Methyl cholate

Methyl Cholate is methyl ester form of Cholic acid. Cholic acid is one of the major bile acids produced by the liver, where it is synthesized from cholesterol[1].

To a solution of compound 1 (2.0 g, 4.9 mmol) in PhCHCompound 47: A solution of acetyl chloride (0.125 mL) in 125 mL of methanol was treated with cholic acid (5 g, 0.012 mol) in one portion. The solution was stirred at room temperature for 72 h, at which time the solvent was concentrated in vacuo to give compound 47 (5.0 g, quantitative) as white solid: m/z 423.2 (M+l).A mixture of cholic acid (2.01 g, 4.9 mmol) and p-toluenesulphonyl acid monohydrate (500 mg, 2.63 mmol) in methanol (50 ml) was irradiated by MW for 6 min at 50percent of maximum intensity (i.e. at 375 W). After evaporation of methanol, water was slowly added until the product starts to crystallize, and the crude product was filtered and washed with water. Recrystallization from methanol-water yielded 2.07 g (99percent) of methyl cholatecholate, m.p 107°C-109 °C. Literature [15] gives different value of m.p, 156-157 °C.[0052] To a solution of cholic acid (0.3 g, 0.74 mmol) in dry methanol (10 mL)was added p-TSA (0.03 g, 0.17 mmol). The mixture was stirred at 28°C for 24 hrs.Methanol was evaporated and the residue was extracted with CH2Ch (3x50 mL). Theorganic extract was washed with cold H20 (2x10 mL), 10percent NaHC03 (2x10 mL), brine (2x 10 mL) and dried over Na2S04. Solvent was evaporated under reduced15 pressure to afford crude product. Purification by column chromatography on silica gel(5 percent, MeOH/CHCh) afforded compound methyl 3a., 7a, 12a-trihydroxy-5J3-cholane-24-oate. (0.3 g, 98 percent) as a white solid. mp 155-156 oc; [a]028+ 31.33 (CHCh, c 1.0);IR (cm-1): 3376, 1731; 1H NMR (CDCh, 200 MHz): 8 0.68 (s, 3H, CH3-18), 0.89 (s, 3H, CH3-19), 0.98 (d, J = 5.7 Hz, 3H, CH3-21), 3.57 (m, 1H CH-3), 3.67 (s, 3H)20 3.89 (bs, 1H, CH-7), 4.01 (bs, 1H, CH-12); 13C NMR (CDCh, 50 MHz): 8 12.8, 17.7, 22.8, 23.6, 26.6, 27.7, 28.5, 30.0, 31.4, 31.5, 35.2, 35.2, 35.7, 35.8, 39.9, 39.9, 42.0, 42.0, 46.8, 47.3, 51.8, 68.8, 72.2, 73.4, 175.2.General procedure: Bile acids (5–8) (2.65 mmol)were dissolved in anhydrousmethanol(40 mL), and conc. hydrochloric acid (1 mL) was added. Reaction mixturewasstirred for 12 h at roomtemperature. After completion of reaction, solvent was evaporated under vacuum and reaction mixture wasdiluted with ethyl acetate (50 mL). Reaction mixture was washedwith sodiumbicarbonate (2 × 10 mL) and brine (2 × 5 mL). Organicphase was dried over sodium sulfate and concentrated in vacuum toobtain pure product.Protection of cholic acid (1) afforded the methyl ester (2) that was oxidized withJV-bromosuccinimide (NBS) to the corresponding ketone (3). This compound was then protected as the diacetate (4) and converted to the key intermediate (5) on reaction with molecular bromine. This bromide was then hydrolyzed to the hydroxyl-ketone (6). Subsequent reduction and global deprotection of the acetate and methyl ester moieties afforded the target compound (7).General procedure: The mixture of carboxylic acid, alcohol and N-bromosuccinimide was stirred in a 25 mL reactortube at 70 °C for 2–40 h. After the completion of the reaction, the mixture was cooled to roomtemperature and alcohol was evaporated under reduced pressure. The isolation procedure was as follows, except where noted differently in Section 3.2.6. The residue was dissolved in ethyl acetate andconsecutively washed with 10 mL of 10percent Na2S2O3 (aq), 5 mL of saturated NaHCO3 (aq) and 10 mL ofdistilled water. The water phase was extracted with ethyl acetate (3Χ5 mL). The organic layers were combined, dried over Na2SO4 and the solvent was evaporated under reduced pressure.Cholic acid (5.0 g, 12.2 mmol) was added to dry methanol (20 mL). Acetylchloride (0.5 mL, 0.04 mmol) was added under argon. The solution was heated at reflux for 45 minutes, then left to cool. Once at room temperature, the solution was cooled further on ice whereupon crystals appeared. The solid material was collected by filtration and washed with small amounts of methanol to give methyl cholate as a white solid. It was dried at room temperature under vacuum. Yield= 3.548g (68.9percent) Melting point= 110.8- 111.9 °C lH NMR (CDC1Take 10 g of raw acid cholic acid dissolved in 30 ml of methanol, add 1 ml of concentrated hydrochloric acid, and reflux for 1 h.The mixture was slowly cooled to room temperature, crystals were precipitated, suction filtered, and dried in vacuo to give 10.25 g of white crystals.

Protected Cholic Acid

Molecular Weight:422.6
XLogP3:3.9
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:5
Exact Mass:422.30322444
Monoisotopic Mass:422.30322444
Topological Polar Surface Area:87
Heavy Atom Count:30
Complexity:652
Undefined Atom Stereocenter Count:11
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes