Quirogane, prenopsane, and patzcuarane skeletons obtained by photochemically induced molecular rearrangements of longipinene derivatives

Article abstract of DOI:10.1021/np020158s

Ultraviolet irradiation of (1R,3S,4S,5S,10R,11R)-1-acetyloxy-7-oxolongipin-8-ene (6), prepared from longipinene diesters isolated from Stevia salicifolia, afforded the new quirogane (7) and prenopsane (8) derivatives, as the major products, together with the minor secondary photoproduct (1R,3R,5R,8S,11S)-1-acetyloxy-7-oxopatzcuar-9-ene (9), which possesses a novel tricyclic sesquiterpene skeleton. The stereostructures of the new compounds 7-9 were mainly determined by NMR techniques including COSY, HSQC, HMBC, and NOESY in combination with molecular modeling obtained by density functional theory calculations. A reaction mechanism accounting for the observed transformations is proposed.

Full text of DOI:10.1021/np020158s

1398
J . Nat. Prod. 2002, 65, 1398-1411
Qu ir oga n e, P r en op sa n e, a n d P a tzcu a r a n e Sk eleton s Obta in ed by
P h otoch em ica lly In d u ced Molecu la r Rea r r a n gem en ts of Lon gip in en e
Der iva tives
Myriam Mele´ndez-Rodr´ıguez, Carlos M. Cerda-Garc´ıa-Rojas, and Pedro J oseph-Nathan*
Departamento de Quı´mica, Centro de Investigacio´n y de Estudios Avanzados del Instituto Polite´cnico Nacional,
Apartado 14-740, Me´xico, D. F., 07000 Mexico
Received April 10, 2002
Ultraviolet irradiation of (1R,3S,4S,5S,10R,11R)-1-acetyloxy-7-oxolongipin-8-ene (6), prepared from
longipinene diesters isolated from Stevia salicifolia, afforded the new quirogane (7) and prenopsane (8)
derivatives, as the major products, together with the minor secondary photoproduct (1R,3R,5R,8S,11S)-
1-acetyloxy-7-oxopatzcuar-9-ene (9), which possesses a novel tricyclic sesquiterpene skeleton. The
stereostructures of the new compounds 7-9 were mainly determined by NMR techniques including COSY,
HSQC, HMBC, and NOESY in combination with molecular modeling obtained by density functional theory
calculations. A reaction mechanism accounting for the observed transformations is proposed.
Molecular rearrangements of carbocyclic structures are
important tools for the synthetic organic chemists because
they allow obtaining, in a single step, new carbocyclic
skeletons whose preparation through alternate synthetic
methods would involve a more complicated pathway. In
particular, photochemical rearrangements have contrib-
uted to the development of efficient and selective trans-
formations employed in the preparation of complex bioac-
tive molecules.1-3 In this sense, natural products, due to
their structural versatility and stereochemical variations,4,5
represent excellent models for experimental and theoretical
chemists to conduct these kind of studies.
Several highly functionalized longipinene derivatives are
found as the main constituents of many species of the genus
Stevia.6 These classes of substances, whose absolute con-
figuration is known,7 have shown an important tendency
to undergo molecular rearrangements due to the strained
fused cyclobutane located between a six- and a seven-
membered ring.8-15 These naturally occurring sesquiter-
penoids are generally functionalized at C-1 with a carbonyl
group and at C-7, C-8, C-9, and C-13 with hydroxyl and/or
acyloxy groups.6
In previous investigations,14,15 we have shown that,
under ultraviolet irradiation, the longipinene derivative 1
underwent photochemical transformations into 2-5 (Scheme
1) owing to the presence of an R,â-unsaturated cyclohex-
enone moiety with a cyclobutane ring attached to the
â-position. To further explore new photochemical rear-
rangements of longipinene derivatives to obtain unusual
and highly functionalized tricyclic sesquiterpenes, we
decided to prepare a new longipinene derivative having the
R,â-unsaturated carbonyl group at the seven-membered
ring instead of at the six-membered ring. This new
substrate would have a carbonyl group at C-7 and R,â-
unsaturation between C-8 and C-9 and also would possess
a four-membered ring attached to the â-position.
(1S,3S,4S,5S,8S,11R)-1-acetyloxy-7-oxoquirog-9-ene (7),
(1R,3S,4R,5S,10R,11R)-1-acetyloxy-7-oxoprenops-8-ene (8),
and (1R,3S,5R,8S,11S)-1-acetyloxy-7-oxopatzcuar-9-ene (9).
It is pertinent to mention that the latter substance is based
on a new carbocyclic skeleton.
During our efforts toward the preparation of starting
material 6 for the photochemical studies, new aspects of
the chemistry of naturally occurring highly oxygenated
longipinene derivatives were found. Furthermore, the
results obtained in this work provided new knowledge
about the photochemistry of strained sesquiterpenes, which
can be useful in the design of synthetic strategies, including
those for obtaining new carbocyclic ring systems.
Resu lts a n d Discu ssion
Compound 6 was prepared from the longipinantriol 10,
which was easily obtained from the natural longipinendi-
olone diesters present in the roots of S. salicifolia.16 To
achieve such a transformation, it was necessary to protect
the secondary hydroxyl groups at C-1 and C-9 in 10, to
oxidize the remaining hydroxyl group at C-7, and, finally,
to eliminate the protected hydroxyl group at C-9. Thus, in
a first approach, we proceeded to acetylate 10 with Ac2O
(2.15 equiv) in pyridine at -20 °C for 21 days. Chromato-
graphic separation of the crude material afforded the
triacetylated derivative 1116 in 17% yield, the mixture of
diacetylated compounds 12-14 (55%), and the monoacety-
lated products 15, 16, and 17 (15%, 7%, and 2%, respec-
tively). Starting material 10 was also recovered (4%). The
position of each hydroxyl and/or acetate group in 11-17
1
was evident after comparison of the H NMR data of these
compounds with those reported for 10,16 11,16 and 12.13 The
1H and 13C NMR data of 13-17 and other molecules
obtained during the preparation of 6 are summarized in
Tables 1-4 and in the Experimental Section. FLOCK17 or
HMBC correlations were very useful to assign the quater-
nary carbons C-6 and C-10, since C-6 showed correlations
with the proton signals for the gem-dimethyl group
(Me-12 and Me-13), while C-10 showed a correlation with
the proton signal for Me-14. The individual 1H and 13C
NMR assignment of Me-12 and Me-13 was established by
NOESY correlations from Me-12 to H-4 and from Me-13
to H-11, together with a HETCOR spectrum. In those cases
where the NOESY experiments did not allow such proton
In this paper we describe the preparation of (1R,3S,4S,
5S,10R,11R)-1-acetyloxy-7-oxolongipin-8-ene (6) from the
natural longipinene diesters of Stevia salicifolia Cav.
(Asteraceae), as well as the exploration of its photochemical
reactivity. Ultraviolet irradiation of 6 (Scheme 2) afforded
* To whom correspondence should be addressed. Tel: (52-55) 5747-7112.
Fax: (52-55) 5747-7137. E-mail: pjoseph@nathan.chem.cinvestav.mx.
10.1021/np020158s CCC: $22.00
© 2002 American Chemical Society and American Society of Pharmacognosy
Published on Web 08/23/2002

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1399
Sch em e 1. (4R,5S,7S,8R,9S,10R,11R)-7,8,9-Triacetyloxy-1-oxolongipin-2-ene (1) and Its Photoproducts 2-5
Sch em e 2. (1R,3S,4S,5S,10R,11R)-1-Acetyloxy-7-oxolongipin-8-ene (6) and Its Photoproducts 7-9
assignments, due to their chemical shift proximity, they
were followed by inspection of the HETCOR data taking
into account the 13C assignments determined by analogy
with the whole series of new and previously reported deriv-
atives.7-13,16
F igu r e 1. Lowest energy conformation of 10.
mum energy conformation of triol 10 (Figure 1) obtained
by molecular mechanics calculations (MMX)18 and subse-
quent geometry optimization using density functional
theory computations19 at the pBP/DN** level of theory. The
increased reactivity of the remaining secondary hydroxyl
group at C-1 with respect to that at C-7 can be explained
by its pseudo-equatorial orientation in the half-chair six-
membered ring conformation present in 10 (Figure 1)
together with the lack of quaternary carbon atoms at the
R-positions, which provided an important steric effect, as
is the case of the hydroxyl group at C-7.
The product ratio for the monoesterified derivatives 15,
16, and 17 was 7.5:3.5:1.0, reflecting an important differ-
ence in the chemical reactivity of the three secondary
hydroxyl groups in compound 10. The chemical reactivity
difference between the hydroxyl groups at C-7 and C-9 was
as expected, in agreement with their different orientation,
7-pseudo-equatorial and 9-pseudo-axial, in the twist-chair
seven-membered ring conformation previously described for
the longipinene system7 and clearly observed in the mini-
The 1H NMR spectrum of the mixture of diacetates
12-14 indicated that the major product was the 1,7-
diacetate 14 (ca. 80%). The mixture was oxidized with

1400 J ournal of Natural Products, 2002, Vol. 65, No. 10
Mele´ndez-Rodrı´guez et al.
CrO3/AcOH at room temperature for 2 h, affording a
mixture of the isomeric ketones 18, 19, and 20 in 68% yield,
1
in a 3.6:1.0:15.4 ratio, respectively, as shown by H NMR.
Surprisingly, under these oxidizing conditions, the intro-
duction of a hydroxyl group at C-3 in the longipinane
system occurred, further affording compound 21 in 8%
yield. Its molecular formula C19H28O6 (HREIMS, m/z
352.1876) was consistent with the presence of an additional
hydroxyl group in 21 in comparison to the HREIMS data
of 18-20. The introduction of the hydroxyl group at C-3
was also established by the IR broad absorption at 3471
1
cm-1 (OH, br) and the H NMR signals at δH 2.53 (1H, dd,
J 2R,2â ) 16.6, J 1,2R ) 10.0 Hz), 1.94 (1H, dd, J 2R,2â ) 16.6,
J 1,2â ) 5.0 Hz), and 5.25 (1H, ddd, J 1,2R ) 10.0, J 1,2â ) 5.0,
J 1,11 ) 2.9 Hz) for the methylene protons H-2R and H-2â
and the methine proton H-1, respectively. Furthermore, the
singlet at δH 1.46 for Me-15, in combination with the
FLOCK17 correlation between Me-15 and the quaternary
carbon C-3 at δC 74.3, was in agreement with the hydroxyl
group at C-3. The R configuration at C-3 was evident from
the NOESY correlation between Me-14 and Me-15, indicat-
ing that both methyl groups are located on the â-face of
the molecule and that the hydroxyl group at C-3 possesses
an R-orientation. The presence of a keto group at C-9 was
confirmed by the FLOCK17 correlation between the carbo-
nyl carbon (δC 211.6, C-9) and the signal for Me-14 (δH
1.26). The individual assignment of the signals for the
methylene protons H-8R (3.14, 1H, dd, J ) 13.0, 1.5 Hz)
and H-8â (2.82, 1H, dd, J ) 13.0, 7.2 Hz) was achieved
from NOESY correlations, since the signal at δH 3.14
(H-8R) correlated with H-11 and Me-13. Crystallization of
21 from CHCl3/hexane yielded suitable crystals for an
X-ray study. As shown in Figure 2, the X-ray structure
confirmed the R-orientation of the hydroxyl group at C-3
in 21.
Hydrolysis of the acetate groups in the mixture of
ketones 18-20 with KOH in MeOH/H2O under reflux for
2 h afforded, after chromatographic separations, the un-
saturated compound 22 (60%), ketodiol 2316 (9%), and the
epimeric mixture of ketodiols 24 and 25 (9% and 5%,
respectively). The 1H NMR spectrum of 22 (Table 2) showed
two vinylic protons at δH 6.05 (H-7) and 5.84 (H-8), which
correlated, in the HETCOR diagram, with the sp2 carbon
signals at δC 150.3 (C-7) and 126.1 (C-8), respectively, in
agreement with the presence of the R,â-unsaturated ketone.
The signal at δH 4.36 (1H, ddd, J ) 9.7, 5.3, 3.0 Hz, H-1)
was consistent with the presence of a hydroxyl group at
C-1. In addition, the IR bands at 3608, 3480 (OH), and 1650

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1401

1402 J ournal of Natural Products, 2002, Vol. 65, No. 10
Mele´ndez-Rodrı´guez et al.
Ta ble 4. 13C NMR Data of Compounds 6, 13-17, 19-22, 24, 25, and 27-41a
compd
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-11
C-12
C-13
C-14
C-15
6
76.2
75.9
75.9
76.2
74.0
78.4
75.3
75.5
74.3
74.5
74.6
74.5
74.8
75.8
44.2
77.3
74.2
77.6
77.4
77.7
74.0
74.4
75.7
74.4
75.8
74.1
75.7
32.9
33.1
33.3
33.3
35.8
36.3
32.8
32.4
41.0
35.9
35.9
35.6
35.8
32.9
26.8
32.9
36.2
32.9
33.2
33.2
35.8b
36.4
33.1
36.0
33.3
41.6
33.1
37.5
37.3
37.5
37.5
37.8
37.4
37.4
37.4
74.3
37.6
37.6
37.6
37.6
37.6
38.6
37.4
37.4
37.4
37.6
37.5
37.8
37.4
37.3
37.4
37.6
74.6
37.4
50.7
45.0
45.4
45.3
45.6
45.3
45.7
46.6
52.3
44.8
46.8
45.9
51.0
44.6
49.7
45.3
45.6
45.1
45.4
45.3
45.7
45.4
45.3
45.5
45.5
52.1
45.3
54.0
56.5
56.8
56.9
57.0
56.9
54.4
56.0
50.0
55.2
56.5
56.5
54.3
54.9
62.3
56.2
56.7
56.3
56.6
56.7
57.0
56.9
56.5
56.8
56.8
48.2
56.3
46.4
36.5
35.6
36.5
35.7
36.5
46.6
36.6
36.6
39.1
37.3
37.3
46.4
39.2
37.0
36.1
35.9
36.6
35.9
36.5
36.2
36.5
36.0
36.1
36.1
46.4
35.6
205.5
70.8
73.1
69.9
73.7
70.9
210.5
75.1
75.4
150.3
73.9
73.8
205.9
150.2
73.8
74.9
75.2
70.8
75.2
69.9
75.9
71.0
75.3
75.5
75.3
210.7
73.0
127.7
35.9
35.8
38.9
35.8
35.9
41.7
43.0
43.0
126.1
47.2
47.5
127.4
126.1
36.9
32.5
32.6
35.8
36.2
39.0
35.9b
36.0
32.1
32.2
35.8
41.6
32.6
159.6
78.0
75.5
75.9
75.8
74.5
77.1
212.1
211.6
206.3
214.3
214.6
160.6
205.8
75.8
79.3
79.7
80.1
75.2
75.7
75.7
80.6
77.5
77.9
75.5
76.6
79.5
41.7
43.1
44.2
44.0
44.3
43.3
43.4
53.3
53.2
52.4
53.6
53.6
41.9
52.2
47.5
43.6
43.8
43.6
44.3
44.1
44.4
43.7
43.1
43.4
44.3
43.5
43.5
48.2
40.2
39.6
39.3
42.2
43.0
42.1
43.6
43.8
45.1
46.4
47.2
51.3
42.4
72.0
40.8
43.5
40.4
39.8
39.4
42.3
43.2
40.6
43.3
39.7
42.0
40.6
26.2b
17.5
18.6
17.5
18.8
17.5
24.3
23.6
23.7
27.4
22.0
21.5
26.3
27.4b
26.0
18.8
18.8
17.5
19.0
17.5
19.1
17.5
18.9
18.9
19.0
24.3
18.6
26.3b
26.9
26.7
27.0
26.7
26.9
22.6
25.7
25.7
27.5
26.2
26.2
26.3
27.7b
21.7
26.8
26.8
27.0
26.9
27.0
26.9
26.9
26.7
26.8
26.9
22.5
26.7
24.2
21.9
22.4
22.5
22.4
21.9
21.9
17.8
18.7
17.9
17.7
17.6
24.2
18.1
23.3
22.4
22.0
22.5
22.8
22.8
22.4
22.0
21.9
21.9
22.5
22.5
22.2
21.3
21.5
21.6
21.5
21.8
21.6
21.5
21.2
30.9
21.2
21.3
21.4
21.4
21.1
19.4
21.5
21.6
21.5
21.6
21.5
21.8
21.5
21.5
21.6
21.6
31.1
21.6
13
14
15
16
17
19
20
21
22
24
25
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
a
b
Measured in CDCl3 at 75.4 MHz; δ in ppm from TMS. Tentative assignment. The shifts due to substituents at oxygen atoms are
given in the Experimental Section.
F igu r e 2. Single-crystal X-ray structures of 21, 22, 25, and 28.
cm-1 and the UV absorption at 226 nm supported structure
22. Crystallization of 22 from ethanol afforded appropriate
crystals, which were submitted to an X-ray crystal analysis
to confirm the structure (Figure 2).

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1403
respectively. Under these reaction conditions, partial hy-
drolysis of the acetate group at C-1 in 28 was observed,
also providing the hydrolyzed R,â-unsaturated ketone 22
in 14% yield.
The 1H and 13C NMR spectra of 28 (Tables 2 and 4) were
similar to those of 22, except for the presence of an acetate
group at C-1 in 28 [H-1 (δH 5.28, 1H, ddd, J ) 9.9, 5.1, 3.1
Hz); C-1 (δC 75.8), OAc (δH 2.02, 3H, s; δC 170.6, 21.4)].
The molecular structure of 28 was confirmed by X-ray
crystallography, whose perspective view is presented in
Figure 2.
1
The IR, HREIMS, and H and 13C NMR data as well as
2D NMR correlations of compounds 24 and 25 were very
similar to each other. Detailed comparison of the NMR data
for these compounds led us to conclude that compound 25
is the C-7 epimer of 24. Their 1H NMR spectra (Table 2)
showed the H-1 and H-7 signals as methine protons
geminal to hydroxyl groups. Also, for both compounds, the
carbonyl carbon signal correlated with the Me-14, H-4,
H-11, and H-7 signals in their HMBC spectra, indicating
that the carbonyl group was located at C-9. The above data
1
The H and 13C NMR data of compound 6 (Tables 1 and
4) showed the expected resonances for the R,â-unsaturated
ketone: two vinylic protons at δH 5.83 (H-8) and 6.54
(H-9), which correlated with signals at δC 127.7 (C-8) and
159.6 (C-9) in the HETCOR diagram. The location of the
keto group at C-7 was evident from the HMBC correlation
between the carbonyl signal at δC 205.5 and the gem-
dimethyl group signal at δH 1.14 (6H, s, Me-12, Me-13).
The H-1 signal at δH 5.23 (1H, ddd, J ) 9.8, 5.5, 2.8 Hz)
and the singlet at δH 2.04 (3H, s, OAc) indicated that the
acetyl group remained at the C-1 position. In addition, the
IR [1724 (CdO acetate), 1652 cm-1 (R,â-unsaturated cy-
cloheptenone)] and UV (244 nm) data were in agreement
with structure 6.
1
and the relevant differences found in the H NMR signals
for the methylene protons H-8R and H-8â [for 24: δH 3.00
(1H, dd, J ) 12.5, 2.3 Hz, H-8R) and 2.92 (1H, dd, J ) 12.5,
8.6 Hz, H-8â); for 25: δH 2.99 (1H, dd, J ) 12.3, 9.1 Hz,
H-8R) and 2.90 (1H, dd, J ) 12.3, 2.2 Hz, H-8â)] indicated
that compounds 24 and 25 are stereoisomers, the only
difference being the relative configuration at C-7. NOESY
correlations did not provide clear information on the
stereochemistry at C-7; however crystallization of com-
pound 25 from CHCl3/hexane yielded crystals, which were
subjected to X-ray analysis. As shown in Figure 2, this
study provided unambiguous structural confirmation and
demonstrated the R-orientation for the hydroxyl group at
C-7 in 25. Consequently, the orientation of this group in
24 is â, as in naturally occurring longipinene derivatives.7
It is noteworthy that in 25 the H-4 (δH 2.25, 1H, br d, J )
5.4 Hz) and H-11 (δH 2.73, 1H, ddd, J ) 5.4, 3.0, 1.2 Hz)
signals appeared at the typical chemical shift values of
longipinenes, while surprisingly in 24 these signals ap-
peared collapsed as a broad singlet at δH 2.52. In 25, the
assignment of the C-4 (δC 45.9) and C-11 (δC 47.2) signals
was achieved from the HETCOR data. In 24, these assign-
ments were made through an HMBC experiment, where
C-4 (δC 46.8) correlated with Me-14 and Me-15, while C-11
(δC 46.4) correlated only with Me-14.
While the hydroxyl group at C-7 in 24 was easily
removed to give the R,â-unsaturated ketone 22, treatment
of 26 under the same reaction conditions unexpectedly
afforded epimer ketodiol 25 instead of 27. These findings
can be explained by a base-induced transannular 1,3-
hydride shift from C-9 to C-7 in 26 to give 25. The
R-orientation of the hydroxyl group at C-7 in ketodiol 25,
clearly observed in Figure 2, is in agreement with the
required suprafacial stereochemistry for such hydride
migration. Examples of base-induced transannular 1,4- and
1,5-hydride shifts in ketols have been frequently de-
scribed,20 while the 1,3-hydride transfer has been scarcely
observed.21
Once the preparation of 6 could be completed, it was
evident that a very limiting step was the selective genera-
tion of the diacetyloxy derivative 13 during the acetylation
of 10. To increase the yield of 13, we explored variations
of the acetylation conditions. In a first attempt, triol 10
was treated with AcCl (2.15 equiv) in acetone at room
temperature during 24 h, to afford the mixture of diacetates
12-14 (16%), monoacetate 15 (8%), and trace amounts of
a new unexpected uruapane13 derivative 29. Analysis of
1
the H and 13C NMR data of 29 (Tables 2 and 4) as well as
its 2D NMR correlations revealed that it possesses an
uruapane-type skeleton13 with secondary hydroxyl groups
at C-9 and C-11 and an acetyloxy group at C-7.
To avoid rearrangement-promoting acid conditions, we
used 4-(dimethylamino)pyridine (DMAP) as the neutral-
izing agent. Thus, when triol 10 was treated with AcCl
(2.15 equiv) and DMAP in acetone, a mixture of diacetates
12-14 was obtained in 33% yield, together with the
triacetyloxy compound 11 (24%), the monoesterified prod-
ucts 15, 16, and 17 (20%, 7%, and 2%, respectively), and
starting material 10 (12%). J ones oxidation of the mixture
12-14 and subsequent elimination of the â-acetyloxy group
in alumina yielded the desired R,â-unsaturated ketone 6
in 6% yield, together with the isomeric ketone 28 (41%),
and a mixture of the hydrolyzed products 22 and 27 (20%).
Considering the difference in reactivity among the
secondary hydroxyl groups in triol 10, a more efficient
methodology for the preparation of 6 using a protective
group was devised. Thus, triol 10 was treated with p-
nitrobenzoyl chloride (1.4 equiv) in anhydrous pyridine at
-4 °C for 24 h to give the tri-, di-, and monoesterified
products 30-36, which were separated by column chro-
matography. From this reaction, the desired C-7 monoester
35 was obtained in 10% yield. Thus, after the hydroxyl
group at C-7 was protected as a p-nitrobenzoate, acetyla-
tion of the remaining hydroxyl groups at C-1 and C-9 was
carried out with AcCl under reflux for 10 min, affording
triester 37 in very good yields (95%). Subsequent selective
hydrolysis of the p-nitrobenzoate group was achieved with
potassium hydroxide (1.6 N) at room temperature for 7 min
to yield diacetate 13 in 63% yield. Minor amounts of
diesters 38 (2%) and 39 (1%), monoesters 15 (3%) and 17
Treatment of the mixture of ketones 18-20 with alumina/
H2O (1.5:1.0 w/w) at 90 °C during 72 h afforded the isomeric
R,â-unsaturated ketones 6 and 28 in 0.5% and 64% yields,

