PAPER
FeCl3·6H2O as Catalyst for the Esterification of Steroid Alcohols
3409
Stigmasteryl Palmitate
Mp 106–107 °C.
IR (KBr): 1741 cm–1.
ceeded in 90% yield in 24 hours without isomerization of
the double bond moiety.
In summary, multivalent metal chlorides, especially,
FeCl3·6H2O is a versatile catalyst for esterification of ste-
roid alcohols with long-chain fatty acids.
1H NMR (500 MHz, CDCl3): d = 0.67 (3 H, s), 0.7–0.9 (14 H, m),
1.0 (9 H, m), 1.1–1.2 (3 H, m), 1.3 (28 H, br s), 1.38–1.74 (14 H, m),
1.83 (2 H, m), 1.92–2.08 (2 H, m), 1.92–2.08 (2 H, m), 2.27 (2 H, d,
J = 7.2 Hz), 2.30 (2 H, br d), 4.6 (1 H, m), 5.0 (1 H, dd, J = 9.0, 15.2
Hz), 5.1 (1 H, dd, J = 8.3, 11.0 Hz), 5.3 (1 H, br d).
13C NMR (125 MHz, CDCl3): d = 2.1, 12.3, 14.2, 19.1, 19.4, 21.1,
21.2, 21.3, 22.8, 24.4, 25.2, 25.5, 27.9, 29.0, 29.2, 29.3, 29.4, 29.5,
29.7, 29.8, 31.9, 32.0, 34.8, 36.7, 37.1, 38.2, 39.7, 40.6, 42.3, 50.1,
51.3, 56.0, 56.9, 73.7, 122.6, 129.4, 138.4, 139.8, 173.4.
Metal salts, stearic acid, palmitic acid, myristic acid, lauric acid, de-
canoic acid, octanoic acid, oleic acid, cholesterol, ergosterol, and
stigmasterol are commercially available and used without further
purification.1H and 13C NMR spectra were recorded at 500 and 125
MHz, respectively, on a JEOL ECA-500 NMR spectrometer. IR
spectra of solids were recorded on a Nexus 470 (Thermo Nicolet)
FT-IR spectrometer as KBr discs. Elemental analyses of all amides
were entrusted to measure at Center for Organic Elemental Mi-
croanalysis, Kyoto University.
Anal. Calcd for C45H78O2: C, 83.01; H, 12.07. Found: C, 82.76; H,
11.94.
Cholesteryl Oleate
IR (KBr): 1741 cm–1.
Esterification of Steroid Alcohols with Fatty Acids; General
Procedure
1H NMR (500 MHz, CDCl3): d = 0.67 (3 H, s), 0.80–0.94 (12 H, m),
0.94–1.21 (12 H, m), 1.21–1.40 (30 H, m), 1.40–1.66 (12 H, m),
1.78–1.88 (3 H, m), 1.93–2.05 (6 H, m), 2.23–2.34 (8 H, m), 4.56–
4.65 (1 H, m), 5.29–5.40 (3 H, m), 6.81 (1 H, s).
13C NMR (125 MHz, CDCl3): d = 11.9, 14.2, 18.8, 19.4, 21.1, 21.3,
22.6, 22.8, 22.9, 23.9, 24.4, 25.1, 27.3, 27.4, 27.9, 28.1, 28.3, 29.2,
29.3, 29.4, 29.6, 29.8, 29.9, 31.9, 32.0, 34.8, 35.9, 36.3, 36.9, 37.1,
38.3, 39.6, 39.8, 42.4, 50.1, 56.2, 56.8, 73.8, 122.7, 127.0, 129.8,
130.1, 137.8, 139.8, 173.4.
The esterification of steroid alcohols with fatty acids was carried
out in a single-necked round-bottomed flask (100 mL) equipped
with a Teflon-coated magnetic stirring bar and a Dean–Stark appa-
ratus surmounted with a reflux condenser. An equimolar amount of
each substrate, steroid alcohol and the fatty acid (6 mmol each), and
FeCl3·6H2O (16.2 mg, 0.06 mmol) in mesitylene (40 mL) were
charged into the round-bottomed flask. The mixture was heated to
reflux temperature with continuous removal of H2O. After 24 h, the
resulting mixture was cooled to r.t. The solvent was removed in vac-
uo, and the crude solid was purified by column chromatography us-
ing CHCl3 as an eluent (Table 2).
Anal. Calcd for C45H78O2: C, 83.01; H, 12.07. Found: C, 82.76; H,
12.06.
Cholesteryl Palmitate
Mp 80–81 °C.
Acknowledgment
IR (KBr): 1742 cm–1.
A part of this work was financially supported by a Grant-in Aid for
Scientific Research (B) 19310030, the Japan Society for the Promo-
tion of Science (JSPS).
