.88 (s, 3 H); 0.88 (s, 3 H); 0.84 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 19.0 (Me); 19.0 (CH2); 19.2 (CH2);
20.4 (Me); 21.5 (Me); 21.7 (Me); 22.5 (CH2); 24.1 (Me); 30.6 (CH2); 30.9 (C); 32.1 (CH2); 32.9 (CH);
33.3 (Me); 33.4 (Me); 33.4 (C); 33.7 (CH2); 34.2 (CH2); 38.3 (C); 38.5 (CH2); 41.9 (CH2); 42.2 (CH2);
45.7 (C); 51.4 (Me); 51.6 (CH); 123.7 (CH); 126.4 (C); 129.1 (C); 130.9 (CH); 132.6 (C); 142.3 (C); 178.2
(C). HR-MS: 452.3668 (Mþ, C31H48O2þ ; 452.3654).
Compound 21 could also be obtained by isomerization of 8 (200 mg, 0.44 mmol) dissolved in toluene
(20 ml) and treated with TFA (20 ml) for 3.5 h under reflux. This mixture was evaporated to dryness and
chromatographed over a SiO2 column to give 21 (190 mg, 95%).
Methyl 8,14-Secoolea-7,9(11),13-trien-28-oate (¼ Methyl (4aS,8aS)-1,3,4,5,6,8a-Hexahydro-2,2,7-tri-
methyl-8-{(2E)-2-[(4aS,8aS)-4a,5,6,7,8,8a-hexahydro-2,5,5,8a-tetramethylnaphthalen-1(4H)-ylidene]-
ethyl}naphthalene-4a(2H)-carboxylate; 22). Trifluoroacetic acid (10 ml) was added to a soln. of 8 (100 mg,
0.22 mmol) in CH2Cl2 (10 ml). After 5 h under reflux, the mixture was evaporated to dryness. CC over
SiO2 yielded 21 (15 mg, 15%) and 22 (80 mg, 80%). Colorless oil. [a]2D0 ¼ þ81 (c¼1, CHCl3). IR
(CHCl3): 3417, 2947, 1727, 1443, 1168. 1H-NMR (300 MHz, CDCl3): 6.10 (d, J¼11.1, 1 H); 5.49 (dd, J¼
1.8, 1.8, 1 H); 5.25 (dd, J¼11.7, 1 H); 3.67 (s, 3 H); 3.64 (d, J¼11.7, 1 H); 2.94 (dd, J¼12.6, 1 H); 1.64 (s,
3 H); 1.49 (s, 3 H); 0.90 (s, 3 H); 0.87 (s, 6 H); 0.87 (s, 3 H); 0.84 (s, 3 H); 0.80 (s, 3 H). 13C-NMR
(CDCl3): 14.6 (Me); 19.0 (CH2); 20.9 (Me); 22.2 (Me); 22.7 (CH2); 23.1 (Me); 24.2 (CH2); 24.7 (Me);
29.3 (CH2); 30.9 (C); 33.1 (Me); 33.3 (C); 33.6 (Me); 34.2 (CH2); 37.1 (C); 39.1 (CH); 39.5 (CH2); 42.7
(CH2); 42.8 (CH2); 45.7 (C); 49.7 (CH); 52.1 (CH); 53.0 (Me); 121.9 (CH); 128.4 (C); 132.1 (CH); 132.4
(C); 132.7 (CH); 134.1 (CH); 178.6 (C). HR-MS: 452.3663 (Mþ, C31H48O2þ ; calc. 452.3654).
(2R,4aS,8aS)-Octahydro-5,5,8a-trimethyl-1H-spiro[naphthalene-2,2’-oxiran]-1-one (23). Compound
9 (100 mg, 0.2 mmol) was dissolved in AcOEt (8 ml), and an O3 flow of 0.1 l/min (10% O2/90% O3) was
passed through the soln. for 2 min at ꢀ788. Then, Me2S (1 ml) was added, and the mixture was
maintained at r.t. during 12 h with stirring, evaporated to dryness, and purified over SiO2 to give 23
(12 mg, 24%), methyl (1aS,3aS,7aR,7bR)-octahydro-1a,6,6-trimethyl-7b-(2-oxoethyl)naphtho[1,2-b]ox-
irene-3a(1aH)-carboxylate (24, 10 mg, 32%) [18], and [(2S,4aS,8aR)-hexahydro-2-hydroxy-2,7,7-trimeth-
yl-9-oxo-2H-1,4a-(epoxymethano)naphthalen-1(5H)-yl]acetaldehyde (25, 5 mg, 16%).