1404 J ournal of Natural Products, 2002, Vol. 65, No. 10
Mele´ndez-Rodrı´guez et al.
1
(23%), and triol 10 (2%) were also isolated. The H and 13C
NMR data of 30-39 are listed in Tables 2-4.
(12-14 and 18-20) was achieved. Similarly, diacetate 14
and ketone 20 were selectively prepared from the p-
nitorobenzoyloxy derivative 36. Acetylation of 36 with AcCl
and subsequent selective hydrolysis in the resulting triester
41 afforded diacetate 14. J ones oxidation of 14 gave ketone
20. The selective preparation of these compounds allowed
us to determine their physical and spectroscopic data. The
preparation of diacetate 1213 and ketone 1816 was previ-
ously described.
Acetylation of the hydroxyl groups of 36 was evident
1
from the H and 13C NMR data of 41 (Tables 3 and 4). On
1
the other hand, the H and 13C NMR data of 20 (Tables 1
and 4) indicated the presence of a carbonyl group at C-9
(δC 212.1), which was confirmed by the HMBC correlations
of C-9 to H-4, Me-14, and H-7.
P h otoch em ica l Rea ctivity of 6. In view of our interest
in inducing new molecular rearrangements and after the
successful preparation of 6, we proceeded to explore its
photochemical reactivity. UV irradiation of 6 in cyclohexane
using a quartz immersion low-pressure Hg lamp for 15 min
resulted in a complex mixture of products, as judged by
the 1H NMR spectrum of the crude material. Silica gel
chromatography followed by high-performance liquid chro-
matography (HPLC) using a reversed-phase column and
MeOH/H2O (13:7) as eluent led to the purification of
compounds 7, 8, and 9 in 5%, 1%, and 3% yields, respec-
tively.
The photorearrangements of the R,â-unsaturated cyclo-
heptenone 6 can be explained considering the mechanism
outlined in Scheme 2. The photoisomerization of 6 into the
â,γ-unsaturated ketone 7 could proceed via a [1,3]-shift of
the C(4)-C(10) bond through the diradical species 6a .
Compound 8 could be a secondary photoproduct derived
from the â,γ-unsaturated ketone 7 and formed by a [1,3]-
acyl shift.22 The chiral centers at C-5 and C-11 present in
6 might induce the stereochemistry of 7 and 8. On the other
hand, formation of compound 9 appears to involve a
hydrogen migration of H-5 in species 6a to give species 6b
and subsequent C(5)-C(8) bonding on the â-side of the
molecule. The preference in the generation of this diaster-
oisomer may be due to the lack of the gem-dimethyl group
steric interaction, which could be relevant if the cyclobu-
tane ring closure occurs on the R-side of the molecule. The
proposed mechanism is consistent with those described for
analogous photorearrangements, including those of ver-
benone (42)23-26 and (4R,5S,7S,8R,9S,10R,11R)-7,8,9-tri-
acetyloxy-1-oxolongipin-2-ene (1).14,15
During the preparation of compound 6, concomitant
formation of the isomeric R,â-unsaturated ketone 28 was
achieved in a good yield. Therefore, it was interesting to
explore if the latter compound might undergo a photore-
arrangement under the same reaction conditions as those
used for 6. When a cyclohexane solution of compound 28
was irradiated using a quartz immersion low-pressure Hg
lamp, no reaction was observed and starting material was
recovered even when the irradiation was maintained for
2 h.
J ones oxidation of the hydroxyl group in 13 gave ketone
19 in 72% yield. Under these conditions, a hydroxyl group
was introduced at C-3 in 19 to give compound 40 in 12%
yield in a similar way as observed during the oxidation of
20. The 1H and 13C NMR data of 19 (Tables 1 and 4)
confirmed the presence of a carbonyl group (δC 210.5) whose
position at C-7 was deduced from the HMBC cross-peaks
between C-7/Me-12,Me-13. The individual assignment of
H-8â at δH 3.18 was deduced by NOESY correlation
between H-8â/H-4, and consequently the signal at δH 2.53
is due to H-8R. The molecular formula of 40, C19H28O6
(HREIMS, m/z 352.1888), was consistent with the presence
of an additional hydroxyl group as compared to 19. The
1H and 13C NMR spectra of 40 (Tables 3 and 4) closely
resembled those of 19, except for the signals of H-2R (δH
2.58) and H-2â (δH 1.90), which appeared as two double
doublets, and that of Me-15 (δH 1.50), which was observed
as a singlet. In the 13C NMR spectra of 40 the signal of
C-3 (δC 74.6) appeared as a quaternary carbon, which
correlated with the proton Me-15 signal in the FLOCK17
diagram. A NOESY cross-peak from Me-15 to Me-14
indicated the â-Me-15 orientation and, consequently, the
R-OH orientation and the R configuration at C-3.
Finally, removal of the acetate group at C-9 in 19 with
alumina/H2O afforded the desired R,â-unsaturated ketone
6 in 87% yield, together with the hydrolyzed analogue 27
The differences in the photochemical behavior between
the isomeric ketones 6 and 28 may be due to the differences
in the chromophores of both structures. In 6, the R,â-
unsaturated carbonyl group is conjugated to the four-
membered ring,27,28 while in 28, the cyclobutane is cross-
conjugated to the enone system.
Str u ctu r e Elu cid a tion of P h otop r od u cts 7-9 Usin g
Molecu la r Mod elin g a n d NMR Sp ectr oscop y. The
structures of 7-9 were mainly determined by analysis of
1D and 2D NMR data as well as by HREIMS. The
1
in 5% yield. The H and 13C NMR data of 27 (Tables 2 and
4) are similar to those of 6 except for the absence of the
acetyl group signals, the presence of a broad D2O-
exchangeable proton signal (δH 1.84), and the shielding of
the H-1 signal from δH 5.23 in 6 to δH 4.32 in 27. This
information indicated that 27 is the 1-hydroxy analogue
of 6.
By using this methodology, the selective preparation of
diacetate 13 and ketone 19, previously obtained in mixtures

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1405
Ta ble 5. 1H, 13C NMR and HMBC Data of Compounds 7-9a
compound 7
compound 8
compound 9
HMBC
HMBC
HMBC
position
1
δH
5.00 ddd
δC
(C to H)
δH
5.25 ddd
δC
(C to H)
δH
δC
(C to H)
75.5
2, 11
75.0
2
5.41 ddd
69.3
2
(11.8, 4.6, 3.0)
1.78 ddd
(12.3, 4.9, 4.6)
1.59 ddd
(11.9, 6.4, 6.0)
1.75 ddd
(12.3, 6.4, 3.5)
1.63 ddd
(5.4, 3.4, 2.3)
2.05 ddd
(14.8, 8.8, 5.4)
1.35 ddd
2R
â
33.3
15
32.9
15
35.5
4, 15
(12.3, 12.0, 11.8)
2.05 m
(overlap)
2.05 m
(overlap)
(12.3, 12.1, 11.9)
1.84 m
(14.8, 7.9, 2.3)
1.58 m
3
31.8
38.6
2, 15
33.8
38.3
15
15
25.7
33.8
2, 4, 15
2, 15
4R
â
2, 9, 15
2.26 m
(overlap)
2.00 dd
(13.3, 3.0)
1.67 dd
(13.3, 13.2)
5
2.02 m
48.7
11
1.94 br m
48.2
12, 13
46.0
4, 9, 12, 13
(overlap)
6
7
8
48.9
213.6
50.0
8, 12, 13
12, 13
4, 9
48.2
214.4
128.6
12, 13
12, 13, 14
61.9
215.1
74.6
4, 11, 12, 13
12, 13
4, 9
2.76 br m
5.67 ddd
3.67 br m
(9.5, 4.8, 1.2)
5.44 dd
(9.5, 1.7)
9
5.49 br d
(6.3)
121.2
14
132.2
14
5.38 ddq
(2.8, 1.5, 1.5)
123.1
14
10
11
137.9
42.1
5, 11, 14
2, 9, 14
53.8
41.2
14
14
143.8
52.1
14
2.53 br t
(2.8)
1.10 s
1.18 s
1.70 d
(1.4)
2.25 m
(overlap)
1.07 s
1.26 s
1.23 s
2.70 br m
2, 4, 9, 14
12
13
14
26.0
23.8
23.5
13
12
9
26.0
24.9
18.0
13
12
1.19 s
1.22 s
1.72 ddd
(2.2, 1.5, 0.8)
0.98 d
20.0
22.3
14.9
13
14
15
1.06 d
(6.6)
20.0
2
0.95 d
(6.9)
19.0
23.4
2
(6.3)
a
Measured in CDCl3 at 300 and 75.4 MHz, respctively; δ in ppm from TMS and J values (Hz) in parentheses. The shifts due to
substituents at oxygen atoms are given in the Experimental Section.
Ta ble 6. Calculated Dihedral Angles (deg) and Calculated and Observed Vicinal Coupling Constants (Hz) for Compounds 7-9
compound 7
compound 8
compound 9
a
b
c
a
b
c
a
b
c
Hx-C-C-Hy
φDFT
J calc
J obs
φDFT
J calc
J obs
φDFT
J calc
J obs
1,2R
1,2â
1,11
2R,3
2â,3
3,4R
3,4â
4,5
-55.3
-172.5
64.4
48.2
166.0
-47.6
4.9
11.1
2.7
5.1
11.8
4.7
4.6
11.8
3.0
4.9
12.0
d
-48.6
-165.8
47.4
57.4
175.6
-65.3
5.8
10.5
5.2
3.7
12.3
2.1
6.4
11.9
6.0
3.5
12.1
d
35.9
-77.9
-55.5
25.7
141.9
-69.9
174.0
5.3
1.8
2.4
8.6
8.3
5.4
2.3
3.4
8.8
7.9
2.0
12.2
3.0
13.2
54.6
-55.1
-61.0
26.7
3.6
3.5
2.6
8.5
1.0
d
d
d
6.3
62.3
-42.1
-54.3
3.9
2.4
5.7
3.8
10.7
0.9
d
4.8
d
4,8
5,11
8,9
9.5
54.4
3.8
0.8
2.8
rms
a
b
From density functional theory at the pBP/DN** level.19 From calculated dihedral angles.29,30 c Measured at 300 MHz in CDCl3.
d
Signal broadening or overlapping precluded the measurements.
1
correlations found in the NOESY spectra in combination
with molecular modeling, and taking into account the
absolute configuration of 6, led to the full stereochemical
assignment of the stereogenic centers present in 7-9. The
minimum energy conformations were obtained by molec-
ular mechanics calculations (MMX)18 followed by geometry
optimization using density functional theory computation19
at the pBP/DN** level of theory. The good correspondence
between the calculated29,30 and observed 1H-1H coupling
constants (Table 6) allowed us to validate the stereostruc-
tures of the new carbocyclic compounds 7-9, as well as
their conformation in solution (Figure 3).
Compound 7 had the molecular formula C17H24O3 as
deduced from HREIMS in combination with 1H and 13C
NMR data (Table 5). Interpretation of its COSY, HETCOR,
HSQC, HMBC, and NOESY spectra revealed that 7 has a
quirogane-type skeleton.12 The presence of a γ-methyl-â,γ-
unsaturated ketone moiety was evidenced by the IR band
at 1726 cm-1 and UV absorption at 298 nm. The H NMR
spectrum showed signals at δH 2.76, 5.49, and 1.70 for H-8,
H-9, and Me-14, respectively, while the 13C NMR spectrum
displayed the corresponding signals at δC 213.6, 137.9,
121.2, 50.0, and 23.5 for C-7, C-10, C-9, C-8, and C-14,
respectively. The 1H NMR spectra also displayed signals
for one proton geminal to an acetate group at δH 5.00 (H-
1), one acetate methyl group at δH 2.05, two methylene and
four methine protons, and one secondary and two tertiary
methyl groups, in agreement with the proposed structure,
which was further supported by the correlations found in
the HMBC spectrum of 7 (Table 5). In particular, the C(4)-
C(8) bond was confirmed by the COSY interactions between
H-4 and H-8 as well as the HMBC correlation between C-4
and H-9 (Table 5). The above data and NOESY interactions
between H-2â and Me-14; H-1 and H-5; H-5 and Me-12;
H-8 and Me-15; H-11 and Me-13; and Me-13 and Me-14

