Jiquilpane hydrocarbon skeleton generated by two successive Wagner-Meerwein rearrangements of longipinane derivatives

Article abstract of DOI:10.1021/np0201570

The molecular rearrangement of (1R,3S,4S,5S,7S,8R,9S,10R,11R)-7,8,9-triacetyloxylongipinan-1-ol (4) under acidic conditions afforded (1S,4R,5R,7S,8R,9S,10S)-7,8,9-triacetyloxyuruap-3(12)-ene (5), while 6, the C(3)-stereoisomer of 4, after two consecutive Wagner-Meerwein rearrangements followed by two 1,2-hydride migrations, afforded (4R,5R,7S,8S,9S,10S,11S)-7,8,9-triacetyloxyjiquilp-3(12)-ene (7), which possesses a new hydrocarbon skeleton. The structures of the new substances were elucidated by 1D and 2D NMR data in combination with X-ray diffraction analyses of the uruapane, longipinane, and jiquilpane derivatives 5, 6, and 14, respectively. Molecular modeling at the ab initio level was used to study the reaction mechanisms, while deuterium labeling was employed to confirm the C-C bond migrations and the hydride shifts.

Full text of DOI:10.1021/np0201570

1540
J . Nat. Prod. 2002, 65, 1540-1546
J iqu ilp a n e Hyd r oca r bon Sk eleton Gen er a ted by Tw o Su ccessive
Wa gn er -Meer w ein Rea r r a n gem en ts of Lon gip in a n e Der iva tives
Luisa U. Roma´n,† Carlos M. Cerda-Garc´ıa-Rojas,‡ Ramo´n Guzma´n,† Concepcio´n Armenta,†
J uan D. Herna´ndez,† and Pedro J oseph-Nathan*,‡
Instituto de Investigaciones Quı´mico-Biolo´gicas, Universidad Michoacana de San Nicola´s de Hidalgo, Apartado 137,
Morelia, Michoaca´n, 58000 Mexico, and 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
The molecular rearrangement of (1R,3S,4S,5S,7S,8R,9S,10R,11R)-7,8,9-triacetyloxylongipinan-1-ol (4)
under acidic conditions afforded (1S,4R,5R,7S,8R,9S,10S)-7,8,9-triacetyloxyuruap-3(12)-ene (5), while 6,
the C(3)-stereoisomer of 4, after two consecutive Wagner-Meerwein rearrangements followed by two
1,2-hydride migrations, afforded (4R,5R,7S,8S,9S,10S,11S)-7,8,9-triacetyloxyjiquilp-3(12)-ene (7), which
possesses a new hydrocarbon skeleton. The structures of the new substances were elucidated by 1D and
2D NMR data in combination with X-ray diffraction analyses of the uruapane, longipinane, and jiquilpane
derivatives 5, 6, and 14, respectively. Molecular modeling at the ab initio level was used to study the
reaction mechanisms, while deuterium labeling was employed to confirm the C-C bond migrations and
the hydride shifts.
One of the outstanding features of natural longipinene
derivatives, which can be isolated in good yields from Stevia
species,1,2 is their tendency to undergo molecular rear-
rangements to release the four-membered-ring strain.2 This
has been used to generate compounds with novel hydro-
carbon skeletons. In most cases, the rearrangements have
involved the seven-membered ring3-7 and, more recently,
the six-membered ring.8 To accomplish the latter, the
carbonyl group at C-1 was reduced to a hydroxyl group,
which is adjacent to the four-membered ring. Thus, p-
toluenesulfonic acid treatment of 1 afforded 2 and 3 (Fig-
ure 1), whose hydrocarbon skeleton was named urua-
pane.8 This transformation involves initial migration of the
C-5-C-11 bond to C-5-C-1, to afford carbocation 1a ,
followed by attack of the p-toluenesulfonate ion to give 3
or by two consecutive hydride shifts to generate olefin 2.
F igu r e 1. Molecular rearrangement of longipinane 1 to the urua-
In the present article we show that a stereochemical
change at C-3 in longipinane derivatives strongly affects
the rearrangement course, since acid treatment of triac-
etate alcohol 4 afforded uruapene 5, which is an analogue
of 2, while its C-3-stereoisomer 6 gave the sesquiterpenoid
7 arising after two consecutive C-C bond migrations
followed by two hydride shifts. The new hydrocarbon
skeleton present in 7 was named jiquilpane.
pane derivatives 2 and 3.
analysis. It is worth mentioning that the reaction with
Et2O‚BF3 substantially increased the yield and ease of
purification of olefin 5, as compared with the p-toluene-
sulfonic acid treatment.
To study the influence of stereochemical changes at C-3
in the longipinene system, alcohol 6 was prepared by
reduction of 99 and submitted to the rearrangement condi-
tions. That the hydroxyl group at C-1 in 6 was â was
established by X-ray diffraction (Figure 2). Et2O‚BF3 treat-
ment of 6 afforded a rearranged product (7) of molecular
formula C21H30O6, as indicated by HRMS. The 1H NMR
spectrum displayed signals for an exocyclic methylene
group at δ 4.87 and 4.62, three protons geminal to acetyloxy
groups at δ 5.38, 5.27, and 5.09, three acetyl groups at δ
2.16, 2.04, and 1.97, and three tertiary methyl groups at δ
1.15, 1.12, and 0.87. The 13C NMR spectrum showed
important differences as compared with that of 5. The
chemical shift differences on going from 5 to 7 were C-1
∆δ ) +5.5, C-2 ∆δ ) +3.0, C-3 ∆δ ) -5.4, C-4 ∆δ ) -1.0,
C-5 ∆δ ) +9.3, C-10 ∆δ ) -8.1, and C-11 ∆δ ) -5.3, as
Resu lts a n d Discu ssion
Since 2 was isolated as an oil,8 we devoted our efforts to
obtaining a crystalline derivative, suitable for X-ray analy-
sis. For this purpose, we induced the Wagner-Meerwein
rearrangement in alcohol 4, which was prepared by sodium
borohydride reduction of ketone 8.9 The â-configuration of
the hydroxyl group at C-1 in 4 followed from the coupling
constants of H-1, which were similar to those found in
alcohol 1. p-Toluenesulfonic acid or Et2O‚BF3 treatment of
4 gave olefin 5, as judged by NMR measurements. The
uruapane hydrocarbon skeleton of 5, whose perspective
view is depicted in Figure 2, was confirmed by X-ray
assigned by 2D experiments. The H and 13C NMR spectra
of the new compounds obtained in this work were fully
assigned by 2D spectroscopy including gCOSY, gHSQC,
gHMBC, and NOESY experiments.
1
* To whom correspondence should be addressed. Tel: (52-55) 5747-7112.
Fax: (52-55) 5747-7137. E-mail: pjoseph@nathan.chem.cinvestav.mx.
† Universidad Michoacana de San Nicola´s de Hidalgo.
‡ Centro de Investigacio´n y de Estudios Avanzados del Instituto Polite´c-
nico Nacional.
10.1021/np0201570 CCC: $22.00
© 2002 American Chemical Society and American Society of Pharmacognosy
Published on Web 09/11/2002

J iquilpane Hydrocarbon Skeleton
J ournal of Natural Products, 2002, Vol. 65, No. 11 1541
lyzed by X-ray diffraction. The X-ray structure of 14,
depicted in Figure 2, confirmed that this substance pos-
sesses a new hydrocarbon skeleton, which was named
jiquilpane.
The solid state conformation of the three rings of both
rearranged structures (5 and 14) was analyzed in terms of
the quantitative descriptors proposed by Cremer and
Pople.10 Table 1 lists the conformational parameters for
both structures, which were calculated with the RICON
program.11 Additionally, crystal data, collection, and refine-
ment parameters for structures 5, 6, and 14 are given in
Table 2.
It is reasonable to propose that formation of compound
5 (Figure 3) occurs through a pathway that resembles that
previously reported for 2.8 The hydroxyl group at C-1 of 4
coordinates to the Lewis acid to give 4a with the conse-
quent migration of the anti-periplanar C-5-C-11 bond to
form the C-5-C-1 bond. The carbocation at C-11 in 4b is
stabilized by a 1,3-hydride shift12 from H-2endo to H-11en-
do as in 4c. A subsequent 1,2-hydride shift12 from H-3exo
to H-2exo transfers the positive charge to C-3, giving the
tertiary carbocation 4d , which undergoes a proton loss from
C-12 to finally generate the C-3-C-12 double bond of 5.
On the other hand, when the stereochemistry at C-3 in the
longipinene derivatives is modified as in 6 (Figure 4), the
molecular rearrangement may initially proceed by a path-
way similar to that in the case of 4. Thus, intermediates
6a -c, which are epimeric species of 4a -c, respectively, can
be formed. However, when intermediate 6c is reached, the
reaction course undergoes a substantial modification. The
reason for this difference can be explained in terms of the
hydride migratory aptitudes in the norbornane skeleton,
since it is known12 that, while the 1,3-endo,endo-hydride
shift is a very favored process, the 1,2-endo,endo-hydride
shift is 200 times less favored than a 1,2-exo,exo-hydride
shift. Therefore, conversion of intermediate 6c into a
tertiary carbocation analogue of 4d by a 1,2-endo,endo-
hydride shift would be a nonpreferred process. Instead,
intermediate 6b, in equilibrium with 6c (pathway a), must
follow a lower energy pathway, which can proceed through
a second bond migration from C-2-C-1 to C-2-C-11
(pathway b), to give intermediate 6d , followed by a 1,3-
endo,endo-hydride shift from H-2endo to H-1endo, leaving
a carbocation at C-2 as in 6e. A subsequent energy-favored
1,2-hydride shift from H-3exo to H-2exo can give rise to
the tertiary carbocation 6f, which ultimately can undergo
a proton loss from C-12 to generate the jiquilpane deriva-
tive 7. The ab initio total energy for each reaction inter-
mediate in both epimeric series, calculated at the 3-21G(*)
level,13 is given in Figures 3 and 4. It is relevant to point
out that the calculated energy difference between inter-
mediate 6c and 6d is 24.94 kcal/mol (0.03975 hartree),
which explains why formation of intermediate 6d is a more
favored process than formation of 6c. Also, it is worth
mentioning that the energy difference between longipinane
derivative 4 and its C-3-stereoisomer 6 is quite large (2.39
kcal/mol, 0.00381 hartree), reflecting the strong steric
interaction between the methyl groups C-12 and C-15
present in 4 but of course absent in 6. Interestingly, the
energy difference between uruapane 5 and jiquilpane 7 was
only 0.60 kcal/mol (0.00095 hartree).
F igu r e 2. X-ray diffraction structures of the uruapane (5), longipinene
(6), and jiquilpane (14) derivatives.
The proposed mechanism for the formation of jiquilpane
derivative 7 (Figure 4) was studied by isotopic labeling
using deuterated derivatives. Thus, when 17, the C-1-
labeled analogue of 6, was submitted to the rearrangement
conditions, compound 15 showed that the deuterium atom
was incorporated at the methylene group C-1. The deute-
Since crystals of 7 were unsuitable for X-ray analysis,
the compound was hydrolyzed to give triol 12, which after
selective tosylation afforded monotosylate 13. Acetylation
of 13 provided 14, whose crystals were successfully ana-

1542 J ournal of Natural Products, 2002, Vol. 65, No. 11
Roma´n et al.
Ta ble 1. Comparative X-ray Conformational Parameters of Uruapane (5) and J iquilpane (14) Derivatives
b
b
compound (ring) (atoms)
Qa
φ2
θb
φ3
contribution of basic conformations
conformation
5 (A) (1-2-3-4-5)
6.08
5.65
9.61
0.62
0.58
1.80 89.28
envelope 97%; twist 3%
envelope 97%; twist 3%
boat 93%; twist-boat 6%; chair 1%
envelope
envelope
distorted boat
combination of twist chair, boat
and twist-boat
envelope
5 (B) (1-5-4-10-11)
5 (C) (1-2-3-4-10-11)
5 (D) (4-5-6-7-8-9-10)
9.09 46.76
324.14 boat 35%; twist-boat 20%;
chair 10%; twist-chair 36%
envelope 98%; twist 2%
envelope 84%; twist 16%
boat 93%; twist-boat 6%; chair 1%
311.43 boat 2%; twist-boat 44%; chair 42%; combination of twist-boat and chair
twist-chair 12%
14 (A) (2-3-4-10-11)
14 (B) (1-5-4-10-11)
14 (C) (1-5-4-3-2-11)
5.89
5.80
9.91
0.41
2.82
1.62 89.04
distorted envelope
distorted boat
14 (D) (4-5-6-7-8-9-10) 8.84 13.45
a
b
Total puckering amplitude in Å. In deg.