Data of 23. Colorless oil. [a]2D0 ¼ þ10 (c¼1, CHCl3). IR (CHCl3): 2929, 1716, 1460, 1007, 907.
1H-NMR (300 MHz, CDCl3): 3.21 (d, J¼5.5, 1 H); 2.55 (d, J¼5.5, 1 H); 1.22 (s, 3 H); 0.96 (s, 3 H); 0.93
(s, 3 H). 13C-NMR (75 MHz, CDCl3): 17.5 (Me); 17.9 (CH2); 18.9 (CH2); 22.2 (Me); 31.5 (CH2); 33.2

CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
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(Me); 33.9 (CH2); 34.4 (C); 41.6 (CH2); 49.8 (C); 50.6 (CH2); 50.7 (CH); 58.0 (C); 210.8 (C). HR-MS:
245.1618 ([MþNa]þ , C14H22NaOþ2 ; calc. 245.1517).
Data of 25. Colorless oil. [a]2D0 ¼ þ13 (c¼1, CHCl3). IR (CHCl3): 2947, 1736, 1466, 1378, 1256, 1081.
1H-NMR (CDCl3): 9.07 (dd, J¼1.3, 1.3, 1 H); 2.82 (dd, J¼1.3, 17.2, 1 H); 2.74 (dd, J¼1.3, 17.2, 1 H); 2.03
(dd, J¼3.2, 17.6, 1 H); 1.32 (s, 3 H); 0.98 (s, 3 H); 0.84 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 20.6 (CH2);
20.6 (Me); 24.1 (Me); 26.8 (CH2); 27.4 (CH2); 29.8 (Me); 30.5 (C); 33.1 (CH2); 34.5 (CH2); 40.3 (C); 41.9
(CH); 50.7 (CH2); 74.3 (C); 83.6 (C); 178.3 (C); 203.8 (CH). HR-MS: 303.1573 ([MþNa]þ
,
C16H24NaOþ4 ; calc. 303.1572).
(1R,2R,4aS,8aS)-Octahydro-5,5,8a-trimethyl-1H-spiro[naphthalene-2,2’-oxiran]-1-ol (26). Com-
pound 9 (100 mg, 0.22 mmol) was dissolved in AcOEt (8 ml), stirred at ꢀ788, and an O3 flow lower
than 0.1 l/min (50% O2/50% O3) was passed through the soln. After 5 min, the mixture was evaporated.
The residue was redissolved in i-PrOH, NaBH4 (14 mg) was added, and the mixture stirred for 2 h at r.t.
The mixture was diluted with CH2Cl2, and the org. layer was washed with H2O, dried (Na2SO4),
evaporated to dryness, and purified over SiO2 to yield 26 (7 mg, 22%), (1R,2S,4aS,8aS)-octahydro-5,5,8a-
trimethyl-1H-spiro[naphthalene-2,2’-oxiran]-1-ol (27, 3 mg, 9%), and methyl (1aS,3aS,7aR,7bR)-octahy-
dro-7b-(2-hydroxyethyl)-1a,6,6-trimethylnaphtho[1,2-b]oxirene-3a(1aH)-carboxylate (28, 14 mg, 36%).
Data of 26. Colorless oil. [a]2D0 ¼ þ2 (c¼0.1, CHCl3). IR (CHCl3): 2926, 1718, 1459, 1085, 713.
1H-NMR (300 MHz, CDCl3): 3.28 (d, J¼11.1, 1 H); 2.87 (d, J¼4.9, 1 H); 2.32 (d, J¼4.9, 1 H); 0.91 (s,
3 H); 0.90 (s, 3 H); 0.88 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 13.0 (Me); 18.3 (CH2); 19.5 (CH2); 22.2
(Me); 32.7 (CH2); 33.2 (C); 33.6 (Me); 38.4 (CH2); 41.0 (C); 42.1 (CH2); 47.4 (CH2); 51.2 (CH); 58.5 (C);
77.2 (CH). HR-MS: 247.1766 ([MþNa]þ , C14H24NaO2þ ; calc. 247.1674).