1406 J ournal of Natural Products, 2002, Vol. 65, No. 10
Mele´ndez-Rodrı´guez et al.
(Table 5) were in agreement with the presence of the C(4)-
C(8) and C(7)-C(10) bonds. An APT experiment was very
useful for the individual assignment of the C-5 and the
quaternary carbon C-6 signals, which had a very similar
chemical shift at δC 48.2. Individual assignments of the
methylenic protons at C-2 were confirmed by comparison
1
of the experimental H-1H coupling constant values with
those obtained from the DFT19 minimum energy confor-
mation (Table 6). NOESY interactions between H-4 and
Me-12 and between H-11 and Me-13 were consistent with
the (1R,3S,4R,5S,10R,11R)-1-acetyloxy-7-oxoprenops-8-ene
structure of 8 (Figure 3).
HREIMS and NMR data revealed that compound 9 has
the C17H24O3 molecular formula. Its IR spectrum showed
a band at 1764 cm-1, which supported the existence of a
cyclobutanone moiety. The presence of a γ-methyl-â,γ-
unsaturated ketone moiety was demonstrated by the UV
absorption at λmax 305 nm and by the 1H NMR [δH 3.67
(H-8), 5.38 (H-9), 1.72 (Me-14)] and 13C NMR signals [δC
215.1 (C-7), 74.6 (C-8), 123.1 (C-9), 143.8 (C-10), 14.9 (Me-
1
14)]. The H and 13C NMR spectra (Table 5) also showed
signals due to a methine-bearing acetyloxy group [δH 5.41
(H-1), 1.97 (OAc); δC 69.3 (C-1), 170.3, 21.3 (OAc)], two
methylenes [δH 2.05 (H-2R), 1.35 (H-2â), 2.00 (H-4R), 1.67
(H-4â); δC 35.5 (C-2), 33.8 (C-4)], one secondary methyl
group [δH 1.62-1.50 (H-3), 0.98 (Me-15); δC 25.7 (C-3), 23.4
(C-15)], and a gem-dimethyl group on a quaternary carbon
[δH 1.19 (Me-12), 1.22 (Me-13); δC 61.9 (C-6), 20.0 (C-12),
22.3 (C-13)], a methine [δH 2.70 (H-11); δC 52.1 (C-11)], and
a quaternary carbon δC 46.0 (C-5). The individual assign-
ments of the methylene protons H-2R and H-2â were
1
confirmed on the basis of calculated and observed H-1H
coupling constants (Table 6), while those of H-4R and H-4â
were determined from the NOESY spectrum. Thus, the
signal at δH 2.00 showed an interaction with the signal for
Me-12 and was assigned to H-4R (Figure 3). Consequently,
the signal at δH 1.67 corresponded to H-4â. HMBC cor-
relations between C-5 and H-4, H-9, Me-12, Me-13; between
C-6 and H-4, H-11, Me-12, Me-13; and between C-8 and
H-4 confirmed the presence of the C(5)-C(4), C(5)-C(6),
C(5)-C(8), and C(5)-C(11) bonds. The configuration at C-5
was determined by NOESY interactions between H-4R and
H-8 and between H-11 and Me-13 (Figure 3). The above
data and a literature search revealed that the structure of
9 has a novel sesquiterpenoid skeleton, which we named
patzcuarane. It is noteworthy that the carbocyclic skeleton
of 9 resembles that of R- and â-panasinsene, main compo-
nents of the essential oil of the roots of Panax ginseng.33
F igu r e 3. Lowest energy conformation using density functional theory
and relevant NOESY correlations for 7-9.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Melting points were
determined on a Fisher-J ohns apparatus and are uncorrected.
Optical rotations were determined on a Perkin-Elmer 241
polarimeter. UV spectra were obtained on a Perkin-Elmer
Lambda 12 spectrophotometer. UV spectra of compounds 30,
31, and 33 were measured in CH3CN because they were
insoluble in EtOH. IR spectra were recorded on a Perkin-Elmer
16F PC spectrophotometer. NMR measurements were recorded
on Varian Associates XL-300GS and Mercury 300 spectrom-
eters, with the NOESY, HMQC, and HMBC experiments done
on the latter instrument. Chemical shifts (δ) are given in ppm
related to tetramethylsilane. EIMS were recorded at 20 eV on
a Hewlett-Packard 5989A spectrometer. HREIMS were mea-
sured at the UCR Mass Spectrometry Facility, University of
California, Riverside, on a VG 7070 high-resolution mass
spectrometer. Column chromatography refers to flash chro-
matography34 using the indicated solvent mixture and silica
gel Merck grade 60 (230-400 mesh). Anhydrous pyridine was
(Figure 3) allowed us to establish the structure of 7 as
(1R,3S,4S,5S,8S,11R)-1-acetyloxy-7-oxoquirog-9-ene.
Compound 8 had the molecular formula C17H24O3 as
indicated by HREIMS and 1H and 13C NMR data (Table
5). The IR band at 1726 cm-1 and UV maximum absorption
at 290 nm together with the 1H and 13C NMR data
indicated the presence of an R-methyl-â,γ-unsaturated
1
ketone moiety. The H NMR spectra also showed signals
due to the same kind of protons as those observed for 7:
one proton geminal to the acetyloxy group, one acetate
methyl group, two methylene and four methine protons,
and one secondary and two tertiary methyl groups. How-
ever, analysis of 2D NMR data demonstrated that com-
pound 8 possesses the same prenopsane31 skeleton as that
of conicumol32 and prenopsanol.31 The COSY interaction
between H-4 and H-8 in combination with the HMBC cross-
peak correlations from C-7 to Me-12, Me-13, and Me-14