1H NMR (500 MHz, CDCl3): d = 0.67 (3 H, s), 0.82–0.92 (12 H, m),
0.92–0.99 (2 H, m), 1.00 (3 H, s), 1.02–1.18 (6 H, m), 1.2 (28 H, br
s), 1.28–1.38 (6 H, m), 1.40–1.61 (10 H, m), 1.83 (3 H, m), 1.94–
2.04 (2 H, m), 2.25 (2 H, t, J = 7.6 Hz), 2.36 (2 H, m), 4.6 (1 H, m),
5.4 (1 H, br d).
References
(1) Kubo, K.; Takahashi, H.; Takeuchi, H. J. Oleo Sci. 2006, 55,
545.
(2) Srivastava, A. K.; Monohar, R.; Shukla, J. P. Mol. Cryst. Liq.
Cryst. 2006, 454, 627.
(3) Bunjes, H.; Rades, T. J. Pharm. Pharmacol. 2005, 57, 807.
(4) Ginsburg, G. S.; Atkinson, D.; Small, D. M. Prog. Lipid Res.
1985, 23, 135.
13C NMR (125 MHz, CDCl3): d = 11.9, 14.2, 18.8, 19.4, 21.1, 22.6,
22.8, 22.9, 23.9, 24.4, 25.2, 27.9, 28.1, 28.3, 29.2, 29.3, 29.4, 29.5,
29.6, 29.7, 29.8, 31.9, 32.0, 34.8, 35.9, 36.3, 36.7, 37.1, 38.2, 39.6,
39.8, 42.4, 50.1, 56.2, 56.8, 73.7, 122.7, 139.8, 173.4.
Anal. Calcd for C43H76O2: C, 82.63; H, 12.26. Found: C, 82.73; H,
12.18.
(5) Benz, G. In Comprehensive Organic Syntheses, Vol. 6;
Trost, R. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991,
Chap. 2.3, 381–417.
Ergosteryl Stearate
Mp 108–109 °C.
IR (KBr): 1742 cm–1.
(6) Otera, J. Esterification Methods, Reactions and
Applications; Wiley-VCH: Weinheim, 2003.
(7) (a) Hao, X.; Yoshida, A.; Nishikido, J. Tetrahedron Lett.
2004, 45, 781. (b) Ishihara, K.; Ohara, S.; Yamanmoto, H.
Science 2000, 290, 1140. (c) Ishihara, K.; Nakayama, K.;
Ohara, S.; Yamamoto, H. Tetrahedron 2002, 58, 8179.
(d) Bartoli, G.; Boeglin, J.; Bosco, M.; Locatelli, M.;
Massaccessi, M.; Melchiorre, P.; Sambri, L. Adv. Synth.
Catal. 2005, 347, 33. (e) Maki, T.; Ishihara, K.; Yamamoto,
H. Tetrahedron 2007, 63, 8645. (f) Sakakura, A.;
Nakarawa, S.; Ishihara, K. Nat. Protoc. 2007, 2, 1746.
(g) Wakasugi, K.; Misaki, T.; Yamada, K.; Tanabe, Y.
Tetrahedron Lett. 2000, 41, 5249. (h) Funatomi, T.;
Wakasugi, K.; Misaki, T.; Tanabe, Y. Green Chem. 2006, 8,
1022.
1H NMR (500 MHz, CDCl3): d = 0.62 (3 H, s), 0.78–0.92 (14 H, m),
0.92 (2 H, s), 1.02 (3 H, br d), 1.24 (40 H, s), 1.46 (1 H, m), 1.58 (4
H, m), 1.64–1.78 (2 H, m), 1.82–1.94 (4 H, m), 1.96–2.08 (2 H, m),
2.25–2.95 (2 H, m), 2.30–2.38 (1 H, m), 2.40–2.52 (1 H, m), 4.7 (1
H, m), 5.20–5.50 (2 H, m), 5.3 (1 H, br s), 5.5 (1 H, br s).
13C NMR (125 MHz, CDCl3): d = 12.1, 14.2, 16.3, 17.7, 19.7, 20.0,
21.1, 21.2, 22.8, 23.1, 25.1, 28.2, 28.4, 29.2, 29.3, 29.4, 29.5, 29.6,
29.7, 29.8, 32.0, 33.2, 35.0, 36.8, 37.2, 38.0, 39.1, 40.5, 42.9, 46.1,
54.6, 55.7, 72.5, 116.4, 120.2, 132.1, 135.6, 138.7, 141.5, 173.4.
Anal. Calcd for C46H78O2: C, 83.32; H, 11.86. Found: C, 83.57; H,
12.13.
Synthesis 2008, No. 21, 3407–3410 © Thieme Stuttgart · New York