Description
Deoxycholic acid
sodium salt, which is a secondary bile acid and the metabolite
of intestinal bacteria, provides a nonsurgical treatment to
significantly reduce submental fat in adults via injection directly
into moderate-to-severe fatty tissue below the neck. When
injected into fatty tissue, deoxycholic acid helps destroy fat
cells. Although deoxycholic acid has many applications
beyond human health, the application as a dyslipidemia drug
was licensed to Kythera from Los Angeles Biomedical Institute
at Harbor-UCLA Medical Center in 2007. Allergan acquired
Kythera recently in 2015.
Chemical Properties
white powder
Uses
A Cholic Acid (C432600) derivative used as a component in cell lysis buffers.
Uses
antiinflammatory, immunomodulator, antineoplastic
Definition
ChEBI: Deoxycholic acid is a bile acid that is 5beta-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 12 respectively. It has a role as a human blood serum metabolite. It is a bile acid, a dihydroxy-5beta-cholanic acid and a C24-steroid. It is a conjugate acid of a deoxycholate.
General Description
This [TM="Certified Spiking Solution" is suitable for use as starting material in the preparation of linearity standards, calibrators, and controls in LC-MS/MS and GC/MS bile acid testing methods. Deoxycholic acid (DCA), also known as deoxycholate and cholanoic acid is a secondary bile acid that aids in the absorption of fats in the intestine. Mass spectrometry-based analysis of DCA is routinely performed in clinical diagnostic testing applications including neonatal testing of inborn errors of bile acid synthesis and differentiating among types of familial intrahepatic cholestasis.
Biochem/physiol Actions
Deoxycholic acid, due to its amphiphilicity, significantly helps to solubilize, emulsify, and absorb fat, vitamins, and cholesterol in the body. High levels of intestinal deoxycholic acid might cause colorectal cancer by inducing oxidative stress and leading to DNA damage. It acts as an oncogene and pro-tumor factor.
Synthesis
The synthesis started from the commercially available 9-
hydroxyandrost-4-ene-3,17-dione (114).85 Hydrogenation
of 114 gave the saturated 5|?-dione 115 in 85% yield.
Alcohol 115 was then dehydrated with H2SO4 in CH2Cl2 to
provide 5|?-androst-9(11)-ene-3,17-dione 116 in 95% yield as
off-white solid, and this was followed by selective reduction
with LiAlH(O-t-Bu)3 to afford (3|á,5|?)-3-hydroxyandrost-
9(11)-en-17-one (117). The crude ketone 117 was submitted
to a Wittig reaction with triphenylethylphosphonium bromide
in the presence of potassium t-butoxide in THF to yield
(3|á,5|?,17E)-pregna-9(11),17-dien-3-ol (118). The crude alcohol
118 was acetylated with Ac2O in the presence of DMAP
and Et3N to yield prenyl acetate 119 in 64% across the threestep
sequence. Compound 119 was reacted with methyl
acrylate in the presence of EtAlCl2 to facilitate conjugate
addition and subsequent tertiary carbocation elimination to
afford adduct 120, and this resulting olefin was hydrogenated to
selectively saturate the cyclopentenyl double bond, resulting in
steroid 121 in 85% yield from 119. The remaining alkene 121
then underwent allylic oxidation with tert-butyl hydrogen
peroxide and 10% NaOCl aqueous solution in EtOAc to give
enone 122, and this material was then hydrogenated over 10%
Pd/C in EtOAc to afford the saturated ketone 123. Next, the
ketone within 123 was selectively reduced with LiAlH(O-t-Bu)3
in THF to give the 12|á-hydroxy precursor 124 in excellent
yield. Finally the remaining methyl ester 124 was hydrolyzed
with 20% NaOH aqueous solution in THF/MeOH and
acidified with 4 M HCl to give deoxycholic acid (XV) in
99% yield as a white solid.
Purification Methods
Reflux the acid with CCl4 (50mL/g), filter, evaporate under vacuum at 25o, recrystallise the residue from acetone and dry it under vacuum at 155o [Trenner et al. J Am Chem Soc 76 1196 1954]. A solution of (cholic acid-free) material (100mL) in 500mL of hot EtOH is filtered, evaporate it to less than 500mL on a hot plate, and pour it into 1500mL of cold diethyl ether. The precipitate, filtered off by suction, is crystallised twice from 1-2 parts of absolute EtOH, to give an alcoholate, m 118-120o, which is dissolved in EtOH (100mL for 60g) and poured into boiling water. After boiling until free of the EtOH, the precipitate is filtered off, dried, ground and dried to constant weight in vacuo [Sobotka & Goldberg Biochem J 26 555 1932]. Deoxycholic acid is also freed from fatty acids and cholic acid by silica gel chromatography and elution with 0.5% acetic acid in ethyl acetate [Tang et al. J Am Chem Soc 107 4058 1985]. It can also be recrystallised from butanone. Its solubility in H2O at 15o is 0.24g/L, but in EtOH it is 22.07g/L. [Beilstein 10 IV 1608.]