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1407
freshly distilled from a BaO suspension under argon. All
commercially available reagents were used as received. All of
the solvents employed were spectral or HPLC grade or were
distilled from glass prior to use. HPLC separations were
carried out employing a semipreparative Varian Dynamax C18
(5 mm) reversed-phase column (10 × 250 mm) with a precol-
umn (10 × 50 mm), using MeOH/H2O 65:35 (flow rate, 3 mL/
min) as the mobile phase on a Varian ProStar 215 solvent
delivery module and a Varian ProStar 350 refractive index
detector, both controlled by a PC with the Star WS V5
Chromatography Workstation software.
Com p u ta tion a l Meth od s. Preliminary structure refine-
ments were achieved by using MMFF94 force-field calculations
as implemented in the PC Spartan Pro molecular modeling
program (Wavefunction, Inc., Irvine, CA). Subsequent geom-
etry optimizations were carried out with the same program
using density functional theory (DFT) at the pBP/DN** level.
Acetyla tion of 10 w ith Ac2O. A solution of triol 1016 (500
mg, 2.0 mmol) in pyridine (3 mL) was treated with a solution
of Ac2O (0.4 mL, 4.2 mmol) in pyridine (1.1 mL). The reaction
mixture was stored at -20 °C for 21 days, poured over ice/
H2O, and extracted with EtOAc. The organic layer was washed
with dilute HCl, H2O, aqueous NaHCO3, and H2O, dried over
anhydrous Na2SO4, filtered, and evaporated under vacuum.
The residue was purified by column chromatography on silica
gel. Fractions that eluted with EtOAc/hexane (2:3) gave 1116
(130 mg, 17%) and the mixture of 12-14 (365.5 mg, 55%).
Fractions eluting with EtOAc/hexane (4:1) afforded 15 (90 mg,
15%), 16 (40 mg, 7%), and 17 (10 mg, 2%). Starting material
10 (20 mg, 4%) was recovered from fractions eluting with
MeOH/EtOAc (1:19).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1-Ace t yloxy-7,9-d ih y-
d r oxylon gip in a n e (15): white solid; mp 173-175 °C; [R]589
+12°, [R]578 +14°, [R]546 +15°, [R]436 +28°, [R]365 +46° (c 0.17,
CHCl3); IR (CHCl3) νmax 3614, 3466 (OH), 1720 (CdO acetate),
1258 (C-O) cm-1; 1H NMR (CDCl3, 300 MHz), see Table 1 and
δ 2.30 (2H, br s, OH), 2.03 (3H, s, OAc); 13C NMR (CDCl3, 75.4
MHz), see Table 4 and δ 170.8 (CdO acetate), 21.4 (Me-
acetate); EIMS m/z 278 [M - (H2O)]+ (0.1), 263 (0.4), 236 (5),
218 (8), 203 (12), 175 (32), 121 (43), 107 (42), 95 (100), 81 (23),
69 (30), 55 (13), 43 (43); HRDCIMS (NH3) m/z 314.2330 (calcd
for C17H28O4 + NH4+, 314.2331).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-7-Ace t yloxy-1,9-d ih y-
d r oxylon gip in a n e (16): white solid; mp 168-170 °C; [R]589
+13°, [R]578 +14°, [R]546 +17°, [R]436 +32°, [R]365 +54° (c 0.17,
CHCl3); IR (CHCl3) νmax 3604, 3448 (OH), 1726 (CdO acetate),
1260 (C-O) cm-1; 1H NMR (CDCl3, 300 MHz), see Table 1 and
δ 3.12 (2H, br s, OH), 2.08 (3H, s, OAc); 13C NMR (CDCl3, 75.4
MHz), see Table 4 and δ 171.0 (CdO acetate), 21.4 (Me-
acetate); EIMS m/z 296 [M]+ (0.1), 278 (1), 254 (2), 236 (13),
218 (19), 203 (45), 175 (51), 159 (43), 123 (61), 109 (84), 95
(94), 81 (46), 69 (71), 55 (37), 43 (100); HRDCIMS (NH3) m/z
314.2337 (calcd for C17H28O4 + NH4+, 314.2331).
(1R,3R,4S,5S,7R,10R,11R)-1,7-Dia cetyloxy-3-h yd r oxy-
9-oxolon gip in a n e (21): colorless crystals (CHCl3/hexane); mp
154-155 °C; [R]589 -17°, [R]578 -17°, [R]546 -21°, [R]436 -40°,
[R]365 -84° (c 0.18, CHCl3); IR (CHCl3) νmax 3676, 3471 (OH),
1732 (CdO acetate), 1696 (CdO cycloheptanone), 1240 (C-
1
O) cm-1; H NMR (CDCl3, 300 MHz), see Table 1 and δ 2.04
(3H, s, OAc), 2.02 (3H, s, OAc); 13C NMR (CDCl3, 75.4 MHz),
see Table 4 and δ 170.4, 169.9 (CdO acetates), 21.2, 21.0 (Me-
acetates); EIMS m/z 352 [M]+ (0.3), 292 (1), 250 (6), 232 (16),
217 (8), 189 (16), 161 (14), 135 (12), 95 (18), 69 (8), 55 (7), 43
(100); HREIMS m/z 352.1876 (calcd for C19H28O6, 352.1886).
Alk a lin e Hyd r olysis of th e Mixtu r e of 18-20. A solution
of the mixture of 18-20 (500 mg, 1.5 mmol) in MeOH (5 mL)
was treated with KOH (500 mg) dissolved in 1 mL of H2O.
The reaction mixture was refluxed for 1 h, diluted with ice/
H2O, and extracted with EtOAc. The organic layer was washed
with H2O, dried over anhydrous Na2SO4, and filtered. The
solvent was evaporated and the residue chromatographed over
silica gel. Fractions that eluted with EtOAc/hexane (2:3) gave
22 (209 mg, 60%). Fractions eluting with EtOAc/hexane (1:4)
afforded 2316 (35 mg, 9%) and the mixture of 24 and 25 (85.6
mg, 23%). Subsequent separation of the mixture by column
chromatography on silica gel using acetone/EtOAc/CH2Cl2 (1:
10:10) as eluent gave 24 (35 mg, 9%), 25 (20 mg, 5%), and
recovered mixture (35 mg, 9%).
(1R ,3S ,4S ,5S ,10R ,11R )-1-H yd r oxy-9-oxolon gip in -7-
en e (22): colorless crystals (ethanol); mp 173-174 °C; [R]589
+7°, [R]578 +7°, [R]546 +7°, [R]436 -7°, [R]365 -168° (c 0.15,
EtOH); UV (EtOH) λmax (log ꢀ) 226 (3.97) nm; IR νmax 3608,
3480 (OH), 1650 (CdC-CdO cycloheptenone), 1260 (C-O)
cm-1; 1H NMR (CDCl3, 300 MHz), see Table 2 and δ 1.84 (1H,
br s, OH); 13C NMR (CDCl3, 75.4 MHz), see Table 4; EIMS
m/z 234 [M]+ (3), 219 (18), 201 (24), 191 (24), 173 (96), 163
(48), 149 (60), 135 (100), 119 (85), 109 (85), 96 (56), 81 (71), 69
(31), 55 (31), 43 (49); HREIMS m/z 235.1696 (calcd for C15H22O2
+ H+, 235.1698).
(1R,3S,4S,5S,7R,10R,11R)-1,7-Dih yd r oxy-9-oxolon gip i-
n a n e (24): crystalline solid; mp 193-195 °C; [R]589 +12°, [R]578
+13°, [R]546 +15°, [R]436 +22°, [R]365 +32° (c 0.12, EtOH); IR
(CHCl3) νmax 3608, 3416 (OH), 1684 (CdO cycloheptanone)
cm-1; 1H NMR (CDCl3, 300 MHz), see Table 2 and δ 1.84 (1H,
br s, OH), 1.66 (1H, br s, OH); 13C NMR (CDCl3, 75.4 MHz),
see Table 4; EIMS m/z 252 [M]+ (3), 234 (5), 219 (13), 205 (7),
191 (25), 175 (24), 163 (34), 147 (28), 137 (50), 121 (60), 109
(61), 95 (100), 81 (34), 69 (43), 55 (20), 43 (48); HREIMS m/z
252.1729 (calcd for C15H24O3, 252.1725).
(1R,3S,4S,5S,7S,10R,11R)-1,7-Dih yd r oxy-9-oxolon gip i-
n a n e (25): colorless crystals (CHCl3/hexane); mp 188-190 °C;
[R]589 -12°, [R]578 -12°, [R]546 -14°, [R]436 -26°, [R]365 -43° (c
0.01, EtOH); IR (CHCl3) νmax 3602, 3435 (OH), 1684 (CdO
1
cycloheptanone) cm-1; H NMR (CDCl3, 300 MHz), see Table
2 and δ 2.11 (2H, br s, OH); 13C NMR (CDCl3, 75.4 MHz), see
Table 4; EIMS m/z 252 [M]+ (3), 234 (4), 219 (13), 205 (7), 191
(25), 175 (23), 163 (32), 147 (27), 137 (48), 121 (58), 109 (61),
95 (100), 81 (36), 69 (44), 55 (21), 43 (52); HREIMS m/z
252.1729 (calcd for C15H24O3, 252.1725).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-9-Ace t yloxy-1,7-d ih y-
d r oxylon gip in a n e (17): white solid; mp 136-138 °C; [R]589
+15°, [R]578 +16°, [R]546 +18°, [R]436 +32°, [R]365 +54° (c 0.15,
CHCl3); IR (CHCl3) νmax 3612, 3446 (OH), 1720 (CdO acetate),
1252 (C-O) cm-1; 1H NMR (CDCl3, 300 MHz), see Table 1 and
δ 2.06 (1H, br s, OH), 2.10 (3H, s, OAc), 1.70 (1H, br s, OH);
13C NMR (CDCl3, 75.4 MHz), see Table 4 and δ 170.9 (CdO
acetate), 21.3 (Me-acetate); EIMS m/z 296 [M]+ (0.2), 278 (1),
254 (2), 236 (15), 218 (22), 203 (49), 175 (56), 159 (49), 123
(65), 109 (89), 95 (98), 69 (74), 55 (39), 43 (100); HRDCIMS
(NH3) m/z 314.2334 (calcd for C17H28O4 + NH4+, 314.2331).
Oxid a t ion of t h e Mixt u r e of 12-14. A solution of the
12-14 mixture (700 mg, 2.1 mmol) in glacial AcOH (7 mL)
was treated with a solution of CrO3 (700 mg) in H2O (1 mL)
at 0 °C. The reaction mixture was stored at room temperature
for 2 h, poured over ice/H2O, and extracted with diethyl ether.
The organic layer was washed with H2O, dried over anhydrous
Na2SO4, and filtered. After solvent evaporation, the residue
was chromatographed on silica gel using EtOAc/hexane (1:4)
as eluent to give a mixture of 18-20 (475 mg, 68%) and
compound 21 (60 mg, 8%).
Rea ction of th e Mixtu r e of 18-20 w ith Alu m in a . A
solution of the mixture of 18-20 (475 mg, 1.4 mmol) in THF
(2 mL) was treated with 2.38 g of activated neutral alumina
(Brockmann l, 150 mesh, 58 Å, d ) 3.970 from Aldrich Co.).
After evaporation of the solvent with a steady stream of
nitrogen, H2O (1.5 mL) was added, and the impregnated
alumina was heated at 90 °C for 72 h; addition of H2O (1.5
mL) every 24 h was necessary. The reaction mixture was
brought to room temperature, THF was added, and the
alumina was filtered and washed repeatedly with EtOAc. The
resulting solution was evaporated, and the residue was chro-
matographed over silica gel eluting with EtOAc/hexane (4:1)
to give a mixture of 6 and 28 (258 mg, 66%), recovered 1816
(30 mg, 6%), and 22 (45 mg, 14%). Subsequent separation of
the mixture by repeated column chromatography on silica gel
using EtOAc/CH2Cl2 (1:24) as eluent gave 28 (250 mg, 64%)
and 6 (2 mg, 0.5%).
(1R,3S,4S,5S,10R,11R)-1-Acet yloxy-7-oxolon gip in -8-
en e (6): colorless oil; [R]589 +72°, [R]578 +76°, [R]546 +90°, [R]436