Ta ble 2. X-ray Data Collection and Processing Parameters for
5, 6, and 14
5
6
14
empirical formula
fw
C
21H30O6
C
21H32O7
C
26H34O7S
378.45
0.53 × 0.44
396.47
0.60 × 0.25
490.59
0.45 × 0.41
size (mm3)
× 0.38
× 0.20
× 0.36
cryst syst
space group
a (Å)
b (Å)
c (Å)
orthorhombic orthorhombic triclinic
P212121
7.6134(3)
16.5575(6)
17.3117(6)
90
P212121
9.118(2)
17.951(5)
13.358(4)
90
90
90
2186(1)
1.20
P1
8.3104(5)
9.2140(5)
9.5903(5)
106.794(1)
94.978(2)
105.388(2)
667.11(6)
1.22
R (deg)
â (deg)
γ (deg)
V (Å3)
90
90
2182.3(1)
1.15
Dcalcd (g cm-3
)
Z
4
4
1
F000
816
856
262
µ (mm-1
T (K)
)
0.08 (Mo KR) 0.74 (Cu KR) 0.16 (Mo KR)
293(2)
1.70-26.01
14570
298
293(2)
2.25-26.04
4528
3416
2.8
2θrange (deg)
total no. of reflns
no. of unique reflns 4294
Rint (%)
3-110
1651
1280
0.0
3.6
I g 3σ(I)
2838
365
0.937
3.9, 8.2
0.14
1196
278
1.089
6.2, 13.2
0.16
2114
347
0.915
4.7, 10.6
0.15
no. of params
goodness of fit (F2)
R (%), Rw (%)
Fmax (e Å-3
)
CCDC deposition no. 189570
189571
189572
rium position was determined from the 13C NMR spectra
of 15, where the carbon signal assigned to C-1 underwent
a substantial decrease due to the quadrupole moment and
C-D spin-spin coupling.14 The stereochemistry of the
1
deuterium atom was established by full analysis of the H
NMR spectrum of 15. The signal for H-1exo, found at δ
1.97 in 7, was not observed in 15, while the signal assigned
to H-1endo changed from a double doublet at δ 1.46
(J 1endo,1exo ) 12.7, J 1endo,5endo ) 9.8 Hz) in 7 to a doublet at
δ 1.43 (J 1endo,5endo ) 9.8 Hz) in 15. The small chemical shift
difference is due to a well-known isotope induced shift.15
When the epimeric longipinene derivative 4 was labeled
at C-1 to produce 19 and subjected to the rearrangement
conditions, the uruapane derivative 20 was formed. The
deuterium atom position was determined by comparing the
1H NMR spectrum of the nondeuterated analogue 5 with
that of 20, which showed the disappearance of the signal
at δ 2.33 assigned to H-1. Additionally, a substantial
decrease of the C-1 signal now at δ 38.4 in 20 confirmed
the position of the label.14 Interestingly, deuterium labeling
also showed that the methine C-1 in longipinene derivative
17 changes to a methylene in jiquilpane derivative 15,
while in the case of the uruapane derivative 20 the C-1
remains a methine as in its longipinene precursor 19.
On the other hand, to support the hydride migrations
during the formation of jiquilpane derivatives (Figure 4),
F igu r e 3. Reaction mechanism for the transformation of the lon-
gipinene derivative 4 into the uruapane derivative 5. [Ab initio
(3-21G*) energies in hartrees are in parentheses.]
alcohol 18, labeled at C-2, was prepared. Reaction of
rastevione acetate16 (10) with sodium in CH3OD followed
by treatment with acetic anhydride in pyridine gave
triacetate 11. Reduction of 11 with NaBH4 in MeOH
afforded alcohol 18, which under the rearrangement condi-
tions yielded 16, whose 13C NMR spectrum indicated the
presence of deuterium atoms at C-1 and C-2, as judged by
the drastic decrease14 of the signals at δ 36.0 and 32.9 when
compared to the same signals in the nondeuterated ana-
1
logue 7. The H NMR spectrum of 16, in comparison to 7,
was consistent with the deuterium labeling at H-1endo and
H-2endo, in further agreement with the proposed reaction
mechanism (Figure 4). Deuterium labeling was demon-
strated by the disappearance of the signal at δ 1.46,
assigned as H-1endo, in combination with the change of
the signal for H-5, from a double doublet at δ 1.74 (J 1endo,5
) 9.8 and J 1exo,5 ) 5.9 Hz) in 7 to a doublet at δ 1.73 (J 1exo,5

J iquilpane Hydrocarbon Skeleton
J ournal of Natural Products, 2002, Vol. 65, No. 11 1543
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 measured on a Perkin-Elmer 341
polarimeter. UV spectra were recorded on a Hitachi 200 spec-
trophotometer. IR spectra were recorded on a Perkin-Elmer
16F PC FT-IR or a Perkin-Elmer 599B spectrophotometer.
NMR spectra were measured from CDCl3 solutions using TMS
as the internal reference on Varian Gemini 200 or Varian
Mercury 300 spectrometers, operating at 200 or 300 MHz for
1H, respectively. Low-resolution mass spectra were recorded
at 20 eV on Hewlett-Packard 5989A or at 70 eV on Hewlett-
Packard 5989B or Saturn 2000 spectrometers. HRMS were
measured on a VG 7070 high-resolution mass spectrometer
at UCR Mass Spectrometry Facility, University of California,
Riverside. Elemental analyses were performed on a Perkin-
Elmer Series II CHNS 2400 analyzer. Organic layers were
dried using anhydrous Na2SO4. Column chromatography was
carried out on Merck silica gel 60 (70-230 mesh ASTM) and
TLC on Merck silica gel 60 F254 plates.
F igu r e 4. Reaction mechanism for the transformation of the lon-
gipinene derivative 6 into the jiquilpane derivative 7. [Ab initio
(3-21G*) energies in hartrees are in parentheses.]
) 5.9 Hz) in 16. In addition, the signal at δ 1.84 assigned
to H-2endo showed a decrease and the signal at δ 2.29
assigned to H-2exo was partially modified from a broad
doublet to a broad singlet, slightly shifted upfield (δ 2.26).