Data of 27. White solid. M.p. 101–1038. [a]2D0 ¼ þ7 (c¼0.1, CHCl3). IR (CHCl3): 2923, 2854, 1743,
1
1701, 1654, 772. H-NMR (300 MHz, CDCl3): 3.35 (s, 1 H); 3.05 (dd, J¼1.8, 5.0, 1 H); 2.58 (d, J¼5.0,
1 H); 0.90 (s, 3 H); 0.88 (s, 3 H); 0.85 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 13.0 (Me); 18.4 (CH2); 21.3
(CH2); 21.9 (Me); 32.4 (CH2); 33.2 (C); 33.5 (Me); 38.4 (CH2); 40.9 (C); 42.1 (CH2); 51.0 (CH2); 52.3
(CH); 59.9 (C); 78.4 (CH). HR-MS: 247.1766 ([MþNa]þ , C14H24NaO2þ ; calc. 247.1674).
Data of 28. White solid. M.p. 90–928. [a]D20 ¼ ꢀ4 (c¼1, CHCl3). IR (CHCl3): 3421, 2949, 2864, 1731,
1457, 1253, 1038. 1H-NMR (300 MHz, CDCl3): 3.75–3.90 (m, 2 H); 3.68 (s, 3 H); 2.50 (dd, J¼5.9, 11.4,
1 H); 1.26 (s, 3 H); 0.92 (s, 3 H); 0.88 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 20.2 (Me); 23.1 (CH2); 24.1
(Me); 29.7 (C); 30.5 (CH2); 31.1 (CH2); 32.8 (Me); 33.5 (CH); 34.2 (CH2); 35.9 (CH2); 36.7 (CH2); 45.4
(C); 52.3 (Me); 59.8 (CH); 63.1 (C); 66.7 (C); 179.6 (C). HR-MS: 319.1890 ([MþNa]þ , C17H28NaO4þ ;
calc. 319.1885).
(1R,2S,4aS,8aS)-Decahydro-2,5,5,8a-tetramethylnaphthalene-1,2-diol (29). Compound 9 (76 mg,
0.22 mmol) was dissolved in AcOEt (10 ml), stirred at ꢀ788, and an O3 flow lower than 0.1 l/min
(50% O2/50% O3) was passed through the soln. After 5 min, the soln. was evaporated. The residue was
redissolved in THF, 2 ml of a 1m soln. of LiAlH4 in THF were added, and the mixture was stirred for 1 h at
reflux. After that, the mixture was diluted with CH2Cl2, and the org. layer was washed with H2O and
dried (Na2SO4). The soln. was evaporated to dryness, and the residue was purified over SiO2, yielding 29
(11 mg, 20%), (1R,2S,4aS,8aS)-decahydro-5,5,8a-trimethylnaphthalene-1,2-diol (30, 10 mg, 8%), and
(2S,4aS,8aR)-1-(2-hydroxyethyl)-octahydro-2,7,7-trimethyl-2H-1,4a-(epoxymethano)naphthalen-2-ol (31,
12 mg, 25%).
Data of 29. White solid. M.p. 97–998. [a]D20 ¼ ꢀ5 (c¼0.6, CHCl3). IR (CHCl3): 3410, 3284, 2927,
1063. 1H-NMR (300 MHz, CDCl3): 2.87 (s, 1 H); 1.20 (s, 3 H); 1.00 (s, 3 H); 0.87 (s, 3 H); 0.85 (s, 3 H).
13C-NMR (75 MHz, CDCl3): 13.6 (Me); 17.9 (CH2); 18.1 (CH2); 21.9 (Me); 29.6 (Me); 33.1 (C); 33.5
(Me); 38.8 (CH2); 39.1 (CH2); 39.9 (C); 42.0 (CH2); 53.1 (CH); 72.6 (C); 84.4 (CH). HR-MS: 249.1834
([MþNa]þ , C14H26NaOþ2 ; calc. 249.1830).