1408 J ournal of Natural Products, 2002, Vol. 65, No. 10
Mele´ndez-Rodrı´guez et al.
+206°, [R]365 +555° (c 0.18, CHCl3); UV (EtOH) λmax (log ꢀ) 244
(3.32) nm; IR (CHCl3) νmax 1724 (CdO acetate), 1652 (CdC-
CdO cycloheptenone), 1252 (C-O) cm-1; 1H NMR (CDCl3, 300
MHz), see Table 1 and δ 2.04 (3H, s, OAc); 13C NMR (CDCl3,
75.4 MHz), see Table 4 and δ 170.5 (CdO acetate), 21.3 (Me-
acetate); EIMS m/z 276 [M]+ (0.2), 234 (3), 216 (3), 201 (10),
188 (11), 173 (34), 145 (100), 131 (24), 119 (40), 96 (11), 81 (6),
67 (6), 55 (4), 43 (28); HREIMS m/z 276.1722 (calcd for
evaporated under a vacuum. The residue was dissolved in
CHCl3 and purified by repeated flash chromatography on silica
gel. Fractions that eluted with EtOAc/hexane (2:3) gave 30
(570 mg, 21%), a mixture of 31-32 (50 mg, 2%), and 33 (302.8
mg, 14%). Fractions eluting with EtOAc/hexane (3:2) afforded
34 (191 mg, 12%), 35 (165 mg, 10%), and 36 (70 mg, 4%). From
fractions that eluted with MeOH/EtOAc (1:19), unreacted
starting material 10 (96 mg, 10%) was recovered. Subsequent
separation of the mixture by flash chromatography on silica
gel using EtOAc/CH2Cl2 (1:24) was carried out giving 31 (20
mg, 1%) and 32 (29 mg, 1%).
C
17H24O3, 276.1725).
(1R,3S,4S,5S,10R,11R)-1-Acet yloxy-9-oxolon gip in -7-
en e (28): colorless crystals (acetone/hexane); mp 94-95 °C;
[R]589 -9°, [R]578 -10°, [R]546 -13°, [R]436 -49°, [R]365 -361° (c
0.15, CHCl3); UV (EtOH) λmax (log ꢀ) 226 (4.04) nm; IR (CHCl3)
νmax 1724 (CdO acetate), 1650 (CdC-CdO cycloheptenone),
1252 (C-O) cm-1; 1H NMR (CDCl3, 300 MHz), see Table 2 and
δ 2.02 (3H, s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table 4
and δ 170.6 (CdO acetate), 21.4 (Me-acetate); EIMS m/z 276
[M]+ (1), 261 (3), 234 (16), 216 (29), 201 (46), 188 (22), 173
(100), 145 (82), 109 (36), 96 (33), 81 (23), 69 (8), 55 (6), 43 (28);
HREIMS m/z 276.1722 (calcd for C17H24O3, 276.1725).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1,7,9-T r i-p -n it r o b e n -
zoyloxylon gip in a n e (30): yellow crystals (acetone/CH2Cl2);
mp 150-152 °C; [R]589 -62°, [R]578 -65°, [R]546 -76°, [R]436
-136°, [R]365 low energy (c 0.16, CHCl3); UV (CH3CN) λmax (log
ꢀ) 261 (4.33) nm; IR (CHCl3) νmax 1724 (CdO benzoates), 1608
(CdC aromatic), 1530, 1280 (NO2) cm-1; 1H NMR (CDCl3, 300
MHz), see Table 2 and δ 8.24 and 8.13 (12H, AA′BB′, H-4′,
4′′,4′′′,6′,6′′,6′′′ and H-3′,3′′,3′′′,7′,7′′,7′′′ p-nitrobenzoates); 13C
NMR (CDCl3, 75.4 MHz), see Table 4 and δ 164.4, 164.0, 163.8
(CdO benzoates), 150.5, 150.6, 150.6 (C-5′,5′′,5′′′), 135.8, 135.7,
135.6 (C-2′,2′′,2′′′), 130.6, 130.5, 130.4 (C-3′,3′′,3′′′ and C-7′,7′′,7′′′),
123.6, 123.6, 123.5 (C-4′,4′′,4′′′ and C-6′,6′′,6′′′); EIMS m/z 671
[M - (NO)]+ (1), 641 (0.1), 367 (30), 324 (4), 260 (3), 217 (29),
200 (66), 150 (100), 120 (48), 95 (9), 65 (5), 44 (6); HRFABMS
m/z 724.2155 (calcd for C36H35O12N3 + Na+, 724.2118).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1-H yd r oxy-7,9-d i-p -n i-
tr oben zoyloxylon gip in a n e (31): white solid: mp 222-223
°C; [R]589 +68°, [R]578 +71°, [R]546 +85°, [R]436 +188°, [R]365 low
energy (c 0.16, CHCl3); UV (CH3CN) λmax (log ꢀ) 261 (4.44) nm;
IR (CHCl3) νmax 3608, 3471 (OH), 1720 (CdO benzoates), 1608
(CdC aromatic), 1530, 1276 (NO2) cm-1; 1H NMR (CDCl3, 300
MHz), see Table 2 and δ 8.25 and 8.11 (4H, AA′BB′, H-4′,6′
and H-3′,7′ p-nitrobenzoate), 8.33 (4H, AA′BB′, H-3′′,7′′ and
H-4′′,6′′ p-nitrobenzoate), 1.87 (1H, br s, OH); 13C NMR (CDCl3,
75.4 MHz), see Table 4 and δ 164.7, 163.9 (CdO benzoates),
150.5, 150.5 (C-5′,5′′), 136.1, 135.7 (C-2′,2′′), 130.8, 130.5
(C-3′,3′′ and C-7′,7′′), 123.6, 123.5 (C-4′,4′′ and C-6′,6′′); EIMS
m/z 522 [M - (NO)]+ (2), 385 (6), 367 (5), 341 (6), 324 (6), 235
(5), 218 (93), 203 (18), 175 (47), 159 (16), 150 (100), 120 (31),
95 (14), 81 (5), 65 (1); HRDCIMS (NH3) m/z 570.2449 (calcd
for C29H32O9N2 + NH4+, 570.2452).
Acetyla tion of 10 w ith AcCl. A solution of 1016 (500 mg,
2.0 mmol) in acetone (20 mL) cooled in an ice bath was treated
with AcCl (0.3 mL, 4.2 mmol). The reaction mixture was stored
at room temperature for 24 h and then quenched and neutral-
ized by addition of an aqueous solution of KOH (6 N). The
acetone was removed under reduced pressure, and the crude
reaction product was extracted with EtOAc. The organic layer
was washed with H2O, dried over anhydrous Na2SO4, filtered,
and evaporated under a vacuum to give an oil. After purifica-
tion of the crude reaction mixture by flash chromatography
on silica gel, the mixture of 12-14 (104 mg, 16%) was obtained
from fractions that eluted with EtOAc/hexane (2:3). Fractions
eluting with EtOAc/hexane (4:1) and subsequent flash chro-
matography with the same eluent gave 15 (46 mg, 18%) and
29 (6 mg, 1%). Starting material 10 (59 mg, 12%) was
recovered from fractions eluting with MeOH/EtOAc (1:19).
(1R ,3S ,4S ,5S ,7R ,9R ,10S ,11R )-7-Ace t yloxy-9,11-d ih y-
d r oxyu r u a p a n e (29): colorless oil; [R]589 +6°, [R]578 +8°, [R]546
+8°, [R]436 +8°, [R]365 +8° (c 0.05, CHCl3); IR (CHCl3) νmax 3670,
1
3436 (OH), 1716 (CdO acetate), 1252 (C-O) cm-1; H NMR
(CDCl3, 300 MHz), see Table 2 and δ 2.03 (3H, s, OAc); 13C
NMR (CDCl3, 75.4 MHz), see Table 4 and δ 171.2 (CdO
acetate), 21.4 (Me-acetate); EIMS m/z 254 [M - (CH2dCdO)]+
(5), 236 (5), 221 (90), 203 (56), 194 (21), 177 (36), 161 (39), 147
(22), 137 (100), 121 (42), 109 (38), 96 (42), 81 (28), 69 (18), 55
(10), 43 (34); HRDCIMS (NH3) m/z 314.2333 (calcd for C17H28O4
+ NH4+, 314.2331).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-7-H yd r oxy-1,9-d i-p -n i-
tr oben zoyloxylon gip in a n e (32): yellow solid; mp 97-99 °C;
[R]589 -117°, [R]578 -123°, [R]546 -142°, [R]436 -281°, [R]365 low
energy (c 0.19, CHCl3); UV (EtOH) λmax (log ꢀ) 210 (sh) (4.00),
257 (4.35) nm; IR (CHCl3) νmax 3620, 3453 (OH), 1720 (CdO
1
Acetyla tion of 10 w ith AcCl a n d 4-(Dim eth yla m in o)-
p yr id in e in Aceton e a n d Su bsequ en t Oxid a tion a n d
Rea ction w ith Alu m in a . A solution of 1016 (500 mg, 2.0
mmol) and 4-(dimethylamino)pyridine (960 mg, 7.9 mmol) in
acetone (15 mL) cooled in an ice bath was slowly treated with
a solution of AcCl (0.3 mL, 4.2 mmol) in acetone (5 mL). The
reaction mixture was stored at room temperature for 24 h, and
the formed precipitate was filtered off and washed with EtOAc.
After the acetone was evaporated from the resulting solution,
the residue was extracted with EtOAc and worked up as
described for the acetylation of 10 with Ac2O, affording 1116
(182 mg, 24%), a mixture of 12-14 (218 mg, 33%), 15 (115
mg, 20%), 16 (42 mg, 7%), 17 (11 mg, 2%), and the unreacted
10 (59 mg, 12%). The mixture of 12-14 (200 mg, 0.6 mmol) in
AcOH (2 mL) was treated with CrO3 (200 mg) as described
above to yield 150 mg (75%) of a mixture of 18-20 and 35 mg
(17%) of 21. As described above, the mixture of 18-20 (150
mg, 0.5 mmol) in THF (1 mL) treated with neutral alumina
(750 mg) and H2O (0.5 mL, added every 24 h) yielded 7 mg
(6%) of 6, 50 mg (41%) of 28, 22 mg (15%) of the unreacted
18,16 and 21 mg (20%) of a mixture of 22 and 27.
benzoates), 1608 (CdC aromatic), 1530, 1282 (NO2) cm-1; H
NMR (CDCl3, 300 MHz), see Table 2 and δ 8.25-8.05 (8H, m,
H-3′,3′′,7′,7′′ and H-4′,4′′,6′,6′′ p-nitrobenzoate), 1.58 (1H, br
s, OH); 13C NMR (CDCl3, 75.4 MHz), see Table 4 and δ 164.0,
164.0 (CdO benzoates), 150.5, 150.5 (C-5′,5′′), 135.8, 135.7 (C-
2′,2′′), 130.4, 130.3 (C-3′,3′′ and C-7′,7′′), 123.6, 123.5 (C-4′,4′′
and C-6′,6′′); EIMS m/z 552 [M]+ (0.2), 522 (2), 385 (15), 367
(6), 341 (8), 260 (9), 218 (85), 175 (66), 150 (100), 96 (53), 69
(10), 43 (11); HREIMS m/z 552.2104 (calcd for C29H32O9N2
+
NH4+, 552.2108).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-9-H yd r oxy-1,7-d i-p -n i-
tr oben zoyloxylon gip in a n e (33): yellow crystals (acetone/
hexane); mp 223-225 °C; [R]589 -82°, [R]578 -86°, [R]546 -99°,
[R]436 -190°, [R]365 low energy (c 0.16, CHCl3); UV (CH3CN)
λmax (log ꢀ) 262 (4.26); IR (CHCl3) νmax 3602, 3480 (OH), 1720
(CdO benzoates), 1608 (CdC aromatic), 1530, 1272 (NO2)
cm-1 1H NMR (CDCl3, 300 MHz), see Table 3 and δ 8.25-
;
8.10 (4H, m, H-3′,3′′,7′,7′′ p-nitrobenzoate), 8.35-8.25 (4H, m,
H-4′,4′′,6′,6′′ p-nitrobenzoate), 2.15 (1H, br s, OH); 13C NMR
(CDCl3, 75.4 MHz), see Table 4 and δ 164.2, 164.1 (CdO
benzoates), 150.5, 150.4 (C-5′,5′′), 136.0, 135.9 (C-2′,2′′), 130.6,
130.5 (C-3′,3′′ and C-7′,7′′), 123.5, 123.4 (C-4′,4′′ and C-6′,6′′);
EIMS m/z 522 [M - (NO)]+ (5), 446 (0.7), 385 (4), 343 (9), 296
(4), 235 (5), 218 (47), 203 (35), 189 (24), 176 (67), 161 (43), 150
(98), 137 (35), 121 (100), 107 (37), 96 (31), 65 (6); HRDCIMS
(NH3) m/z 570.2445 (calcd for C29H32O9N2 + NH4+, 570.2452).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-7,9-Dih yd r oxy-1-p -n i-
tr oben zoyloxylon gip in a n e (34): yellow oil; [R]589 -35°, [R]578
Ester ifica tion of 10 w ith p-Nitr oben zoyl Ch lor id e. A
solution of 1016 (1 g, 4.0 mmol) and p-nitrobenzoyl chloride (1
g, 5.4 mmol) in anhydrous pyridine (25 mL) was stored at 4
°C for 24 h under an argon atmosphere. The reaction mixture
was poured over ice/H2O and extracted with EtOAc. The
organic layer was washed with dilute HCl (10%), H2O, aqueous
NaHCO3, and H2O, dried over anhydrous Na2SO4, filtered, and