The present work illustrates that a minor stereochemical
change in appropriately functionalized longipinene deriva-
tives drastically affects the outcome of molecular rear-
rangements induced by acid treatment. The versatility
displayed by the tricyclic longipinene system can be used
for the preparation of new hydrocarbon structures, which
may be useful in the perfume industry,17 since several
related tricyclic sesquiterpenes possess appreciable odor-
iferous properties.18 Furthermore, the jiquilpane carbocyclic
skeleton is structurally closely related to culmorin and
longiborneol, which have been synthesized recently.19,20 In
particular, (-)-culmorin, isolated from Fusarium cul-
morum, possesses antifungal activity against several fungi
found in corn and wheat.21-23
(1R,3S,4S,5S,7S,8R,9S,10R,11R)-7,8,9-Tr ia cetyloxylon -
gip in a n -1-ol (4). A solution of triacetate 89 (400 mg) in MeOH
(10 mL) was treated with NaBH4 (250 mg) at room tempera-
ture for 15 min. The reaction mixture was poured over ice-
H2O and extracted with ether. The organic layer was washed
with H2O, dried, filtered, and evaporated. The residue was
crystallized from CHCl3-hexane, giving 4 (250 mg, 62%) as
tiny needles: mp 191-192 °C; [R]589 +11°, [R]546 +13°, [R]436
+18°, [R]365 +23° (c 0.20, CHCl3); IR (CHCl3) νmax 3608 (OH),
3466 (OH), 1732 (CdO), 1238 cm-1 (C-O); 1H NMR (200 MHz)
δ 5.32 (1H, d, J ) 10.8 Hz, H-7), 5.24 (1H, dd, J ) 10.8, 2.5
Hz, H-8), 5.19 (1H, d, J ) 2.5 Hz, H-9), 4.28 (1H, ddd, J ) 9.5,
5.6, 2.9 Hz, H-1), 2.55 (1H, ddd, J ) 15.2, 10.3, 9.5 Hz, H-2â),
2.50 (1H, br d, J ) 5.3 Hz, H-11), 2.16 (3H, s, OAc), 2.13 (1H,
d, J ) 5.3 Hz, H-4), 2.05 (3H, s, OAc), 2.05 (1H, m, H-3), 1.95

1544 J ournal of Natural Products, 2002, Vol. 65, No. 11
Roma´n et al.
(3H, s, OAc), 1.78 (1H, br, OH), 1.49 (1H, ddd, J ) 15.2, 7.1,
5.6 Hz, H-2R), 1.22 (3H, s, Me-15), 1.14 (3H, d, J ) 7.0 Hz,
Me-12), 1.01 (1H, s, H-5), 0.98 (3H, s, Me-13), 0.88 (3H, s, Me-
14); 13C NMR (50 MHz) δ 171.4 (OAc), 170.5 (OAc), 170.1
(OAc), 77.1 (C-9), 74.1 (C-1), 71.6 (C-7), 69.8 (C-8), 56.5 (C-5),
45.1 (C-4), 42.9 (C-11), 42.7 (C-10), 37.3 (C-3), 35.9 (C-2), 34.8
(C-6), 26.9 (C-14), 21.5 (C-12), 21.4 (C-15), 20.9 (OAc), 20.8
(OAc), 20.7 (OAc), 19.6 (C-13); EIMS m/z 396 [M]+ (0.1), 354
(54), 294 (20), 276 (33), 234 (100), 201 (31), 216 (65), 173 (40),
140 (35), 109 (36), 98 (68), 95 (47), 43 (43); HRDCIMS (NH3)
m/z 414.2501 (calcd for C21H32O7 + NH4+, 414.2492).
with hexane-EtOAc (9:1) afforded 7 as a white solid, which
was recrystallized from acetone-hexane to yield 7 (240 mg,
63%) as fine needles: mp 117-118 °C; [R]589 +19°, [R]578 +19°,
[R]546 +23°, [R]436 +38°, [R]365 +61° (c 0.20, CHCl3); IR (CHCl3)
ν
max 1738 (CdO), 1658 (CdC), 1240, (C-O), 884 cm-1; 1H NMR
(300 MHz) δ 5.38 (1H, d, J ) 11.0 Hz, H-7), 5.27 (1H, d, J )
2.4 Hz, H-9), 5.09 (1H, dd, J ) 11.0, 2.4 Hz, H-8), 4.87 (1H, br
s, H-12), 4.62 (1H, br s, H-12’), 2.56 (1H, s, H-4), 2.29 (1H, br
d, J ) 16.1 Hz, H-2exo), 2.16 (3H, s, OAc), 2.04 (3H, s, OAc),
1.97 (1H, m, H-1exo), 1.96 (3H, s, OAc), 1.91 (1H, t, J ) 4.4
Hz, H-11), 1.84 (1H, d, J ) 16.1 Hz, H-2endo), 1.74 (1H, dd, J
) 9.8, 5.9 Hz, H-5), 1.46 (1H, dd, J ) 12.7, 9.8 Hz, H-1endo),
1.15 (3H, s, Me-15), 1.12 (3H, s, Me-13), 0.87 (3H, s, Me-14);
13C NMR δ 169.7 (OAc), 169.3 (OAc), 168.9 (OAc), 154.3 (C-3),
103.8 (C-12), 77.9 (C-9), 72.1 (C-7), 70.4 (C-8), 54.6 (C-4), 53.9
(C-5), 50.7 (C-10), 44.4 (C-11), 38.1 (C-6), 36.0 (C-2), 32.9
(C-1), 26.9 (C-14), 23.7 (C-15), 23.2 (C-13), 21.4 (OAc), 21.3 (2
OAc); EIMS m/z 378 [M]+ (3), 318 (3), 276 (26), 258 (14), 216
(100), 173 (32), 145 (19), 107 (44), 94 (30), 43 (37); HREIMS
m/z 378.2027 (calcd for C21H30O6, 378.2042).
Tr ea tm en t of 6 w ith p-Tolu en esu lfon ic Acid . A solution
of 6 (100 mg) in C6H6 (24 mL) was treated with p-toluene-
sulfonic acid (160 mg) under reflux using a Dean-Stark trap
for 30 min and diluted with EtOAc. The organic layer was
washed with H2O, dried, filtered, and evaporated to dryness,
giving a dark oily residue, which was chromatographed. The
fractions eluted with hexane-EtOAc (9:1) afforded 7 (20 mg,
21%), identical to the sample obtained above.
