Stereoselective entry to the bicycle [4.3.0] skeleton of oplopanes using a transannular cyclization strategy

Article abstract of DOI:10.1055/s-1999-3121

Treatment of budlein B with acid gave a H-4β, H-9α- oplopane via lactone cleavage, allylic rearrangement, transannular cyclization and pinacol-type rearrangement. This transformation is stereochemically complementary to that of schkuhfiolide, which produces a H-4α, H-9β- oplopane.

Full text of DOI:10.1055/s-1999-3121

1006
LETTER
Stereoselective Entry to the Bicycle [4.3.0] Skeleton of Oplopanes Using a
Transannular Cyclization Strategy
Guillermo Delgado,* Salvador Guzmán
Instituto de Química de la Universidad Nacional Autónoma de México. Circuito Exterior, Ciudad Universitaria. Coyoacán 04510. México,
D. F.
Fax +52(5)6162217; E-mail: delgado@servidor.unam.mx
Received 21 March 1999
Dedicated to Prof. Albert Eschenmoser
Abstract: Treatment of budlein B with acid gave a H-4b,H-9a-
oplopane via lactone cleavage, allylic rearrangement, transannular
cyclization and pinacol-type rearrangement. This transformation is
stereochemically complementary to that of schkuhriolide, which
produces a H-4a,H-9b-oplopane.
Key words: oplopanes, sesquiterpenes, cyclization, rearrangement,
stereoselectivity
The generation of carbocyclic compounds from
trans,trans-1(10),4-germacradienolides (germacrolides)
via acid catalyzed reactions has been topic of several stud-
ies.1 Such cyclizations can be utilized for the preparation
of elemanolides,2 eudesmanolides,3 guaianolides,4
xanthanolides5 and cyclobutane6 derivatives as the main
products, and these transformations are significantly giv-
ing support to the proposed biogenetic schemes.7 How-
ever, the acid catalyzed transformations of
melampolides,8 heliangolides9 and cis,cis-1(10),4-ger-
macradienolides were less studied compared with those of
trans,trans-1(10),4-germacradienolides,10 and their roles
in the biogenesis of polycyclic terpenoids remain uncer-
tain.
Since the configuration of the bicycle [4.3.0] nonane de-
pends on the conformation adopted by the cyclodecadiene
precursor during the transition state of the cyclization
(Scheme 1), it was decided to explore the scope of this re-
action with the isomers of the cyclodecadiene, and here
we report the results. Manganese dioxide oxidation of the
natural trans,trans-1(10),4-germacradienolide budlein B
We previously reported11 that acid treatment of the natural
melampolide schkuhriolide (1)12 gave mainly the epimers
2 and 3, 4,10 and the tricyclic compound 5. The formation
of the H-4a,H-9b-oplopanolide 5 can be rationalized via
an initial allylic rearrangement of 1 (to afford 2 and 3),
isomerization of the C(1)-C(10) double bond (to produce
4), transannular Michael type reaction and pinacol rear-
(6)14 afforded the aldehyde 7,15 which adopts a [1D14,15D5]
rangement, to afford the bicycle [4.3.0] nonane (Scheme
conformation16 both in the crystal and in solution. Acid
1). The yield of 5 was optimized to 85% from 1, and rep-
treatment of 7 (TFA in acetone) afforded allo-schkuhri-
resents an alternative entry to H-4a,H-9b-oplopano-
olide (8),17 previously obtained as natural product. 8 re-
mained unaffected in trifluoroacetic acid. Attempts to
relactonize budlein B (6) or the aldehyde 7 could not be
achieved, presumably by the preferential lactonization to
C-6 of the trans,trans-1(10),4-germacradienolides with
oxygens at C-6a and C-8b.18 When budlein B (6) was