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1409
-37°, [R]546 -43°, [R]436 -83°, [R]365 low energy (c 0.16, CHCl3);
UV (EtOH) λmax (log ꢀ) 212 (3.63), 259 (4.10) nm; IR (CHCl3)
νmax 3616, 3468 (OH), 1716 (CdO benzoate), 1608 (CdC
aromatic), 1530, 1280 (NO2) cm-1; 1H NMR (CDCl3, 300 MHz),
see Table 3 and δ 8.26 and 8.17 (4H, AA′BB′, H-4′,6′ and H-3′,7′
p-nitrobenzoate), 2.48 (2H, br s, OH); 13C NMR (CDCl3, 75.4
MHz), see Table 4 and δ 164.1 (CdO benzoate), 150.4 (C-5′),
136.1 (C-2′), 130.6 (C-3′ and C-7′), 123.4 (C-4′ and C-6′); EIMS
m/z 385 [M - (H2O)]+ (0.2), 373 (0.6), 260 (9), 236 (7), 218 (19),
203 (18), 175 (53), 150 (77), 121 (58), 107 (48), 95 (100), 81
(21), 69 (27), 55 (11), 43 (2); HRDCIMS (NH3) m/z 421.2320
(calcd for C22H29O6N + NH4+, 421.2339).
23%). Fractions eluting with EtOAc afforded 15 (12.5 mg, 3%),
and fractions eluting with MeOH/EtOAc (1:19) gave 10 (7.3
mg, 2%). Subsequent separation of the mixture by flash
chromatography on silica gel using acetone/EtOAc/CH2Cl2 (1:
6:14) gave 13 (263 mg, 63%) and 38 (13 mg, 2%).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1,9-Dia ce t yloxy-7-h y-
d r oxylon gip in a n e (13): colorless oil; [R]589 +8°, [R]578 +9°,
[R]546 +10°, [R]436 +19°, [R]365 +35° (c 0.35, CHCl3); IR (CHCl3)
νmax 3612, 3480 (OH), 1728 (CdO acetate), 1254 (C-O) cm-1
;
1H NMR (CDCl3, 300 MHz), see Table 1 and δ 2.09 (3H, s,
OAc), 2.03 (3H, s, OAc), 1.49 (1H, s, OH); 13C NMR (CDCl3,
75.4 MHz), see Table 4 and δ 170.8, 170.6 (CdO acetates), 21.4,
21.3 (Me-acetates); EIMS m/z 296 [M - (CH2dCdO)]+ (2), 278
(3), 263 (1), 236 (13), 218 (45), 203 (24), 185 (19), 175 (75), 159
(48), 147 (34), 133 (36), 123 (42), 107 (40), 96 (100), 81 (21), 69
(18), 55 (9), 43 (47); HRDCIMS (NH3) m/z 356.2437 (calcd for
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1,9-Dih yd r oxy-7-p -n i-
tr oben zoyloxylon gip in a n e (35): amorphous white solid
(CH2Cl2/hexane); mp 192 °C; [R]589 +10°, [R]578 +10°, [R]546
+13°, [R]436 +29°, [R]365 low energy (c 0.16, CHCl3); UV (EtOH)
λmax (log ꢀ) 210 (sh) (3.83), 259 (4.06) nm; IR (CHCl3) νmax 3604,
C
19H30O5 + NH4+, 356.2437).
3434 (OH), 1718 (CdO benzoate), 1608 (CdC aromatic), 1530,
1280 (NO2) cm-1; 1H NMR (CDCl3, 300 MHz), see Table 3 and
δ 8.28 and 8.19 (4H, AA′BB′, H-4′,6′ and H-3′,7′ p-nitroben-
zoate), 2.89 (2H, br s, OH); 13C NMR (CDCl3, 75.4 MHz), see
Table 4 and δ 164.3 (CdO benzoate), 150.5 (C-5′), 136.1
(C-2′), 130.6 (C-3′ and C-7′), 123.5 (C-4′ and C-6′); EIMS m/z
385 [M - (H2O)]+ (2), 373 (2), 284 (4), 257 (6), 236 (17), 218
(24), 203 (39), 175 (48), 150 (56), 137 (100), 120 (67), 109 (71),
95 (57), 81 (34), 69 (55), 57 (27), 43 (49); HRDCIMS (NH3) m/z
421.2346 (calcd for C22H29O6N + NH4+, 421.2339).
(1R,3S,4S,5S,7R,9R,10R,11R)-9-Acetyloxy-1-h yd r oxy-7-
p-n itr oben zoyloxylon gip in -a n e (38): pale yellow oil; [R]589
-13°, [R]578 -13°, [R]546 -14°, [R]436 -22°, [R]365 low energy (c
0.13, CHCl3); UV (EtOH) λmax (log ꢀ) 212 (sh) (3.82), 259 (4.04)
nm; IR (CHCl3) νmax 3606, 3504 (OH), 1732 (CdO acetate and
benzoate), 1608 (CdC aromatic), 1530, 1282 (NO2), 1254 (C-
1
O) cm-1; H NMR (CDCl3, 300 MHz), see Table 3 and δ 8.29
and 8.16 (4H, AA′BB′, H-4′,6′ and H-3′,7′ p-nitrobenzoate), 2.22
(3H, s, OAc), 1.65 (1H, br s, OH); 13C NMR (CDCl3, 75.4 MHz),
see Table 4 and δ 171.4 (CdO acetate), 164.0 (CdO benzoate),
150.5 (C-5′), 136.0 (C-2′), 130.6 (C-3′ and C-7′), 123.6 (C-4′ and
C-6′), 21.3 (Me-acetate); EIMS m/z 446 [M + 1]+ (0.2), 415 (2),
403 (7), 236 (35), 218 (100), 175 (77), 150 (57), 120 (61), 95
(51), 81 (33), 69 (25), 43 (46); HRDCIMS (NH3) m/z 463.2458
(calcd for C24H31O7N + NH4+, 463.2444).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1,7-Dih yd r oxy-9-p -n i-
tr oben zoyloxylon gip in a n e (36): white crystals (EtOAc/
hexane); mp 232-233 °C; [R]589 -7°, [R]578 -7°, [R]546 -8°, [R]436
-12°, [R]365 low energy (c 0.16, CHCl3); UV (EtOH) λmax (log ꢀ)
212 (3.93), 259 (4.24) nm; IR (CHCl3) νmax 3612, 3462 (OH),
1718 (CdO benzoate), 1608 (CdC aromatic), 1530, 1276 (NO2)
cm-1; 1H NMR (CDCl3, 300 MHz), see Table 3 and δ 8.28 and
8.20 (4H, AA′BB′, H-4′,6′ and H-3′,7′ p-nitrobenzoate), 1.82
(1H, br s, OH), 1.54-1.48 (1H, br s, OH); 13C NMR (CDCl3,
75.4 MHz), see Table 4 and δ 164.3 (CdO benzoate), 150.5
(C-5′), 136.0 (C-2′), 130.6 (C-3′ and C-7′), 123.5 (C-4′ and C-6′);
EIMS m/z 385 [M - (H2O)]+ (2), 236 (17), 218 (35), 203 (26),
193 (38), 175 (64), 159 (29), 150 (89), 137 (52), 121 (53), 107
(56), 96 (100), 81 (33), 69 (32), 55 (15), 43 (34); HRDCIMS
(NH3) m/z 421.2350 (calcd for C22H29O6N + NH4+, 421.2339).
(1R,3S,4S,5S,7R,9R,10R,11R)-1,9-Dia cet yloxy-7-p -n i-
tr oben zoyloxylon gip in a n e (37). A solution of 35 (600 mg,
1.5 mmol) in AcCl (3.5 g) was refluxed for 10 min. The AcCl
was removed by distillation, and the residue was extracted
with EtOAc. The organic layer was washed with a saturated
aqueous solution of NaHCO3 and H2O, dried over anhydrous
Na2SO4, filtered, and evaporated under vacuum. The residue
was chromatographed on silica gel using EtOAc/hexane (1:4)
as eluent to give 37 (807 mg, 95%) as a pale yellow oil: [R]589
-22°, [R]578 -22°, [R]546 -25°, [R]436 -38°, [R]365 low energy (c
0.15, CHCl3); UV (EtOH) λmax (log ꢀ) 258 (4.17) nm; IR (CHCl3)
νmax 1732 (CdO acetate), 1718 (CdO benzoate), 1608 (CdC
(1R,3S,4S,5S,7R,9R,10R,11R)-1-Acetyloxy-9-h yd r oxy-7-
p-n itr oben zoyloxylon gip in a n e (39): pale yellow oil; [R]589
-10°, [R]578 -10°, [R]546 -12°, [R]436 -19°, [R]365 low energy (c
0.04, CHCl3); UV (EtOH) λmax (log ꢀ) 212 (sh) (3.80), 259 (3.95)
nm; IR (CHCl3) νmax 3250 (OH), 1720 (CdO acetate and
benzoate), 1608 (CdC aromatic), 1530, 1280 (NO2), 1258
1
(C-O) cm-1; H NMR (CDCl3, 300 MHz), see Table 3 and δ
8.30 and 8.19 (4H, AA′BB′, H-4′,6′ and H-3′,7′ p-nitrobenzoate),
2.05 (3H, s, OAc), 1.60 (1H, br s, OH); 13C NMR (CDCl3, 75.4
MHz), see Table 4 and δ 170.8 (CdO acetate), 164.2 (CdO
benzoate), 150.5 (C-5′), 136.1 (C-2′), 130.6 (C-3′ and C-7′), 123.6
(C-4′ and C-6′), 21.5 (Me-acetate); EIMS m/z 445 [M]+ (0.1),
415 (1), 385 (1), 343 (3), 236 (7), 218 (51), 203 (35), 176 (65),
159 (45), 150 (46), 121 (100), 107 (51), 95 (45), 81 (20), 69 (27),
43 (33); HRDCIMS (NH3) m/z 463.2434 (calcd for C24H31O7N
+ NH4+, 463.2444).
Oxid a tion of 13. Using the procedure described above,
compound 13 (100 mg, 0.3 mmol) in AcOH (1 mL) was treated
with CrO3 (100 mg) to yield 72 mg (72%) of 19 and 13 mg (12%)
of 40.
(1R,3S,4S,5S,9R,10R,11R)-1,9-Dia cetyloxy-7-oxolon gip -
in a n e (19): colorless oil; [R]589 +1°, [R]578 +2°, [R]546 +3°, [R]436
+27°, [R]365 +121° (c 0.16, CHCl3); IR (CHCl3) νmax 1728
aromatic), 1530, 1282 (NO2), 1258 (C-O) cm-1 1H NMR
;
(CDCl3, 300 MHz), see Table 3 and δ 8.28 and 8.16 (4H,
AA′BB′, H-4′,6′ and H-3′,7′ p-nitrobenzoate), 2.17 (3H, s, OAc),
2.06 (3H, s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table 4
and δ 171.2, 170.6 (CdO acetates), 163.9 (CdO benzoate),
150.5 (C-5′), 136.0 (C-2′), 130.5 (C-3′ and C-7′), 123.5 (C-4′ and
C-6′), 21.4, 21.2 (Me-acetates); EIMS m/z 457 [M - (NO)]+ (11),
445 (14), 385 (6), 367 (7), 278 (7), 268 (14), 218 (55), 200 (46),
120 (100), 95 (16), 43 (14); HRDCIMS (NH3) m/z 505.2569
(calcd for C26H33O8N + NH4+, 505.2550).
(CdO acetate), 1720 (CdO cycloheptanone), 1228 (C-O) cm-1
;
1H NMR (CDCl3, 300 MHz), see Table 1 and δ 2.04 (3H, s,
OAc), 1.99 (3H, s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table
4 and δ 170.6, 170.5 (CdO acetates), 21.3, 21.0 (Me-acetates);
EIMS m/z 336 [M]+ (0.1), 308 (2), 294 (8), 277 (5), 234 (47),
216 (29), 188 (30), 173 (66), 159 (38), 145 (69), 123 (64), 96
(100), 83 (23), 69 (17), 55 (8), 43 (83); HRDCIMS (NH3) m/z
354.2273 (calcd for C19H28O5 + NH4+, 354.2280).
Alk a lin e Hyd r olysis of 37. A solution of 37 (600 mg, 1.2
mmol) in MeOH (38 mL) was treated with a 1.6 N solution of
KOH (7.5 mL). The reaction mixture was stored at room
temperature for 7 min and then neutralized by addition of
dilute HCl (20%). The MeOH was evaporated, and the residue
was extracted with EtOAc. The organic layer was washed with
H2O, dried over anhydrous Na2SO4, and filtered. The solvent
was evaporated under vacuum, and the residue was flash
chromatographed on silica gel. Fractions that eluted with
EtOAc/hexane (2:3) gave unreacted 37 (30 mg, 5%), 39 (7.5
mg, 1%), a mixture of 13 and 38 (295 mg), and 17 (84.5 mg,
(1R,3R,4S,5S,9R,10R,11R)-1,9-Dia cetyloxy-3-h yd r oxy-
7-oxolon gip in a n e (40): white solid; mp 143-145 °C; [R]589
+12°, [R]578 +16°, [R]546 +16°, [R]436 +36°, [R]365 +104° (c 0.03,
CHCl3); IR (CHCl3) νmax 3674 (OH), 1732 (CdO acetate), 1696
(CdO cycloheptanone), 1244 (C-O) cm-1; 1H NMR (CDCl3, 300
MHz), see Table 3 and δ 2.08 (3H, s, OAc), 2.01 (3H, s, OAc),
1.75 (1H, br s, OH); 13C NMR (CDCl3, 75.4 MHz), see Table 4
and δ 170.6, 170.4 (CdO acetates), 21.3, 21.1 (Me-acetates);
EIMS m/z 352 [M]+ (0.2), 334 (0.3), 310 (2), 292 (3), 274 (3),
250 (8), 232 (36), 214 (28), 189 (55), 171 (59), 161 (55), 147

