Preparation of ursodeoxycholic acid by direct electro-reduction of 7-ketolithocholic acid

Xiangxi Yuan; Xiaolei Ma; Xuejun Cao

Korean Journal of Chemical Engineering, Vol.31, No.7, 1276-1280, July, 2014

DOI10.1007/s11814-013-0245-y Export Citation

Preparation of ursodeoxycholic acid by direct electro-reduction of 7-ketolithocholic acid

Xiangxi Yuan, Xiaolei Ma, and Xuejun Cao^†

State Key Laboratory of Bioreactor Engineering, Department of Bioengineering, East China University of Science & Technology, 130 Meilong Rd., Shanghai 200237, China

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A novel method of producing ursodeoxycholic acid was developed through direct electro-reduction of 7-ketolithocholic acid in a divided electrolytic cell. Titanium ruthenium mesh electrode was used as the anode, while high purity lead plate was used as the cathode. The process was optimized with regards to the electrolyte, temperature, concentration of methanol, current density and concentration of anolyte. When potassium bromide was used as the electrolyte, the saturated solution of 7-ketolithocholic acid in 85-93% (v/v) methanol, current density 9.52-28.6 A/m2 and concentration of anolyte at 4-6% (w/w), the maximum percentage yield of ursodeoxycholic acid could be 47%. The method will provide a potential approach for large-scale production of ursodeoxycholic acid.

Keywords:7-Ketolithocholic Acid;Chenodeoxycholic Acid;Ursodeoxycholic Acid;Direct Electroreduction;Potassium Bromide

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[1] Talwalkar JA, Lindor KD, Lancet, 362, 53 (2003)

[2] Hepatol J, European Association for the Study of the Liver, 51, 237 (2009)

[3] Salvioli G, Igimi H, Carey MC, J. Lipid. Res., 24, 701 (1983)

[4] Shiraki K, Ito T, Sugimoto K, Fuke H, Inoue T, Miyashita K, Yamanaka T, Suzuki M, Nabeshima K, Int. J. Mol. Med., 16, 729 (2005)

[5] Liu F, Cheng Y, Wu J, Tauschel HD, Duan RD, Cancer Lett., 235, 141 (2006)

[6] Galsky J, Bansky G, Holubova T, Konig J, J. Clin. Gastroenterol., 28, 249 (1999)

[7] Poupon RE, Lindor KD, Cauch DK, Dickson ER, Poupon R, Heathcote E, J. Gastroenterol., 113, 884 (1997)

[8] Santos VN, Lanzoni VP, Szejnfeld J, Shigueoka D, Parise ER, Braz. J. Med. Biol. Res., 36, 723 (2003)

[9] Shoda M, J. Biochem., 7, 505 (1927)

[10] Kanazawa T, Shimazaki A, Sato T, Hoshino T, Proc. Jpn. Acad., 30, 391 (1954)

[11] Claudio G, Francesco M, Mariano M, Giulio P, US Patent, 4,486,352 (1984)

[12] Kubota N, Mashita N, Japan Patent, 2,282,393 (1990)

[13] Hattori M, Mikami K, Sekine T, Japan Patent, 5,032,692 (1993)

[14] Bharucha R, Slemon E, US Patent, 4,547,271 (1985)

[15] Hatsutori, Japan Patent, 6,002,184 (1994)

[16] Terada M, Minami J, Abe N, Sato M, Horie Y, Komiyama M, Japan Patent, 60,217,899 (1985)

[17] Zhao HB, Tian H, Jin YH, Cao XJ, J. Appl. Electrochem., 40(7), 1307 (2010)