treated with perchloric acid in acetone, a mixture of prod-
ucts was obtained, but using DME as solvent, the same
mixture was obtained with a major product (80%) which
was characterized as the H-4b,H-9a-oplopanolide 9.19
Additional products of the transformation were the H-
1a,H-5a-guaianolides vestenolide (10,20 4%), and ligus-
trin (11,21 8%). The formation of compound 9 can be ra-
lides.13
Scheme 1
Synlett 1999, S1, 1006–1008 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Stereoselective Entry to the Bicycle [4.3.0] Skeleton of Oplopanes
1007
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allylic rearrangement, to afford the cationic intermediate
at C(4) (intermediate A, Scheme 2), which is stabilized by
the addition of water to give the allylic tertiary alcohol (in-
termediate B, Scheme 2); protonation of the primary alco-
hol triggered the transannular cyclization and pinacol
rearrangement to produce the oplopane 9. At the same
time, protonation of the primary alcohol of 6 (intermedi-
ate C), followed by dehydration, allows the transannular
cyclization, which produces the C(1)-C(5)s bond, and the
cationic center at C(4) (intermediate D) is stabilized by
the addition of water (to form 10) or by loss of a proton (to
produce 11). The pseudoenantiomeric relationship of the
endocyclic double bonds in the key intermediates (4 in
Scheme 1 and B in Scheme 2) is reflected in the enantio-
meric fusion in the bicycle [4.3.0] nonane of the products
(5 and 9).
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(15) 7: White solid mp > 275 °C, UV λmax 205 (ε 28419); IR
(CHCl3) νmax 3453, 2980, 1759, 1658, 1412, 1355, 1286, 1142,
1090, 979 cm-1; 1H NMR (CDCl3, 200 MHz): δ 9.89 (1H, br
s, H-14), 6.40 (1H, br dd, J = 12 and 4 Hz, H-1), 6.33 (1H, d,
J = 3 Hz, H-13 cis), 5.60 (1H, d, J = 3 Hz, H-13 trans), 5.03
(1H, t, J = 10 Hz, H-6), 5.05 (1H, br d, J = 10 Hz, H-5), 4.56
(1H, br d, J = 6 Hz, H-8), 1.50 (3H, br s, H-15). 13C NMR
(CDCl3, 50 MHz, APT):192.9 (C-14), 169.9 (C-12), 156.6 (C-
1), 141.5 (C-10), 138.3 (C-4 (C-11)), 138.2 (C-11 (C-4)),
127.7 (C-5), 120.3 (C-13), 74.5 (C-6), 69.8 (C-8), 53.1 (C-7),
39.2 (C-2 (C-3)), 38.5 (C-3 (C-2)), 25.0 (C-9), 16.9 (C-15);
EIMS m/z (%) 262 (M+, 25), 244 (41), 215 (61), 137 (100),
105 (92), 81 (90), 41 (80); HRMS Calculated for: C15H18O4:
262.1205; Found: 262.1208.
Scheme 2
The results show that the tertiary alcohol at C-4 and the
1(10)-trans,5(6)-trans- double bonds in the intermediate
cyclodecadiene are the structural requirements for the
oplopane formation, and that the functionalities at C-8 and
C-14 determine the preferred conformations of the inter-
mediates, to produce diastereomeric products. In summa-
ry, transannular cyclizations of germacradienes provide
alternative, efficient synthetic entries to diastereomeric
(H-4a,H-9b and H-4b,H-9a) oplopanes.
Acknowledgement
We thank the technical staff from the Instituto de Química de la
UNAM: Rocío Patiño, María Isabel Chávez, Beatriz Quiroz, Luis
Velasco and Javier Pérez-Flores for spectroscopic measurements,
and Dr. Rubén A. Toscano for X-Ray analysis of 9.
References and Notes
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2734. (b) Macías, F. A.; Torres, A.; Molinillo, J. M. G.;
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1215. (c) Delgado, G.; Tejeda, V.; Salas, A.; Chávez, M. I.;
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(b) Fischer, N. H.; Olivier, E. J.; Fischer, H. D. Prog. Chem.
