Russian Chemical Bulletin, International Edition, Vol. 59, No. 1, pp. 302—303, January, 2010
302
An efficient synthesis of cholesterol formate
A. M. Vasil´tsov, A. I. Mikhaleva, A. V. Ivanov, E. V. Skital´tseva, and B. A. Trofimov
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
1 ul. Favorskogo, 664033 Irkutsk, Russian Federation.
Fax: +7 (395 2) 41 9346. Eꢀmail: boris_trofimov@irioch.irk.ru
Scheme 1
Cholesterol formate is an important compound in the
chemistry of steroids. It is used in biochemical investigaꢀ
tions of model membrane vesicles.1 Recently, cholesterol
formate has been isolated from the red alga Grateloupia
turuturu Yamada and this may be of chemotaxonomic sigꢀ
nificance for this organism.2 This compound is employed
as a component in liquidꢀcrystal optical filters.3 Formyl
protection is widely used in cholesterol chemistry because
of its selective removal under mild conditions (K2CO3,
methanol, 20 °C) in the presence of other ester protecting
groups.4 That is why a search for new convenient routes to
cholesterol formate is of relentless interest.
Common reagents employed for Oꢀformylation of choꢀ
lesterol include DMF—benzoyl chloride,5 DMF—triꢀ
arylphosphine—halogen,6 EtOCHO—Cu(NO3)2•3H2O,7
MeOCHO—Ph3P—CBr4,8
CCl3CHO—K2CO3,9
i. DMF—oxalyl chloride, CH2Cl2
EtOCHO—PCl3—SiO2),10 and DMF—POCl3.11 Usualꢀ
ly, they are used in large molar excesses with respect to
cholesterol. For instance, formylation of cholesterol with
DMF—POCl3 (the Vilsmeier complex), which is poorly
reproducible and inefficient for alcohols,5 is carried out in
the presence of its fourꢀ to fivefold molar excess (~20 °C,
3 h, 64% yield).11
(5×10 mL). The organic layer and the extracts were washed with
saturated aqueous NaHCO3 (3×10 mL) and water (3×10 mL)
and dried with MgSO4. Column chromatography on neutral
Al2O3 in hexane—ether (2 : 1) gave cholesterol formate (1.05 g,
97%) as white crystals, m.p. 112—113 °C (cf. Ref. 11: 112—113
°C). Found (%): C, 81.23; H, 11.14. C28H46O2. Calculated (%):
C, 81.10; H, 11.18. The 1H and 13C NMR and IR spectra of the
compound obtained are identical with those cited in Ref. 11.
Thus, the complex DMF—oxalyl chloride is a highly
In our recent synthesis of 1ꢀvinylpyrroleꢀ2ꢀcarbaldeꢀ
hydes,12 we found that the complex DMF—oxalyl chloꢀ
ride is a milder and more efficient formylating reagent
than the classic Vilsmeier system.
Our investigations in the borderland between the chemꢀ
istry of pyrroles and steroids,13 including novel approachꢀ
es to their vinylation14 and formylation,12,15 led us to a conꢀ
venient and efficient route to cholesterol formate. At a molar
ratio cholesterol : DMF—oxalyl chloride of 1 : 1.5, the reꢀ
action in CH2Cl2 at ~20 °C is completed in 40 min to give
the target product in 97% yield (Scheme 1).
efficient and economical reagent for formylation of choꢀ
lesterol as well.
This work was financially supported by the Council on
Grants at the President of the Russian Federation (Proꢀ
gram for State Support of Leading Scientific Schools of
the Russian Federation, Grant NShꢀ263.2008.3).
References
Cholesterol formate. Dimethylformamide (0.29 g, 3.9 mmol)
and (COCl)2 (0.49 g, 3.9 mmol) were mixed at 0—5 °C. After
10 min, CH2Cl2 (15 mL) and a solution of cholesterol (1.0 g,
2.6 mmol) in CH2Cl2 (15 mL) were added at room temperature
to the resulting crystalline complex. The reaction mixture was
stirred at room temperature for 30 min. The excess of the reagent
was decomposed with a solution of NaOAc (1.3 g) in water
(35 mL) for 30 min. The organic layer was separated and organic
materials from the aqueous layer was extracted with CH2Cl2
1. J. Wang, Megha, E. London, Biochemistry, 2004, 43, 1010.
2. E. Plouguerné, H. Kikuchi, Y. Oshima, E. Deslandes,
V. StigerꢀPouvreau, Biochem. Syst. Ecol., 2006, 34, 714.
3. US Pat. 3 679 290 (1972); Chem. Abstr., 1973, 77, P 95289c.
4. T. W. Greene, P. G. M. Wuts, Protective Groups in Organic
Synthesis, 3rd ed., Wiley, New York, 1999, 747 pp.
5. J. Barluenga, P. J. Campos, E. GonzalezꢀNuñez, G. Asenꢀ
sio, 1985, Synthesis, 426.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 293—294, January, 2010.
1066ꢀ5285/10/5901ꢀ0302 © 2010 Springer Science+Business Media, Inc.