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S. Kopp et al.
LETTER
(15) Chiral auxiliary: Drewes, S. E.; Malissar, D. G. S.; Roos,
G. H. P. Chem. Ber. 1993, 126, 2663; details for the
synthesis of 10 will be published elsewhere.
Acknowledgment
We are indebted to Dr. Bernhard Pfeiffer for NMR support.
(16) (a) de Fátima, A. Synlett 2005, 1805. (b) Brestensky,
D. M.; Huseland, D. E.; McGettigan, C.; Stryker, J. M.
Tetrahedron Lett. 1988, 29, 3749.
References and Notes
(17) Mahoney, W. S.; Brestensky, D. M.; Stryker, J. M. J. Am.
Chem. Soc. 1988, 110, 291.
(18) Racemic aldehyde 13 has been prepared previously by
Bohlmann and Lonitz and found to be highly prone to
epimerization on silica gel.10
(1) (a) European Scientific Cooperative on Phytotherapy
(ESCOP) Monographs, 2nd ed.; Thieme: Stuttgart/ New
York, 2003, 539. (b) Kumar, V. Phytother. Res. 2006, 20,
1023.
(2) (a) Ziegler, G.; Ploch, M.; Miettinen-Baumann, A.; Collet,
W. Eur. J. Med. Res. 2002, 7, 480. (b) Taibi, D. M.; Petry,
H.; Landis, C. A.; Vitiello, M. V. Sleep Med. 2007, 11, 209.
(3) Schumacher, B.; Scholle, S.; Hölzl, J.; Khudeir, N.; Hess, S.;
Müller, C. E. J. Nat. Prod. 2002, 65, 1479.
(19) Preparation and Analytical Data of Compound 1
To a solution of ethyl ester 14 (32 mg, 0.12 mmol) in 2-
PrOH–H2O (5:1, 0.6 mL) was added LiOH (6 mg, 0.24
mmol), and the mixture was heated to 40 °C for 10 h. The
solution was concentrated and the residue directly purified
by FC (hexane–EtOAc = 5:1, 1% formic acid) to give 29 mg
(97%) of valerenic acid (1) as a white solid. Crystals suitable
for X-ray crystallography were obtained from hexane–
MeOH–Et2O.
(4) Marder, M.; Viola, H.; Wasowski, C.; Fernandez, S.;
Medina, J. H.; Paladini, A. C. Pharmacol. Biochem. Behav.
2003, 75, 537.
(5) Stoll, A.; Seebeck, E.; Stauffacher, D. Helv. Chim. Acta
1957, 40, 1205.
Mp 138.5–139.5 °C (lit.: 140–142 °C).10 [a]D25 –13.0 (c
(6) Khom, S.; Baburin, I.; Timin, E.; Hohaus, A.; Trauner, G.;
Kopp, B.; Hering, S. Neuropharmacology 2007, 53, 178.
(7) Benke, D.; Barberis, A.; Kopp, S.; Altmann, K.-H.;
Schubiger, M.; Vogt, K. E.; Rudolph, U.; Möhler, H.
Neuropharmacology 2009, 56, 174.
20
2.15, CHCl3); [a]D20 –119.8 (c 2.50, EtOH). {lit.: [a]D
–120.0, EtOH}.10 HRMS (EI): m/z calcd for C15H22O2:
234.1614; found [M]+: 234.1616. 1H NMR (400 MHz,
CDCl3, 25 °C): d = 7.16 (d, J = 9.8 Hz, 1 H), 3.58–3.52 (m,
1 H), 3.00–2.92 (m, 1 H), 2.21 (br t, J = 7.5 Hz, 2 H), 2.05–
1.96 (m, 1 H), 1.90 (s, 3 H), 1.89–1.73 (m, 3 H), 1.65 (br s,
3 H), 1.61–1.51 (m, 1 H), 1.47–1.39 (m, 2 H), 0.79 (d,
J = 7.0 Hz, 3 H). 13C NMR (100 MHz, CDCl3, 25 °C): d =
172.7, 146.2, 133.1, 131.2, 125.0, 47.4, 37.5, 34.6, 33.0,
28.8, 25.4, 24.5, 13.5, 12.1, 12.1. IR (neat): n = 2932, 2856,
2834, 1675, 1632, 1422, 1299, 1255, 901 cm–1.
(20) Natural valerenic acid was purchased from extrasynthèse
(France).
(8) Dietz, B. M.; Mahady, G. B.; Pauli, G. F.; Farnsworth, N. R.
Mol. Brain Res. 2005, 138, 191.
(9) Ramharter, J.; Mulzer, J. Org. Lett. 2009, 11, 1151.
(10) Bohlmann, F.; Lonitz, M. Chem. Ber. 1980, 113, 2410.
(11) (a) Minami, T.; Usunomiya, T.; Nakamura, S.; Okubo, M.;
Kitamura, N.; Okada, Y.; Ichikawa, J. J. Org. Chem. 1994,
59, 6717. (b) Baudouy, R.; Sartoretti, J. Tetrahedron 1983,
39, 3293. (c) Joseph, K. T.; Krishna Rao, G. S. Tetrahedron
1967, 23, 3215.
(12) Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011.
(13) Lee, H. W.; Ji, S. K.; Lee, I.-Y. C.; Lee, J. H. J. Org. Chem.
1996, 61, 2542.
(21) The structural data have been deposited with the Cambridge
Crystallographic Data Centre. Deposition No. CCDC
719101.
(22) Bal, B. S.; Childers, W. E. Jr.; Pinnick, H. W. Tetrahedron
1981, 37, 2091.
(14) The pulegone used in our experiments was purchased from
ACROS ORGANICS and was 92% pure (pract. grade)
according to the supplier.
Synlett 2009, No. 11, 1769–1772 © Thieme Stuttgart · New York