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1998, 39, 1401-1404.
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1008
G. Delgado, S. Guzmán
LETTER
H-6), 2.91 (1H, dddd, J = 10, 5, 1, 1, H-5), 2.87 (1H, dd,
Guzmán, S.; Bolaños, A.; Aguilar, M. I.; Navarro, V.;
Villarreal, M. L. J. Nat. Prod. 1998, 61, 1082-1085.
(18) In contrast, the preferential C-8 relactonization of trans,trans-
1(10),4-germacradienolides containing C-6 and C-8
J = 16, 3, H-7a), 2.75 (1H, ddd, J = 11, 10, 6, H-9), 2.48 (1H,
dd, J = 16, 5, H-7b), 2.10-2.14 (1H, m. H-1a), 2.07 (3H, s, H-
15), 2.01-2.05 (1H, m, H-3), 1.85 (1H, ddd, J = 12, 10, 10, H-
4); 1.77-1.66 (3H, m, H-1b, H-2a,b); 13C NMR (CDCl3, 125
MHz, HMQC, HMBC): 210.3 (C-14), 169.7 (C-12), 143.1 (C-
8), 139.5 (C-11), 121.8 (C-13), 108.7 (C-10), 78.0 (C-6), 57.4
(C-9), 48.2 (C-4), 47.7 (C-3), 47.1 (C-5), 36.6 (C-7), 21.9 (C-
1), 27.7 (C-15), 26.4 (C-2); EIMS m/z (%) 246 (M+, 9), 203
(48), 150 (35), 91 (44), 69 (55), 46 (100), 45 (60); HRMS
Calculated for: C15H18O3 246.1256, Found: 246.1252; Anal.
Calcd for C15H18O3: C 73.14, H 7.36, Found: C 73.04, H 7.51;
X-Ray analysis of 9 (to be published) confirmed the structure.
(20) Sachdev, K.; Kulshreshtha, D. K. J. Nat. Prod. 1985, 48, 249-
253.
lactonizable a-oxygen groups has been described: Yoshioka,
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1970, 148-149.
(19) To a stirred solution containing 25 mg (0.09 mmol) of budlein
B (6) in DME (20 mL) under N2 was slowly added HClO4
(Aldrich, 0.3 mL). The solution was stirred for 20 min at
55 °C. The reaction mixture was concentrated under reduced
pressure, diluted with EtOAc and washed exhaustively with
satd. aq. Na2CO3 and then with water, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The crude
oil obtained from six runs was subjected to column
chromatography and then to prep. TLC (mixtures of n-hexane-
EtOAc as elution system) to give, in order of increasing
polariry: ligustrin (11,21 8%), H-4b,H-9a-oplopanolide (9,
80%), vestenolide (10,20 4%). Minor additional products were
not characterized. 9: white solid: mp 132-134 °C; [α]D+205
(MeOH, c 0.102); UV λmax 208 (ε 12150); IR (CHCl3) νmax
2951, 1764, 1697, 1658, 1413, 1357, 1265, 1142, 1011, 895
cm-1; 1H NMR (CDCl3, 500 MHz, COSY): δ 6.09 (1H, d, J = 1
Hz, H-13 cis), 5.45 (1H, d, J = 1 Hz, H-13 trans), 4.92 (1H, br
s, H-10a), 4.83 (1H, br s, H-10b), 4.57 (1H, ddd, J = 5,5,3 Hz,
(21) (a) Romo, J.; Ríos, T., Quijano, L. Tetrahedron 1968, 24,
6087-6090. (b) Hernández, L. R.; Catalán, C. A. N.; Cerda-
García-Rojas, C. M.; Joseph-Nathan, P. Nat. Prod. Lett. 1995,
6, 215-221.
Article Identifier:
1437-2096,E;1999,0,S1,1006,1008,ftx,en;W10299ST.pdf
Synlett 1999, S1, 1006–1008 ISSN 0936-5214 © Thieme Stuttgart · New York