Data of 30. White solid. M.p. 160–1628. [a]2D0 ¼ ꢀ3 (c¼0.5, CHCl3). IR (CHCl3): 3432, 2924, 1461,
1044, 984. 1H-NMR (300 MHz, CDCl3): 3.96 (d, J¼2.9, 1 H); 3.10 (d, J¼2.9, 1 H); 1.04 (s, 3 H); 0.88 (s,
3 H); 0.86 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 14.3 (Me); 16.4 (CH2); 18.0 (CH2); 21.9 (Me); 32.1
(CH2); 33.0 (C); 33.5 (Me); 38.4 (CH2); 39.8 (C); 42.1 (CH2); 52.9 (CH); 70.6 (CH); 81.1 (CH). HR-MS:
235.1672 ([MþNa]þ , C13H24NaOþ2 ; calc. 235.1674).
Data of 31. White solid. M.p. 100–1028. [a]2D0 ¼ þ15 (c¼1, CHCl3). IR (CHCl3): 3401, 2924, 1732,
1
1466, 1366, 1244, 1046. H-NMR (300 MHz, CDCl3): 3.86 (ddd, J¼3.3, 9.4, 11.0, 1 H); 3.76 (d, J¼7.4,

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CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
1 H); 3.60–3.75 (m, 1 H); 3.39 (d, J¼7.4, 1 H); 1.18 (s, 3 H); 0.98 (s, 3 H); 0.92 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 24.0 (CH2); 24.8 (Me); 26.8 (Me); 30.5 (CH2); 30.8 (C); 31.5 (CH2); 33.4 (Me); 34.5
(CH2); 35.3 (CH2); 35.7 (CH2); 41.5 (C); 44.5 (CH); 59.1 (CH2); 74.4 (C); 77.8 (CH2); 86.7 (C). HR-MS:
291.1938 ([MþNa]þ , C16H28NaOþ3 ; calc. 291.1936).
Ozonolysis of (E)-Triene 21. Compound 21 (140 mg, 0.31 mmol) was dissolved in AcOEt (10 ml),
and an O3 flow of 0.1 l/min (10% O2/90% O3) was passed through the soln. for 2 min at ꢀ788. After that,
Me2S (0.5 ml) was added, and the mixture stirred for 12 h, evaporated to dryness, and purified on SiO2 to
give the previously described products 12 (10 mg, 28%) and 13 (18 mg, 41%).
(4aS,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-2,5,5,8a-tetramethylnaphthalene-1-carbaldehyde (32). Com-
pound 21 (102 mg, 0.2 mmol) was dissolved in acetone (10 ml), and a soln. of ca. 5 mg of RuCl3 ·
3 H2O and NaIO4 (171 mg, 0.87 mg) in H2O (2 ml) was added. The mixture was stirred at r.t. for 30 min,
diluted with CH2Cl2, and the org. layer was washed with H2O and dried (Na2SO4). The soln. was
evaporated at reduced pressure, and the residue was purified with SiO2 CC to give 32 (14 mg, 32%) and
methyl (4aS,8aS)-8-formyl-1,3,4,5,6,8a-hexahydro-2,2,7-trimethylnaphthalene-4a(2H)-carboxylate (33;
22 mg, 42%) [18].
Data of 32. Colorless oil. [a]2D0 ¼ ꢀ17 (c¼0.4, CHCl3). IR (CHCl3): 2925, 1716, 1673. 1H-NMR
(300 MHz, CDCl3): 9.97 (s, 1 H); 1.96 (s, 3 H); 1.11 (s, 3 H); 0.84 (s, 3 H); 0.79 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 18.4 (CH2); 19.0 (CH2); 19.3 (Me); 20.3 (Me); 21.8 (Me); 33.4 (C); 33.5 (Me); 36.3
(CH2); 36.7 (C, CH2); 41.7 (CH2); 51.7 (CH); 143.8 (C); 153.7 (C); 192.8 (CH). HR-MS: 243.1819 ([Mþ
Na]þ , C15H24NaOþ ; calc. 243.1725).
4-[(1S)-2,2-Dimethyl-6-methylidenecyclohexyl]butan-2-one (34). Compound 12 (80 mg, 0.33 mmol)
was dissolved in benzene/pyridine 1:3 (3 ml), and Pb(OAc)4 (219 mg, 5 equiv.) and Cu(OAc)2 (2 mg)
was added. The mixture was stirred under reflux for 2 h. Then, ethylene glycol was added, and the
mixture was diluted with CH2Cl2. The org. layer was washed with H2O, dried (Na2SO4), evaporated, and
purified over SiO2, yielding a mixture of isomers 34, 4-[(1S)-2,6,6-trimethylcyclohex-2-en-1-yl]butan-2-
one (35), and 4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one (36) [32] (22 mg, 66% for all three
compounds together), as well as (1S,2S)-1,3,3-trimethyl-2-(3-oxobutyl)cyclohexyl acetate (37; 9 mg,
14%).
1
Data of 37. Colorless oil. [a]2D0 ¼ þ14 (c¼1, CHCl3). IR (CHCl3): 2952, 1724, 1366, 1247. H-NMR
(300 MHz, CDCl3): 2.17 (s, 3 H); 1.97 (s, 3 H); 1.52 (s, 3 H); 0.98 (s, 3 H); 0.88 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 19.8 (CH2); 20.4 (Me); 20.6 (CH2); 22.4 (Me); 23.1 (Me); 29.9 (Me); 32.6 (Me); 35.7
(C); 37.6 (CH2); 40.5 (CH2); 46.3 (CH2); 53.0 (CH); 87.7 (C); 170.1 (C); 209.2 (C). HR-MS: 277.1776
([MþNa]þ , C15H26NaOþ3 ; calc. 277.1780).
4-[(1S,6S)-2,2,6-Trimethyl-6-(pyridin-2-ylsulfanyl)cyclohexyl]butan-2-one (38). Compound 12
(80 mg, 0.33 mmol) was dissolved in CH2Cl2 (10 ml), and (COCl)2 (1.1 ml) was added. The mixture
was stirred at r.t. for 12 h and evaporated. After that, pyridine-2-thiol N-oxide (50 mg) and DMAP
(4 mg) dissolved in benzene (10 ml) containing pyridine (0.06 ml) were added. The mixture was
maintained under reflux during 2 h, concentrated, and purified with SiO2 CC to yield 34 (8 mg, 12%) and
38 (24 mg, 24%).
Data of 38. Colorless oil. [a]2D0 ¼ þ49 (c¼1, CHCl3). IR (CHCl3): 2949, 1727, 1668. 1H-NMR
(300 MHz, CDCl3): 8.49 (d, J¼4.8, 1 H); 7.49 (dd, J¼6.8, 1 H); 7.20–7.30 (m, 1 H); 7.07 (dd, J¼6.0,
1 H); 2.07 (s, 3 H); 1.38 (s, 3 H); 0.96 (s, 3 H); 0.88 (s, 3 H). 13C-NMR (300 MHz, CDCl3): 16.8 (Me); 21.4
(Me); 21.4 (CH2); 21.7 (Me); 24.8 (CH2); 28.3 (Me); 29.7 (CH2); 37.6 (CH2); 40.9 (C); 46.8 (CH2); 50.7
(CH); 57.3 (C); 121.5 (CH); 127.5 (CH); 136.1 (CH); 149.6 (CH); 170.9 (C); 209.3 (C). HR-MS:
328.1796 ([MþNa]þ , C18H27NNaOSþ ; calc. 328.1711).
In addition, compound 38 (24 mg, 0.08 mmol) was oxidized with m-chloroperbenzoic acid
(MCPBA) in CH2Cl2 at ꢀ808 for 3 h. Then, the mixture was treated with sat. aq. soln. of FeSO4 and
diluted with CH2Cl2. The org. layer was neutralized with sat. aq. soln. of NaHCO3, dried (Na2SO4), and
evaporated to dryness. The resulting unstable residue was maintained in dioxane at 808 for 2 h, and the
soln. was evaporated in vacuum. Purification with SiO2 CC gave compound 34 (12 mg, 80%).
[(4aS,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]methanol (39). Com-
pound 32 (50 mg, 0.23 mmol) was dissolved in i-PrOH (4 ml), NaBH4 (8 mg) was added, and the
mixture was stirred at r.t. for 2 h. The excess of reagent was destroyed with sat. aq. soln. of NaHSO4, and

CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
437
the mixture was extracted with CH2Cl2. The org. extract was dried (Na2SO4), filtered, and concentrated
under reduced pressure. The solid residue was purified with SiO2 CC to give 39 (48 mg, 94%). Colorless
oil. [a]2D0 ¼ þ77 (c¼1, CHCl3). IR (CHCl3): 3317, 2922, 2863, 1457, 1374. 1H-NMR (300 MHz, CDCl3):
4.18 (d, J¼11.5, 1 H); 4.03 (d, J¼11.5, 1 H); 1.71 (s, 3 H); 0.95 (s, 3 H); 0.88 (s, 3 H); 0.83 (s, 3 H).
13C-NMR (75 MHz, CDCl3): 18.9 (CH2); 19.0 (Me); 19.3 (C); 20.7 (Me); 21.6 (Me); 29.7 (CH2); 33.3
(Me); 33.7 (CH2); 36.9 (CH2); 38.2 (C); 41.7 (CH2); 51.8 (CH); 58.4 (CH2); 132.5 (C); 141.1 (C). HR-
MS: 245.1979 ([MþNa]þ , C15H26NaOþ ; calc. 245.1881).
(4aS,8aS)-1,2,3,4,4a,5,8,8a-Octahydro-1,1,4a,6-tetramethyl-5-methylidenenaphthalene (40). Com-
pound 39 (73 mg, 0.32 mmol) was dissolved in pyridine (3 ml), TsCl (85 mg) was added, and the
mixture was stirred at r.t. for 1 h. After this time, the mixture was washed with a 2% aq. soln. of HCl and
extracted with CH2Cl2. The org. extract was neutralized with sat. aq. soln. of NaHCO3, dried (Na2SO4),
filtered, and evaporated to dryness. SiO2 CC yielded 40 (13 mg, 72%) [15].
[(4aS,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]methyl Trifluoroacetate
(41). Compound 39 (30 mg, 0.13 mmol) was dissolved in CH2Cl2/pyridine 3 :1 (10 ml), (CF3CO)2O
(220 ml, 0.16 mmol) was added, and the mixture was stirred at ꢀ208 for 3 h. After this time, the mixture
was washed with a 2% aq. soln. of HCl and extracted three times with CH2Cl2. The org. layer was
neutralized with sat. aq. soln. of NaHCO3, dried (Na2SO4), and filtered. The soln. was evaporated, and
the residue purified with SiO2 CC to yield 41 (42 mg, 99%). Colorless oil. 1H-NMR (300 MHz, CDCl3):
4.90 (dd, J¼12.0, 15.1, 2 H); 1.71 (s, 3 H); 1.01 (s, 3 H); 0.93 (s, 3 H); 0.88 (s, 3 H). 13C-NMR (CDCl3):
18.8 (CH2); 18.9 (Me); 19.6 (Me); 20.8 (Me); 21.6 (Me); 29.8 (C); 33.2 (Me); 33.9 (CH2); 36.5 (CH2);
37.9 (C); 41.6 (CH2); 51.3 (CH); 64.4 (CH2); 132.9 (C); 138.1 (C). FAB-MS (pos.): 349.1646 ([MꢀCF3]þ ),
363.2343 ([MꢀCF3 þNa]þ ).
Treatment of 41 with KCN. KCN (14 mg, 0.21 mmol) was added to a soln. of compound 41 (25 mg,
0.07 mmol) in MeCN (10 ml), and the mixture was stirred for 3 h at 1308. Then, the mixture was washed
with H2O and extracted three times with CH2Cl2. The org. extract was dried (Na2SO4), filtered, and the
soln. was concentrated in vacuum. Purification with SiO2 CC gave 40 (10 mg, 69%).
[(4aS,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]acetonitrile (42). A soln.
of BF3 ·Et2O (0.02 ml, 3 equiv.) and cyano(trimethyl)silane (0.03 ml, 4 equiv.) in CH2Cl2 (0.22 ml) was
added to a soln. of 41 (11 mg, 0.05 mmol) in CH2Cl2 (0.5 ml) at ꢀ108, and the mixture was stirred for 1 h.
Then, a sat. aq. soln. of NaHCO3 was added, and the mixture was stirred for further 45 min at r.t. The
mixture was extracted with CH2Cl2, and the org. layer was washed with a 1n aq. soln. of HCl, neutralized
with sat. aq. soln. of NaHCO3, dried (Na2SO4), filtered, and the soln. was concentrated in vacuum. The
residue was purified with SiO2 CC to yield 40 (3 mg, 23%) and 42 (7 mg, 58%). Colorless oil each.
1H-NMR (300 MHz, CDCl3): 3.14 (d, J¼12.0, 2 H); 1.61 (s, 3 H); 1.01 (s, 3 H); 0.99 (s, 3 H); 0.86 (s, 3 H).
13C-NMR (75 MHz, CDCl3): 18.8 (CH2); 18.9 (CH2); 19.1 (Me); 21.9 (Me); 22.9 (Me); 23.4 (CH2); 31.6
(CH2); 32.1 (C); 32.9 (Me); 35.3 (C); 36.3 (CH2); 41.3 (CH2); 49.0 (CH); 118.2 (CN); 124.6 (C); 142.5
(C). HR-MS: 254.1882 ([MþNa]þ , C16H25NNaþ ; calc. 254.1885).
2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-Octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethanol (43). To a soln.
of 42 (40 mg, 0.17 mmol) in toluene (10 ml), a 1m soln. of DIBALH in toluene (0.34 ml, 0.34 mmol) was
added, and the mixture was stirred at ꢀ788 for 1.5 h. After this time, the mixture was diluted with a 2n aq.
soln. of HCl, and then extracted with CH2Cl2. The solvent was evaporated at reduced pressure, the
residue was redissolved in i-PrOH (4 ml), and NaBH4 (6 mg) was added, and the mixture was stirred at
r.t. for 2 h. A sat. aq. soln. of NaHSO4 was added, and the mixture was extracted with CH2Cl2. The org.
layer was dried (Na2SO4), filtered, and the soln. was concentrated under reduced pressure. The solid
residue was purified with SiO2 CC to afford 43 (31 mg, 78%) [22].
Methyl (4aS,8aS)-1,3,4,5,6,8a-Hexahydro-8-(hydroxymethyl)-2,2,7-trimethylnaphthalene-4a(2H)-
carboxylate (44). Compound 33 (50 mg, 0.19 mmol) was dissolved in i-PrOH, NaBH4 (7 mg) was
added, and the mixture was stirred at r.t. for 3 h. The excess of reagent was destroyed with sat. aq. soln. of
NaHSO4, and the mixture was extracted with CH2Cl2. The org. layer was dried (Na2SO4), filtered, and
the soln. was concentrated under reduced pressure. The solid residue was purified with SiO2 CC to give 44
(49 mg, 98%) [18].
Methyl (4aS,8aS)-8-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-1,3,4,5,6,8a-hexahydro-2,2,7-trimethyl-
naphthalene-4a(2H)-carboxylate (45). Compound 44 (20 mg, 0.075 mmol) was dissolved in pyridine

438
CHEMISTRY & BIODIVERSITY – Vol. 7 (2010)
(5 ml), and TBDMSCl (22 mg, 0.15 mmol) was added. The mixture was stirred at r.t. for 12 h. After this
time, it was washed with a 1m aq. soln. of HCl and extracted with CH2Cl2. The org. extract was neutralized
with sat. aq. soln. of NaHCO3, dried (Na2SO4), filtered, and the soln. was concentrated under reduced
pressure. Purification with SiO2 CC yielded 45 (25 mg, 89%). Colorless oil. [a]2D0 ¼ þ16 (c¼1, CHCl3).
IR (CHCl3): 2951, 2857, 1730, 830. 1H-NMR (300 MHz, CDCl3): 4.30 (d, J¼11.0, 1 H); 3.97 (d, J¼11.0,
1 H); 3.60 (s, 3 H); 2.74 (dd, J¼4.6, 12.8, 1 H); 1.68 (s, 3 H); 0.89 (s, 3 H); 0.84 (s, 3 H); 0.03 (s, 3 H); 0.02
(s, 3 H). 13C-NMR (75 MHz, CDCl3): ꢀ5.4 (2 Me); 18.4 (C); 19.7 (Me); 22.7 (CH2); 24.1 (Me); 26.0 (3
Me); 29.8 (CH2); 30.1 (C); 31.4 (CH2); 32.0 (Me); 32.9 (CH); 34.0 (CH2); 36.4 (CH2); 44.9 (C); 51.8
(Me); 66.9 (CH2); 126.8 (C); 132.2 (C); 178.4 (C). HR-MS: 403.2597 ([MþNa]þ , C22H40NaO3Siþ
;
403.2644).
[(4aS,8aR)-3,5,6,7,8,8a-Hexahydro-2,7,7-trimethylnaphthalene-1,4a(4H)-diyl]dimethanol (46). Com-
pound 45 (25 mg, 0.06 mmol) was dissolved in THF, 2 ml of a 1m soln. of LiAlH4 in THF were added, and
the mixture was stirred at reflux for 1 h. After that, the mixture was diluted with CH2Cl2, the org. layer
was washed with H2O, dried (Na2SO4), and the soln. was evaporated to dryness. Purification over SiO2
gave 46 (12 mg, 78%) [18].
Methyl (4aS,8aS)-1,3,4,5,6,8a-Hexahydro-2,2,7-trimethyl-8-[(tetrahydro-2H-pyran-2-yloxy)methyl]-
naphthalene-4a(2H)-carboxylate (49). A soln. of 44 (80 mg, 0.3 mmol), 3,4-dihydro-2H-pyran (DHP;
0.14 ml, 1.5 mmol), and a cat. amount of TsOH in CH2Cl2 (8 ml) was stirred at r.t. for 1.5 h. Then, the
mixture was successively washed with sat. aq. soln. of NaHCO3, H2O, and brine. The org. layer was dried
(Na2SO4), filtered, and the solvent was evaporated under reduced pressure to give a yellow oil, which was
purified with SiO2 CC, to give the mixture of diastereoisomers 47.
Data of Methyl 1,3,4,5,6,8a-Hexahydro-2,2,7-trimethyl-8-[(tetrahydro-2H-pyran-2-yloxy)methyl]-
naphthalene-4a(2H)-carboxylate (47): HR-MS: 373.2201 ([MþNa]þ , C21H34NaO4þ ; calc. 373.2355).
The mixture of diastereoisomers 47 (76 mg, 0.24 mmol) was reduced with a 1m soln. of LiAlH4
(0.3 ml) in THF at r.t. for 3 h to yield a mixture of diastereoisomers 48.
Data of {1,3,4,5,6,8a-Hexahydro-2,2,7-trimethyl-8-[(tetrahydro-2H-pyran-2-yloxy)methyl]naphtha-
len-4a(2H)-yl}methanol (48): HR-MS: 345.2508 ([MþNa]þ , C20H34NaO3þ ; calc. 345.2406).
Finally, the mixture of diastereoisomers 48 (40 mg, 0.12 mmol) was dissolved in dried THF (20 ml),
and NaH (31 mg, 1.24 mmol) was added. The mixture was stirred under reflux for 3 h. After this time, CS2
(228 ml) was added, after 30 min, MeI (118 ml) was added, and the mixture was stirred under reflux for
1 h. After that, the mixture was diluted with CH2Cl2, the org. layer was washed with H2O, dried
(Na2SO4), filtered, and the soln. was evaporated to dryness. Purification over SiO2 gave the
diastereoisomeric mixture 49.
Data of Tetrahydro-2-{[3,4,4a,5,6,7,8,8a-Octahydro-2,7,7-trimethyl-4a-{[(2-methyl-1l6,2l4-disulfyn-1-
ylidyne)methoxy]methyl}naphthalen-1-yl]methoxy}-2 H-pyran (49): HR-MS: 435.2755 ([MþNa]þ
,
C22H36NaO3Sþ2 ; calc. 435.2004). These three transformations were also followed by the 1H-NMR spectra
of diastereoisomeric mixtures of 47, 48, and 49.
[(4aR,8aR)-3,4,4a,5,6,7,8,8a-Octahydro-2,4a,7,7-tetramethylnaphthalen-1-yl]methanol (50). Xan-
thate 49 (50 mg, 0.12 mmol) was dissolved in dioxane (5 ml), and Et3N (0.03 ml, 0.3 mmol), H3PO2
(0.1 ml, 0.9 mmol), and a soln. of AIBN (15 mg) in dioxane (3 ml) were added, and the mixture was
stirred under reflux for 3 h. Then, it was diluted with CH2Cl2, the org. layer was washed with H2O, dried
(Na2SO4), and the soln. was evaporated to dryness. Purification with SiO2 CC yielded 50 (39 mg, 58%
from 44), which had physical and spectroscopic data identical to those given in [40].
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Received February 1, 2009