(3R,4S,5S,7R,8R,9S,10R,11R)-7,8,9-Tr ia cetyloxy-2,2-d i-
d eu ter iolon gip in a n -1-on e (11). A solution of 1016 (500 mg)
in MeOD (4 mL) was treated with sodium (200 mg). The
reaction mixture was stored at room temperature for 2 days,
poured over ice-water, and extracted with EtOAc. The organic
layer was washed with H2O, dried, and evaporated. The
residue was dissolved in pyridine (1 mL) and treated with Ac2O
(1 mL). The reaction mixture was heated on a steam bath for
4 h. After workup as described for 14, the residue was
crystallized from CHCl3-hexane to yield 11 (60 mg, 14%): the
NMR spectral data were identical to those of the nondeuter-
ated analogue 99,16 except for the lack of the H-2R and H-2â
resonances. Also, the C-2 signal was not observed. EIMS m/z
354 [M - CH2CO]+ (6), 336 (5), 282 (23), 234 (24), 191 (14),
179 (17), 140 (54), 109 (34), 98 (95), 83 (100), 55 (24).
(4R,5R,7S,8S,9S,10S,11S)-7,8,9-Tr ih ydr oxyjiqu ilp-3(12)-
en e (12). A solution of 7 (100 mg) in MeOH (11 mL) was
treated with a solution of KOH (660 mg) in H2O (1.0 mL). The
mixture was refluxed for 2 h, concentrated to one-half volume,
poured over ice-H2O, and extracted with EtOAc. The organic
layer was washed with H2O, dried, filtered, and evaporated
to dryness, giving a pale yellow oily residue, which was
chromatographed. The fractions eluted with hexane-EtOAc
(3:2) afforded 12 (50 mg, 75%) as a white solid, which was
recrystallized from CHCl3-hexane as white needles: mp 109-
110 °C; [R]589 +50°, [R]578 +52°, [R]546 +58°, [R]436 +97°, [R]365
+152° (c 0.2, CHCl3); IR (CHCl3) νmax 3540 (OH), 1660 (CdC),
1220 cm-1 (C-O); 1H NMR (300 MHz) δ 4.80 (1H, br s, H-12),
4.56 (1H, br s, H-12’), 4.08 (1H, d, J ) 2.4 Hz, H-9), 3.64 (1H,
d, J ) 10.4 Hz, H-7), 3.54 (1H, dd, J ) 10.4, 2.4 Hz, H-8), 2.33
(1H, s, H-4), 2.22 (1H, d m, J ) 16.0 Hz, H-2exo), 2.19 (1H, t,
J ) 3.8 Hz, H-11), 1.82 (1H, m, H-1exo), 1.81 (1H, dt, J ) 16.0,
2.5 Hz, H-2endo), 1.66 (1H, dd, J ) 9.4, 6.4 Hz, H-5), 1.35 (1H,
dd, J ) 12.2, 9.4 Hz, H-1endo), 1.09 (3H, s, Me-15), 1.01 (3H,
s, Me-14), 0.97 (3H, s, Me-13); 13C NMR δ 155.4 (C-3), 102.7
(C-12), 79.1 (C-9), 73.2 (C-7), 71.8 (C-8), 54.4 (C-5), 54.1 (C-4),
50.4 (C-10), 43.4 (C-11), 38.2 (C-6), 36.2 (C-2), 32.7 (C-1), 27.4
(C-13), 25.0 (C-15), 22.1 (C-14); EIMS m/z 252 [M]+ (3), 234
(23), 201 (15), 173 (29), 145 (31), 121 (77), 107 (100), 93 (59),
69 (30), 43 (51); HREIMS m/z 252.1716 (calcd for C15H24O3,
252.1725).
(1S,4R,5R,7S,8R,9S,10S)-7,8,9-Tr ia cetyloxyu r u a p -3(12)-
en e (5). A solution of alcohol 4 (200 mg) in CH2Cl2 (2.4 mL)
was treated with boron triflouride etherate (0.6 mL). The
reaction mixture was stored at room temperature for 24 h,
poured over ice-water, and extracted with CH2Cl2. The organic
layer was washed with H2O, dried, and evaporated to dryness,
giving a yellow oily residue, which was chromatographed.
Fractions eluted with hexane-EtOAc (9:1) afforded a white
solid, which was recrystallized from CH2Cl2-hexane to yield
5 (105 mg, 55%) as white prisms: mp 138-139 °C; [R]589 -16°,
[R]578 -16°, [R]546 -19°, [R]436 -37°, [R]365 -63° (c 0.2, CHCl3);
IR (CHCl3) νmax 1742 (CdO), 1662 (CdC); 1240 (C-O), 884
1
cm-1 (CdC); H NMR (300 MHz) δ 5.38 (1H, d, J ) 10.8 Hz,
H-7), 5.18 (1H, dd, J ) 10.8, 4.0 Hz, H-8), 5.09 (1H, d, J ) 4.0
Hz, H-9), 4.85 (1H, br s, H-12), 4.67 (1H, br s, H-12’), 2.56 (1H,
br s, H-4), 2.38 (1H, dq, J ) 13.8, 2.4 Hz, H-11exo), 2.33 (1H,
m, H-1), 2.25 (1H, dsext, J ) 15.8, 2.4 Hz, H-2exo), 2.13 (3H,
s, OAc), 2.03 (3H, s, OAc), 1.94 (3H, s, OAc), 1.78 (1H, dt, J )
15.8, 2.4, H-2endo), 1.65 (1H, br s, H-5), 1.10 (3H, s, Me-13),
0.98 (3H, s, Me-14), 0.96 (3H, s, Me-15), 0.88 (1H, dd, J ) 13.8,
2.0 Hz, H-11endo); 13C NMR δ 170.1 (OAc), 169.0 (OAc), 168.6
(OAc), 148.9 (C-3), 105.4 (C-12), 75.6 (C-9), 71.3 (C-7), 68.6
(C-8), 63.2 (C-5), 53.6 (C-4), 42.6 (C-10), 39.1 (C-11), 39.0
(C-2), 38.4 (C-1), 37.1 (C-6), 29.3 (C-15), 26.8 (C-14), 24.1
(C-13), 21.4 (OAc), 21.2 (OAc), 21.1 (OAc); EIMS m/z 378 [M]+
(2), 318 (8), 276 (55), 258 (10), 234 (87), 216 (100), 188 (37),
173 (31), 145 (27), 121 (65), 107 (27), 94 (16), 43 (43); HREIMS
m/z 378.2055 (calcd for C21H30O6, 378.2042).
Tr ea tm en t of 4 w ith p-Tolu en esu lfon ic Acid . A solution
of 4 (25 mg) in C6H6 (6 mL) was treated with p-toluenesulfonic
acid (40 mg) under reflux using a Dean-Stark trap for 30 min
and diluted with EtOAc. The organic layer was washed with
H2O, dried, filtered, and evaporated to dryness, giving a dark
oily residue, which was chromatographed. The fractions eluted
with hexane-EtOAc (9:1) afforded 5 (3 mg, 12%), identical to
the sample obtained above.
