has been used for the synthesis of heliannuols D and A,5 which
in turn are believed to be involved in the allelopathic action of
sunflowers.
First Enantiospecific Synthesis of (-)-Parvifoline
and (-)-Curcuquinone
The construction of an eight-membered ring with a decon-
jugated double bond is the main structural feature that challenges
the synthesis of parvifoline 1. Also, introduction of chirality at
the nonfunctionalized benzylic position is difficult, as well. As
we have been interested in employing the renewable resources
of the nature for the synthesis of natural products, we have
identified citronellal as the key synthon, which is abundantly
available from plants and of synthetic origin, and have ac-
complished syntheses of laevigatin6 and herbertenol.7
Subhash P. Chavan,* Mahesh Thakkar,
Ganesh F. Jogdand, and Uttam R. Kalkote
DiVision of Organic Chemistry, Technology, National Chemical
Laboratory, Pune, India 411008
ReceiVed August 21, 2006
To our knowledge, four syntheses of rac-parvifoline have
been reported;8 three of them employed the Grob fragmentation
strategy for cyclooctane ring construction, and the other one
dealt with Dieckmann-type intramolecular cyclization of an ester
sulfone. Also, there are only four syntheses reported for optically
active curcuquinone 4.9 In this paper, we wish to report the
first enantiospecific synthesis of (-)-parvifoline 1 and (-)-
curcuquinone 4 starting from naturally occurring (R)-(+)-
citronellal. Here, we have used ring-closing metathesis as the
key step for the formation of the cyclooctene ring of (-)-
parvifoline 1, which efficiently places the double bond in the
right position.
As shown in the retrosynthetic analysis (Scheme 1), (-)-
parvifoline could be obtained from the diolefin 5, which in turn
could be obtained from (R)-(+)-citronellal. Accordingly, (R)-
(+)-citronellal (98% ee) was converted to enone 7 (1:1
diastereomeric mixture) as reported in the literature.10 Enone 7
was then treated with LDA as the base and quenched using
TMSCl to give the corresponding silyl enol ether of enone 7,
followed by oxidation using mCPBA11 to give trimethylsilyl
ether of R-hydroxy enone 8, which was further hydrolyzed by
HCl solution to furnish hydroxy enone 8 in 70% overall yield.
Enone 8 was then subjected to 1,2-addition using Grignard
reagent MeMgI to give the corresponding diol 9 as a diaster-
eomeric mixture, two of which could be separated by column
chromatography, in overall 95% yield. Both of the diastereomers
The first enantiospecific synthesis of (-)-parvifoline, em-
ploying ring-closing metathesis as the key step, and (-)-
curcuquinone from naturally occurring (R)-(+)-citronellal is
described.
The title compound parvifoline 1 along with isoparvifolinone
2 and parvifoline isovalerate 3 are sesquiterpenes, isolated from
genera Coreopsis1 and Perezia.2 These are the only examples
of naturally occurring compounds which contain a trimethyl
benzocyclooctane structural unit. The absolute configuration of
parvifoline 1 was determined3 by its chemical transformation
into (-)-curcuquinone 4, a natural product with known absolute
configuration.
(5) Takabatake, K.; Nishi, I.; Shindo, M.; Shishido, K. J. Chem. Soc.,
Perkin Trans. 1 2000, 1807-1808.
(6) Chavan, S. P.; Dhondge, V. D.; Patil, S. S.; Rao, T. S.; Govande, C.
A. Tetrahedron: Asymmetry 1997, 8, 2517-2518.
(7) Chavan, S. P.; Thakkar, M.; Kharul, R. K.; Pathak, A. B.; Bhosekar,
A. V.; Bhadbhade, M. V. Tetrahedron 2005, 61, 3873-3879.
(8) (a) Villagomez-Ibarra, R.; Joseph-Nathan, P. Tetrahedron Lett. 1994,
35, 4771-4772. (b) Grimm, E. L.; Levac, S.; Coutu, M. L. Tetrahedron
Lett. 1994, 35, 5369-5372. (c) Villagomez-Ibarra, R.; Alvarez-Cisneros,
C.; Joseph-Nathan, P. Tetrahedron 1995, 51, 9285-9300. (d) Covarrubias-
Zuniga, A.; Cantu, F.; Maldonado, L. A. J. Org. Chem. 1998, 63, 2918-
2921. (e) Bhowmik, D. R.; Venkateswaran, R. V. Tetrahedron Lett. 1999,
40, 7431-7433.
(9) (a) Ono, M.; Ogura, Y.; Hatogai, K.; Akita, H. Tetrahedron:
Asymmetry 1995, 6, 1829-1832. (b) Fuganti, C.; Serra, S. J. Chem. Soc.,
Perkin Trans. 1 2000, 3758-3764. (c) Takabatake, K.; Nishi, I.; Shindo,
M.; Shishido, K. J. Chem. Soc., Perkin Trans. 1 2000, 1807-1808. (d)
Yoshimura, T.; Kisyuka, H.; Kamei, T.; Takabatake, K.; Shindo, M.;
Shishido, K. ArkiVoc 2003, 247-255. (e) Minatti, A.; Heinz Dotz, K. J.
Org. Chem. 2005, 70, 3745-3748.
(-)-Curcuquinone 4 is an aromatic bisabolene sesquiterpe-
noid, which was isolated from the Caribbean gorgonian sea plum
Pseudoterogorgia rigida,4 and shows antibacterial activity. This
(1) Bohlmann, F.; Zdero, C. Chem. Ber. 1977, 110, 468-473.
(2) (a) Joseph-Nathan, P.; Hernandez, J. D.; Roman, L. U.; Garcia, G.
E.; Mendoza, V.; Mendoza, S. Phytochemistry 1982, 21, 1129-1132. (b)
Joseph-Nathan, P.; Hernandez, J. D.; Roman, L. U.; Garcia, G. E.; Mendoza,
V. Phytochemistry 1982, 21, 669-672. (c) Garcia, G. E.; Mendoza, V.;
Guzman B., J. A. J. Nat. Prod. 1988, 51, 150-151.
(3) (a) Joseph-Nathan, P.; Hernandez-Medel, M.; Martinez, E.; Rojas-
Gardida, M.; Cerda, C. M. J. Nat. Prod. 1988, 51, 675-689. (b) Garcia,
G. E.; Mendoza, V.; Guzman, B. A. J. Nat. Prod. 1987, 50, 1055-1058.
(4) McEnroe, F. J.; Fenical, W. Tetrahedron 1978, 34, 1661-1664.
(10) (a) Ghisalberti, E. L.; Jeferies, P. R.; Stuart, A. D. Aust. J. Chem.
1979, 32, 1627-1630. (b) Hagiwara, H.; Tomoyuki, O.; Ono, H.; Kamat,
V. P.; Hoshi, T.; Suzuki, T.; Ando, M. J. Chem. Soc., Perkin Trans. 1 2002,
895-900.
(11) Rubottom, G. M.; Gruber, J. M. J. Org. Chem. 1978, 43, 1599-
1602.
10.1021/jo061730d CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/13/2006
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J. Org. Chem. 2006, 71, 8986-8988