Organic compounds -- part of the class 532-570 series – Organic compounds – Cyclopentanohydrophenanthrene ring system containing
Patent
1995-08-14
1997-11-11
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Cyclopentanohydrophenanthrene ring system containing
C07J 900
Patent
active
056866364
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP93/01823 filed Dec. 16, 1993.
FIELD OF THE INVENTION
The present invention relates to a process for preparing high-purity cholesterol from impurities-containing crude cholesterol by selective reduction of said impurities to cholesterol.
PRIOR ART
The cholesterol widely used in the fields of medicines, cosmetics and livestock feeds is produced from wool grease, fish oils or brains of higher animals, and mostly from wool grease.
Known processes for preparing cholesterol from wool grease include a solvent extraction based on a difference in solubility, an adduct method utilizing a low solubility of an adduct of cholesterol with a metal, column chromatography, etc. However, since these methods, if practiced singly, fail to produce fully purified products, currently the cholesterol prepared by each method is concentrated and finally recrystallized to improve the purity.
The purity of said cholesterol is specified as equivalent to a melting point of 147.degree. to 150.degree. C. in the Japanese Pharmacopoeia and in the U.S. NF. Commercially available cholesterols (24 samples) have a purity in the range of 90.7 to 96.3% as determined by assay through GLC.
In recent years, researches have been actively conducted on drug delivery system in the medical field. Currently investigations are being made into, as one of the system means, liposomes having a medicament covered with a membrane composed of phospholipid and cholesterol. In this connection, the purity of cholesterol useful as the starting material has come into question. And now there is an increased need for cholesterol of higher purity. Similarly as to cholesterol for use as materials for synthesis of pharmaceuticals or as reagents for biochemical research, the currently acceptable purity levels are now considered unsatisfactory. Consequently there is an increasingly strong demand for cholesterol of higher purity.
To improve the purity of cholesterol by conventional methods, repeated recrystallization is done. However, this way can not improve the purity and yield concurrently. For example, when recrystallization is repeated three times using a 95.5%-pure commercially available cholesterol as the starting cholesterol, the purity is increased to 98.8%, but the yield is markedly lowered to 42%. Thus this is not practical.
In view of such status of art, an object of the present invention is to provide a process for preparing cholesterol with a high purity in a high yield.
To achieve the above object, the inventors of the present invention assayed commercially available cholesterols (hereinafter "commercial cholesterol") by GLC and found that they had a purity of 90.7 to 96.3%. The commercial cholesterols were also found to contain 5.1 to 2.6% of desmosterol, as a main contaminant, having double bonds in the 5-position of the sterol skeleton and in the 24-position of the side chain. It was confirmed that the desmosterol can not be removed, except little by little, by recrystallization.
The inventors carried out further extensive investigations, directing attention to the desmosterol as a major contaminant, and found that the desmosterol is converted to cholesterol by the reduction of the double bond in the side chain of desmosterol. More specifically, the inventors found not only that the desmosterol can be converted to cholesterol but also that cholesterol can be obtained with a high purity and in a high yield by a selective reduction method substantially free of loss of cholesterol itself (loss due to the reduction). The present invention has been accomplished based on these novel findings.
DISCLOSURE OF THE INVENTION
According to the present invention, there is provided a process for preparing high-purity cholesterol, the process comprising selectively reducing the impurities contained in crude cholesterol to cholesterol.
Conventional hydrogenation catalysts can be used for the reduction in the invention. Examples of such catalysts are nickel, platinum, palladium, copper and like metal catalysts, Raney alloy catalyst
REFERENCES:
Patent Abstract of Japan--01-117897 A, May 10, 1989.
Patent Abstract of Japan--62-277396 A, Dec. 2, 1987.
J. of Lipid Research; vol. 20, No. 1, Jan. 1979; pp. 134-139; Bentzen C.L.
Journal of Organic chem., vol. 47, No. 9, 23 Apr. 1982, pp. 1722-1724; H. Kircher et al.--"Preparation of Some Unsaturated . . . ".
Journal of Organic Chem., vol. 52, No. 12; 12 Jun. 1987, pp. 2586-2588; H. Kircher et al.--"Preparation of Desmosterol from . . . ".
Progr. Biochem. Pharmacol.; vol. 5 (1969), pp. 24-34; Frantz I.D.; "Synthesis and use of labeled sterols". p. 29, paragraph 5.
Chemical Abstract, vol. 119, No. 6; 9 Aug. 1993, Abstract No. 51730 Lauko et al.; "Analysis of Steroids, Part 46 . . . ".
Chemical Abstract, vol. 76, No. 3; 17 Jan. 1972, Abstract No. 011352 Watkinson et al.; "Substrate activation in some pyridine nucleotide . . . ".
Journal of Chem. Soc., Chem. Commun., No. 10, 15 May 1991, Letchworth, GB pp. 688-689; Fujimoto, Y. et al.--"Stereochemistry of the hydrogen . . . ".
Journal of the American Chem. Society, vol. 95, No. 6; 21 Mar. 1973, DC; pp. 1996-2001; M.G. Kienle et al.--"Reduction of delta-24 Lanosterol . . . ".
Chem. Abs 105:94971 (1985).
Myojyo Katsunori
Osada Takeshi
Killos Paul J.
Nippon Fine Chemical Co., Ltd.
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