(1R,3R,4S,5S,7S,8R,9S,10R,11R)-7,8,9-Tr ia cetyloxylon -
gip in a n -1-ol (6). A solution of triacetate 99,16 (400 mg) in
MeOH (10 mL) was treated with NaBH4 (250 mg) at room
temperature for 15 min. Workup as in the case of 4 yielded 6
(350 mg, 87%) as white needles: mp 159-160 °C; [R]589 -5°,
[R]578 -5°, [R]546 -6°, [R]436 -8°, [R]365 -12° (c 0.18, CHCl3);
IR (CHCl3) νmax 3600 (OH), 1745 (CdO), 1260 cm-1 (C-O); 1H
NMR (300 MHz) δ 5.35 (1H, d, J ) 10.8 Hz, H-7), 5.20 (1H,
dd, J ) 10.8, 3.3 Hz, H-8), 5.17 (1H, d, J ) 3.3 Hz, H-9), 4.28
(1H, dt, J ) 9.3, 3.4 Hz, H-1), 2.51 (1H, t, J ) 4.8 Hz, H-11),
2.40 (1H, m, H-3), 2.16 (3H, s, OAc), 2.05 (3H, s, OAc), 1.96
(1H, dd, J ) 5.8, 2.0 Hz, H-4), 1.94 (3H, s, OAc), 1.88 (1H,
ddd, J ) 15.9, 9.2, 2.9 Hz, H-2R), 1.78 (1H, ddd, J ) 15.9, 9.2,
5.5 Hz, H-2â), 1.70 (1H, br, OH), 1.20 (1H, s, H-5), 1.13 (3H,
s, Me-15), 0.97 (3H, s, Me-13), 0.96 (3H, d, J ) 6.6 Hz, Me-
12), 0.92 (3H, s, Me-14); 13C NMR (75.4 MHz) δ 170.2 (OAc),
169.3 (OAc), 169.0 (OAc), 76.4 (C-9), 73.5 (C-1), 71.8 (C-7), 69.8
(C-8), 49.4 (C-5), 44.9 (C-4), 43.5 (C-10), 42.6 (C-11), 35.8
(C-2), 34.8 (C-6), 30.4 (C-3), 27.6 (C-14), 21.4 (OAc), 21.4
(C-12), 21.3 (OAc), 21.2 (OAc), 20.9 (C-15), 20.2 (C-13); EIMS
m/z 354 [M - CH2CO]+ (6), 295 (5), 276 (32), 234 (100), 216
(60), 173 (34), 140 (30), 109 (34), 98 (56), 43 (43); anal. C
63.59%, H 8.16%, calcd for C21H32O7, C 63.63%, H 8.14%.
(4R,5R,7S,8S,9S,10S,11S)-7,8,9-Tr iacetyloxyjiqu ilp-3(12)-
en e (7). A solution of alcohol 6 (400 mg) in CH2Cl2 (4.8 mL)
was treated with boron triflouride etherate (1.2 mL) at room
temperature for 24 h. Workup as in the case of 5 gave a yellow
oily residue, which was chromatographed. Fractions eluted
(4R ,5R ,7S ,8S ,9S ,10S ,11S )-7,9-D i h y d r o x y -8-t o s y l-
oxyjiqu ilp -3(12)-en e (13). A solution of 12 (72 mg) in pyri-
dine (1.4 mL) was treated with p-toluenesulfonyl chloride (72
mg) at 4 °C for 24 h. The reaction mixture was poured over
ice-H2O and extracted with EtOAc. The organic layer was
washed with H2O, 10% HCl, H2O, aqueous NaHCO3, and H2O,

J iquilpane Hydrocarbon Skeleton
J ournal of Natural Products, 2002, Vol. 65, No. 11 1545
dried, filtered, and evaporated to dryness, giving a residue,
which was chromatographed. Fractions that eluted with
hexane-EtOAc (9:1) gave 13 (58 mg, 50%) as a colorless oil:
[R]589 +59°, [R]578 +59°, [R]546 +70°, [R]436 +134°, [R]365 +224°
resonance at δ 1.73 (1H, d, J ) 5.9 Hz) and of the H-2exo
resonance at δ 2.26 (1H, br s). Also, the C-1 and C-2 signals
were drastically decreased. EIMS m/z 380 [M]+ (8), 319 (5),
278 (28), 259 (20), 235 (44), 217 (100), 199 (29), 175 (41), 160
(27), 122 (48), 108 (70), 85 (39).
(c 0.14, CHCl3); UV (MeOH) λ
(log ꢀ) 225 (3.50) nm; IR
max
(CHCl3) νmax 3600 (OH), 1660 (CdC), 1605 (CdC, aromatic),
1100 (SdO), 1195 cm-1 (C-O); 1H NMR (200 MHz) δ 7.83 (2H,
d, J ) 8.0 Hz, OTs), 7.37 (2H, d, J ) 8.0 Hz, OTs), 4.84 (1H,
br s, H-12), 4.59 (1H, br s, H-12’), 4.54 (1H, dd, J ) 10.7, 2.3
Hz, H-8), 4.13 (1H, d, J ) 2.3 Hz, H-9), 3.84 (1H, d, J ) 10.7
Hz, H-7), 2.45 (3H, s, OTs), 2.32 (1H, s, H-4), 2.23 (1H, br d,
J ) 16.0 Hz, H-2exo), 2.17 (1H, t, J ) 3.8 Hz, H-11), 2.0 (1H,
br, OH), 1.78 (1H, dt, J ) 16.0, 2.5 Hz, H-2endo), 1.74 (1H, m,
overlapped, H-1exo), 1.64 (1H, dd, J ) 9.4, 6.4 Hz, H-5), 1.33
(1H, dd, J ) 12.4, 9.4 Hz, H-1endo), 1.00 (3H, s, Me-15), 0.95
(3H, s, Me-14), 0.92 (3H, s, Me-13); 13C NMR δ 156.0 (C-3),
145.4, 134.0, 130.1, 128.0 (OTs), 103.5 (C-12), 85.2 (C-8), 79.2
(C-9), 69.7 (C-7), 54.0 (C-4), 54.0 (C-5), 50.6 (C-10), 43.3
(C-11), 38.2 (C-6), 35.7 (C-2), 32.5 (C-1), 26.7 (C-13), 24.6
(C-15), 21.7 (OTs), 21.5 (C-14); EIMS m/z 234 [M - TsOH]+
(1), 216 (100), 201 (42), 187 (21), 173 (42), 148 (74), 131 (32),
119 (37), 105 (44), 91 (61); HRDCIMS (NH3) m/z 424.2163
(calcd for C22H30O5S + NH4+, 424.2158).