1410 J ournal of Natural Products, 2002, Vol. 65, No. 10
Mele´ndez-Rodrı´guez et al.
(67), 133 (52), 123 (71), 109 (41), 95 (44), 83 (29), 69 (14), 55
(9), 43 (100); HREIMS m/z 352.1888 (calcd for C19H28O6,
352.1886).
Rea ction of 19 w ith Alu m in a . According to the procedure
for the reaction of 18-20 with alumina, 185 mg (0.6 mmol) of
19 adsorbed on neutral alumina (925 mg) with H2O (0.6 mL,
added each 24 h) yielded 132 mg (87%) of 6 and 6 mg (5%) of
27.
WINGX VI.6 crystallographic software package.36 In particu-
lar, the structure of 21 was solved by searching for a fragment
of known geometry by integrated Patterson using the computer
program PATSEE37 in combination with SHELXS-97.35
Crystallographic data for the structures reported in this
paper have been deposited with the Cambridge Crystal-
lographic Data Centre. Copies of the data can be obtained, free
of charge, on application to the Director, CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [fax: +44-(0)1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk].
(1R ,3S ,4S ,5S ,10R ,11R )-1-H yd r oxy-7-oxolon gip in -8-
en e (27): white solid; mp 100-102 °C; [R]589 -2°, [R]578 -2°,
[R]546 -2°, [R]436 -13°, [R]365 -83° (c 0.10, CHCl3); UV (EtOH)
λmax (log ꢀ) 250 (3.82) nm; IR (CHCl3) νmax 3608, 3462 (OH),
1650 (CdC-CdO cycloheptenone), 1258 (C-O) cm-1; 1H NMR
(CDCl3, 300 MHz), see Table 2 and δ 1.84 (1H, br s, OH); 13C
NMR (CDCl3, 75.4 MHz), see Table 4; EIMS m/z 234 [M]+ (0.3),
219 (3), 191 (4), 173 (14), 163 (13), 147 (17), 135 (31), 119 (100),
107 (21), 93 (40), 81 (11), 79 (11), 67 (13), 57 (12), 55 (12), 43
(1); HREIMS m/z 235.1698 (calcd for C15H22O2 + H+, 235.1698).
(1R,3S,4S,5S,7R,9R,10R,11R)-1,7-Dia cet yloxy-9-p -n i-
tr oben zoyloxylon gip in a n e (41). According to the procedure
described for 37, 300 mg (0.7 mmol) of 36 treated with AcCl
(1.5 g) afforded 41 (308.3 mg, 85%) as a yellow oil: [R]589 +3°,
[R]578 +3°, [R]546 +4°, [R]436 +19°, [R]365 low energy (c 0.16,
CHCl3); UV (EtOH) λmax (log ꢀ) 212 (3.68), 259 (4.06) nm; IR
(CHCl3) νmax 1732 (CdO acetate), 1714 (CdO benzoate), 1608
(CdC aromatic), 1530, 1282 (NO2), 1256 (C-O) cm-1; 1H NMR
(CDCl3, 300 MHz), see Table 3 and δ 8.33 and 8.26 (4H,
AA′BB′, H-4′,6′ and H-3′,7′ p-nitrobenzoate), 2.00 (3H, s, OAc),
1.98 (3H, s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table 4
and δ 170.4, 170.3 (CdO acetates), 164.4 (CdO benzoate),
150.3 (C-5′), 136.0 (C-2′), 130.6 (C-3′ and C-7′), 123.5 (C-4′ and
C-6′), 21.4, 21.1 (Me-acetates); EIMS m/z 457 [M - (NO)]+ (2),
367 (23), 324 (7), 278 (9), 260 (22), 218 (66), 200 (100), 185
(44), 175 (45), 150 (50), 137 (33), 120 (41), 95 (44), 81 (13), 43
P h otoch em ica l Ir r a d ia tion of (1R,3S,4S,5S,10R,11R)-
1-Acetyloxy-7-oxolon gip in -8-en e (6). The photoreaction was
carried out in a glass tube of 23 mm i.d. cooled with H2O at
room temperature using a Hanau (NK 620, 110V) low-pressure
Hg arc immersion lamp (254 nm) contained in a quartz jacket
(20 mm o.d.). A solution of 6 (30 mg, 0.1 mmol) in spectroscopic
grade cyclohexane (30 mL) was bubbled with argon before (20
min) and during the irradiation. The solution was irradiated
for 15 min, and then the solvent was evaporated. After four
runs, the combined residue was flash chromatographed on
silica gel using EtOAc/hexane (3:17) as eluent separating eight
1
fractions (I-VIII) on the basis of TLC analysis. The H NMR
spectrum of the main fraction IV (30 mg, 25%) showed a
mixture of three main rearranged compounds. This fraction
was dissolved in MeOH and separated by semipreparative
reversed-phase HPLC (Varian Dynamax, C18, 5 mm, 10 × 250
mm with a precolumn 5 mm, 10 × 50 mm; MeOH/H2O (65:
35), 3 mL/min; differential refractive index detector) to give 7
(6.1 mg, 5%), 8 (1.7 mg, 1%), and 9 (3.2 mg, 3%).
(1R,3S,4S,5S,8S,11R)-1-Acetyloxy-7-oxoqu ir og-9-en e (7):
colorless oil; [R]589 +576°, [R]578 +611°, [R]546 +717°, [R]436
+1528°, [R]365 +3678° (c 0.05, CHCl3); UV (EtOH) λmax (log ꢀ)
216 (3.77), 298 (2.79) nm; IR (CHCl3) νmax 1726 (CdO cyclo-
heptanone and acetate), 1252 (C-O) cm-1; HPLC tR 30 min;
1H NMR (CDCl3, 300 MHz), see Table 5 and δ 2.05 (3H, s,
OAc);
(33); HRDCIMS (NH3) m/z 505.2545 (calcd for C26H33O8
+
NH4+, 505.2550).
13C NMR (CDCl3, 75.4 MHz), see Table 5 and δ 170.4
(CdO acetate), 21.5 (Me-acetate); EIMS m/z 276 [M]+ (12), 248
(0.1), 233 (0.1), 216 (0.5), 188 (10), 173 (7), 161 (2), 145 (100),
131 (5), 119 (14), 105 (4), 93 (2), 72 (4), 55 (1), 43 (17); HREIMS
m/z 276.1726 (calcd for C17H24O3, 276.1725).
(1R ,3S ,4S ,5S ,7R ,9R ,10R ,11R )-1,7-Dia ce t yloxy-9-h y-
d r oxylon gip in a n e (14). According to the procedure described
for the alkaline hydrolysis of 37, 240 mg (0.5 mmol) of 41 in
MeOH (15 mL) was treated with a 1.6 N solution of KOH (3
mL) to give 43 mg (26%) of 14 as a pale yellow oil: [R]589 0°,
[R]578 0°, [R]546 0°, [R]436 +3°, [R]365 +8° (c 0.15, CHCl3); IR
(CHCl3) νmax 3600, 3502 (OH), 1728 (CdO acetate), 1254 (C-
(1R,3S,4R,5S,10R,11R)-1-Acet yloxy-7-oxop r en op s-8-
en e (8): colorless oil; [R]589 -150°, [R]578 -150°, [R]546 -186°,
[R]436 -429°, [R]365 -1036° (c 0.01, CHCl3); UV (EtOH) λmax
(log ꢀ) 210 (3.72), 290 (2.66) nm; IR (CHCl3) νmax 1726 (CdO
cycloheptanone and acetate), 1254 (C-O) cm-1; HPLC tR 42
min; 1H NMR (CDCl3, 300 MHz), see Table 5 and δ 2.06 (3H,
s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table 5 and δ 170.6
(CdO acetate), 21.3 (Me-acetate); EIMS m/z 276 [M]+ (10), 248
(0.1), 216 (0.5), 188 (9), 173 (7), 161 (2), 145 (100), 131 (5), 119
(14), 105 (3), 93 (2), 72 (4), 55 (1), 43 (16); HREIMS m/z
276.1726 (calcd for C17H24O3, 276.1725).
1
O) cm-1; H NMR (CDCl3, 300 MHz), see Table 1 and δ 2.05
(3H, s, OAc), 2.03 (3H, s, OAc), 1.90 (1H, br s, OH); 13C NMR
(CDCl3, 75.4 MHz), see Table 4 and δ 170.8, 170.8 (CdO
acetates), 21.4, 21.3 (Me-acetates); EIMS m/z 339 [M + 1]+
(0.1), 296 (0.1), 278 (2), 263 (2), 236 (12), 218 (41), 203 (41),
189 (28), 176 (82), 161 (59), 147 (46), 133 (41), 121 (100), 107
(59), 95 (55), 81 (19), 69 (27), 43 (51); HRDCIMS (NH3) m/z
356.2433 (calcd for C19H30O5 + NH4+, 356.2437).
(1R,3S,4S,5S,7R,10R,11R)-1,7-Dia cetyloxy-9-oxolon gip -
in a n e (20). According to the procedure described above, 20
mg (0.06 mmol) of 14 in AcOH (0.2 mL) treated with CrO3 (20
mg) afforded 16 mg (80%) of 20 as colorless crystals (MeOH):
mp 156-158 °C; [R]589 -22°, [R]578 -23°, [R]546 -27°, [R]436
-52°, [R]365 -109° (c 0.21, CHCl3); IR (CHCl3) νmax 1732, 1728
(1R,3R,5R,8S,11S)-1-Acetyloxy-7-oxopatzcu ar -9-en e (9):
colorless oil; [R]589 +329°, [R]578 +350°, [R]546 +412°, [R]436
+894°, [R]365 +2406° (c 0.03, CHCl3); UV (EtOH) λmax (log ꢀ)
208 (3.64), 305 (2.47) nm; IR (CHCl3) νmax 1764 (CdO cyclobu-
tanone), 1728 (CdO acetate), 1250 (C-O) cm-1; HPLC tR 34
min; 1H NMR (CDCl3, 300 MHz), see Table 5 and δ 1.97 (3H,
s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table 5 and δ 170.3
(CdO acetates), 1694 (CdO cycloheptanone), 1252 (C-O) cm-1
;
1H NMR (CDCl3, 300 MHz), see Table 1 and δ 2.05 (3H, s,
OAc), 2.03 (3H, s, OAc); 13C NMR (CDCl3, 75.4 MHz), see Table
4 and δ 170.4, 169.8 (CdO acetates), 21.2, 20.9 (Me-acetates);
EIMS m/z 336 [M]+ (0.5), 308 (2), 294 (3), 276 (11), 261 (4),
234 (50), 216 (81), 201 (49), 191 (39), 173 (78), 147 (57), 135
(48), 124 (85), 107 (60), 96 (100), 81 (25), 69 (28), 55 (13), 43
(93); HREIMS m/z 336.1938 (calcd for C19H28O5, 336.1937).
Sin gle-Cr ysta l X-r a y An a lysis. Single crystals of 21 and
25 were grown from CHCl3/hexane, while these of 22 and 28
from ethanol and acetone/hexane, respectively. X-ray data of
21, 22, 25, and 28 were collected on a Bruker Smart 6000 CCD
diffractometer. A total of 1321 frames were collected at a scan
width of 0.3° and an exposure time of 10 s/frame. The frames
were processed with the SAINT software package, provided
by the diffractometer manufacturer, by using a narrow-frame
integration algorithm, and the structure was solved and
refined by using the SHELXS-97 program35 included in the
(CdO acetate), 21.3 (Me-acetate); EIMS m/z 234 [M
-
(CH2dCdO)]+ (0.4), 206 (26), 189 (3), 173 (24), 163 (3), 146
(95), 131 (100), 121 (4), 105 (6), 91 (3), 69 (2), 57 (1), 43 (16);
HREIMS m/z 276.1726 (calcd for C17H24O3, 276.1725).
Ack n ow led gm en t. We thank Dr. Oscar R. Sua´rez-Castillo
(Centro de Investigaciones Qu´ımicas, Universidad Auto´noma
del Estado de Hidalgo) for X-ray data collection, and Dr. Luisa
U. Roma´n and Dr. J uan D. Herna´ndez (Instituto de Investi-
gaciones Qu´ımico-Biolo´gicas, Universidad Michoacana de San
Nicola´s de Hidalgo) for providing the plant material. Partial
financial support from CoNaCyT (Me´xico) is acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Atomic coordinates, bond
distances, bond angles, and crystallographic data of compounds 21,
22, 25, and 28 (S1-S17) are available free of charge via the Internet
at http://pubs.acs.org.

Quirogane, Prenopsane, and Patzcuarane Skeletons
J ournal of Natural Products, 2002, Vol. 65, No. 10 1411
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