(1R,3R,4S,5S,7S,8R,9S,10R,11R)-7,8,9-Tr ia cet yloxy-1-
d eu ter iolon gip in a n -1-ol (17). A solution of triacetate 99,16
(400 mg) in MeOH (10 mL) was treated with NaBD4 (250 mg)
at room temperature for 15 min. After workup as in the case
of 6, the residue was crystallized from CHCl3-hexane to yield
17 (250 mg, 62%): the NMR spectral data were identical to
those of the nondeuterated analogue 6, except for the lack of
the H-1 signal and the change in multiplicity of H-11 at δ 2.51
(1H, d, J ) 4.8 Hz), H-2R at δ 1.88 (1H, dd, J ) 15.9, 9.9 Hz),
and H-2â at δ 1.78 (1H, dd, J ) 15.9, 5.5 Hz). Also, the C-1
signal was not observed. EIMS m/z 355 [M - CH2CO]+ (6),
295 (23), 277 (30), 235 (100), 217 (60), 174 (34), 140 (41), 98
(77), 83 (80), 43 (73).
(1R,3R,4S,5S,7R,8R,9S,10R,11R)-7,8,9-Tr ia cetyloxy-2,2-
d id eu ter iolon gip in a n -1-ol (18). A solution of 11 (200 mg)
in MeOH (3 mL) was treated with NaBH4 (50 mg) at room
temperature for 15 min. After workup as in the case of 6, the
residue was crystallized from CHCl3 to afford 18 (190 mg,
94%): the NMR spectral data were identical to those of 6
except for the lack of the H-2R and H-2â signals and the
change in multiplicity of the H-1 resonance at δ 4.28 (1H, br
d, J ) 3.5 Hz). Also, the signal for C-2 was not observed. EIMS
m/z 380 [M - H2O]+ (9), 320 (6), 278 (34), 260 (19), 236 (43),
218 (100), 175 (42), 161 (31), 122 (48), 108 (80), 85 (41).
(1R,3S,4S,5S,7S,8R,9S,10R,11R)-7,8,9-Tr ia cet yloxy-1-
d eu ter iolon gip in a n -1-ol (19). A solution of triacetate 89 (400
mg) in MeOH (10 mL) was treated with NaBD4 (100 mg) at
room temperature for 15 min. After workup as in the case of
4, the residue was crystallized from CHCl3-hexane to give 19
(380 mg, 94%): the NMR spectral data were identical to those
of the nondeuterated analogue 4, except for the lack of the
H-1 signal and the change in multiplicity of the H-2â resonance
at δ 2.55 (1H, dd, 15.2, 10.3 Hz), H-11 at δ 2.50 (1H, d, 5.3
Hz), and H-2R at δ 1.49 (1H, d, 15.2, 7.1 Hz). Also, the C-1
signal was not observed. EIMS m/z 397 [M]+ (0.2), 355 (7), 337
(3), 295 (20), 277 (41), 253 (22), 235 (100), 218 (23), 202 (27),
174 (40), 136 (36), 96 (46), 43 (35).
(1S ,4R ,5R ,7S ,8R ,9S ,10S )-7,8,9-T r ia c e t y lo x y -1-d e u -
ter iou r u a p -3(12)-en e (20). A solution of alcohol 19 (300 mg)
in CH2Cl2 (3.7 mL) was treated with boron trifluoride etherate
(0.9 mL). The reaction mixture was kept at room temperature
for 24 h. After workup as in the case of 5, the residue was
chromatographed by eluting with hexane-EtOAc (9:1). Frac-
tions 4-8 gave 20 (60 mg, 21%): the NMR spectral data were
identical to those of the nondeuterated analogue 5, except for
the lack of the H-1 signal and the change in multiplicity of
the H-11exo resonance at δ 2.39 (1H, dd, 13.9, 2.8 Hz) and
the H-2exo resonance at δ 2.25 (1H, dq, 15.8, 2.5 Hz). Also,
the C-1 signal was not observed. EIMS m/z 379 [M]+ (3), 319
(3), 277 (24), 259 (13), 217 (100), 174 (35), 146 (18), 108 (46),
94 (35), 43 (45).
(4R ,5R ,7S ,8S ,9S ,10S ,11S )-7,9-D ia c e t y lo x y -8-t o s y l-
oxyjiqu ilp -3(12)-en e (14). A solution of 13 (58 mg) in pyri-
dine (1 mL) was treated with Ac2O (1 mL). After 16 days, the
reaction mixture was poured over ice-H2O and extracted with
EtOAc. The organic layer was washed with 10% HCl, H2O,
aqueous NaHCO3 and H2O, dried, filtered, and evaporated,
giving a yellow residue, which was chromatographed. Frac-
tions eluted with hexane-EtOAc 19:1 yield 13 (10 mg, 14%)
as white needles: mp 148-151 °C; [R]589 -12°, [R]578 -16°,
[R]546 -16°, [R]436 -36°, [R]365 -62° (c 0.09, CHCl3); UV (MeOH)
λ
(log ꢀ) 226 (3.47) nm; IR (CHCl3) νmax 1740 (CdO), 1598
max
(Ph), 1220 (C-O), 1176 (SdO), 876 cm-1 (CdC); 1H NMR (300
MHz) δ 8.10 (2H, d, J ) 8.2 Hz, OTs), 7.33 (2H, d, J ) 8.2 Hz,
OTs), 5.39 (1H, d, J ) 10.6 Hz, H-7), 5.07 (1H, d, J ) 2.3 Hz,
H-9), 4.87 (1H, br s, H-12), 4.72 (1H, dd, J ) 10.6, 2.3 Hz,
H-8), 4.61 (1H, br s, H-12’), 2.44 (3H, s, OTs), 2.42 (1H, s, H-4),
2.23 (1H, br d, J ) 16.2 Hz, H-2exo), 2.08 (3H, s, OAc), 2.06
(3H, s, OAc), 1.90 (1H, m, H-1exo), 1.81 (1H, br s, H-11), 1.80
(1H, m, H2endo) 1.71 (1H, dd, J ) 9.8, 6.0 Hz, H-5), 1.44 (1H,
dd, J ) 13.1, 9.8 Hz, H-1endo), 1.15 (3H, s, Me-15), 0.96 (3H,
s, Me-13), 0.88 (3H, s, Me-14); 13C NMR δ 170.6 (OAc), 169.9
(OAc), 154.9 (C-3), 144.9, 134.2, 129.8, 127.8 (OTs), 104.3
(C-12), 78.3 (C-9), 78.2 (C-8), 70.8 (C-7), 54.5 (C-4), 53.4 (C-5),
50.4 (C-10), 43.9 (C-11), 37.9 (C-6), 35.4 (C-2), 32.6 (C-1), 26.4
(C-14), 22.8 (C-13), 22.8 (C-15), 21.6 (OTs), 20.9 (OAc), 20.7
(OAc); EIMS m/z 490 [M]+ (1), 448 (1), 430 (2), 387 (10), 335
(6), 319 (10), 275 (32), 259 (27), 233 (100), 216 (85), 198 (38),
187 (33), 173 (33), 155 (29); HREIMS m/z 490.2041 (calcd for
C
26H34O7S, 490.2025).
(4R ,5R ,7S ,8S ,9S ,10S ,11S )-7,8,9-Tr ia ce t yloxy-1-d e u -
ter iojiqu ilp -3(12)-en e (15). A solution of deuterated alcohol
17 (200 mg) in CH2Cl2 (2.4 mL) was treated with boron
triflouride etherate (0.6 mL). The reaction mixture was stored
at room temperature for 24 h. After workup as in the case of
7, the residue was chromatographed. Fractions eluting with
hexane-EtOAc (4:1) provided 15 (150 mg, 78%): the NMR
spectral data were identical to those of the nondeuterated
analogue 7 except for the lack of the H-1exo signal and the
change in multiplicity of the H-1endo resonance at δ 1.43 (1H,
d, J ) 9.8 Hz) and simplification of the H-11 and H-5 signals.
Also, the C-1 signal was not observed. EIMS m/z 379 [M]+ (2),
319 (3), 277 (27), 259 (13), 217 (100), 174 (35), 160 (20), 146
(19), 108 (46), 94 (32), 43 (39).
(4R,5R,7S,8S,9S,10S,11S)-7,8,9-Tr ia cetyloxy-1,2-d id eu -
ter iojiqu ilp -3(12)-en e (16). A solution of alcohol 18 (190 mg)
in CH2Cl2 (2.4 mL) was treated with boron triflouride etherate
(0.6 mL). The reaction mixture was kept at room temperature
for 24 h. After workup as in the case of 7 the residue was
chromatographed. Fractions eluted with hexane-EtOAc (4:1)
afforded 16 (100 mg, 55%): the NMR spectral data were
identical to those of 7 except for the lack of the H-1endo and
H-2endo signals and the change in multiplicity of the H-5
X-r a y Diffr a ction An a lyses. Single crystals of 5 were
grown by slow crystallization from CH2Cl2-hexane, while
those of 6 and 14 were grown by slow crystallization from
CHCl3-hexane. The X-ray data for 5 and 14 were collected
on a Bruker Smart 6000 CCD diffractometer. A total of 1321
frames were collected for each compound 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, using a narrow-frame integra-
tion algorithm. The X-ray data of 6, collected on a Nicolet R3m
diffractometer, were corrected for Lorentz and polarization
effects. The three structures were solved by direct methods
using the SHELXS-9724 program included in the WINGX
VI.625 crystallographic software package. For the structural
refinement, the non-hydrogen atoms were treated anisotropi-
cally, and the hydrogen atoms, included in the structure factor
calculation, were refined isotropically. Crystal data, collection,
and refinement parameters are given in Table 2.

1546 J ournal of Natural Products, 2002, Vol. 65, No. 11
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(25) Farrugia, L. J . J . Appl. Crystallogr. 1999, 32, 837-838.
(26) Clark, M.; Cramer, R. D., III; van Opdenbosch, N. J . Comput. Chem.
1989, 10, 982-1012.
(27) Burkert, U.; Allinger, N. L. Molecular Mechanics; ACS Monograph
177; American Chemical Society: Washington, DC, 1982.
Molecu la r Mod elin g Ca lcu la tion s. Geometry optimiza-
tions were achieved by using the MM2 force-field calculations
as implemented in the SYBYL26 molecular mechanics27 soft-
ware or using MMX as implemented in the PCMODEL
program. A systematic conformational search for the seven-
membered rings and the acetyl groups was carried out, with
the aid of Dreiding models, considering torsion angle move-
ments of ca. 30°. The EMM2 or EMMX values were used as the
convergence criterion to obtain the global minima. The mini-
mum energy molecular mechanics structures were submitted
to ab initio calculations employing the 3-21G(*) level of theory13
as implemented in the PC Spartan Pro program from Wave-
function, Inc. (Irvine, CA).
Ack n ow led gm en t. We are indebted to Dr. J . Mart´ın
Torres-Valencia for the elemental analysis determination of
6, to Dr. Oscar R. Sua´rez-Castillo (Centro de Investigaciones
Qu´ımicas, Universidad Auto´noma del Estado de Hidalgo) for
the raw X-ray data of 5 and 14, and to Q. F. B. Isa´ıas Tapia
for technical assistance (UMSNH). Partial financial support
from Conacyt (Mexico) is also acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Atomic coordinates, bond
distances, and bond angles for compounds 5, 6, and 14. This material
is available free of charge via the Internet at http://pubs.acs.org.
Refer en ces a n d Notes
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Colomb. Cienc. Ex. Fis. Nat. 1998, 22, 229-279; available on:
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83(nathan).html.
(2) Cerda-Garc´ıa-Rojas, C. M.; Pereda-Miranda, R. In Stevia: the Genus
Stevia; Medicinal and Aromatic Plants-Industrial Profiles, Vol. 19;
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86-118.
(3) Roma´n, L. U.; Herna´ndez, J . D.; del R´ıo, R. E.; Bucio, M. A.; Cerda-
Garc´ıa-Rojas, C. M.; J oseph-Nathan, P. J . Org. Chem. 1991, 56, 1938-
1940.
(4) Roma´n, L. U.; Herna´ndez, J. D.; Cerda-Garc´ıa-Rojas, C. M.; Dom´ınguez-
Lo´pez, R. M.; J oseph-Nathan, P. J . Nat. Prod. 1992, 55, 577-588.
(5) Roma´n, L. U.; Zepeda, L. G.; Morales, N. R.; Herna´ndez, J . D.; Cerda-
Garc´ıa-Rojas, C. M.; J oseph-Nathan, P. J . Nat. Prod. 1995, 58, 1808-
1816.
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