Urolithin A

Urolithin A is an intestinal metabolite of ellagic acid with antioxidant and antiproliferative effects; inhibits T24 and Caco-2 cell growth with IC50 values of 43.9 and 49 μM, respectively.

Solid

Urolithin A is a member of coumarins. It has a role as a geroprotector.|Urolithin A is a metabolite of ellagic acid. It has been demonstrated to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging.

Step 2: Ether Cleavage Batch RRO1L111AO. The reactor was charged with 8-methyl urolithin A (i5.25 kg, 63.0 mol), 5.0 equiv. of aluminum chloride (42.0 kg, 3i5.0 mol) and iO.3 vol. of toluene(i37.0 kg, i57 L). Agitation was started and the reaction mixture was heated to 90 °C within 75 mi Stirring was continued for 2 hours at 90-96 °C. After cooling the reaction mass to 53 °C over 25 mm., 0.6 vol. of water for injection (9.4 L) followed by iO.8 vol. of purified water (i64 L) were added within 2 hours carefully at 48-53 °C. Agitation wascontinued for 2 hours at 39-48 °C to remove all tipping from the reactor wall before the mixture was cooled to 37 °C in i5 mm. The product was collected by filtration at 23-37 °C (70 mm required) and the filter cake was rinsed with 4.2 vol. of methanol (50.0 kg, 63 L, 30 mm required). After combination of the mother liquor with the rinse solution the mixture was checked for residual product and discarded. The filter cake was dried in a flow of drynitrogen at ambient temperature for 2 hrs. until LOD = 65 percentwt.The crude product urolithin A was received in a yield of 46.6 kg and was used in batch RRO3Li i iAO as it was.Batch RRO2L111AO. The reactor was charged with 8-methyl urolithin A (i5.25 kg, 63.0 mol), 5.0 equiv. of aluminum chloride (42.0 kg, 3i5.0 mol) and iO.3 vol. of toluene(i37.0 kg, i57 L). Agitation was started and the reaction mixture was heated to 90 °C within 72 mm. Stirring was continued for 2 hours at 90-96 °C. After cooling the reaction mass to 58 °C over 30 mm, 0.7 vol. of water for injection (iO.2 L) followed by iO.5 vol. of purified water (160 L) were added within 2 hours carefully at 51-58 °C. Agitation was continued for 2 hours at 39-51 °C to remove all tipping from the reactor wall before the mixture was cooled to 37 °C in 5 mm. The product was collected by filtration at 30-37 °C (35 mm required) and the filter cake was rinsed with 4.2 vol. of methanol (50.0 kg, 63 L, 20mm required). After combination of the mother liquor with the rinse solution the mixture was checked for residual product and discarded. The filter cake was dried in a flow of dry nitrogen at ambient temperature for 2 hrs. until LOD = 55 percentwt.The crude product urolithin A was received in a yield of 43.8 kg and was used in batch RRO3L1 1 lAO as it was.Batch RRO3L111AO. The reactor was charged with urolithin A from previous batches RRO1L111AO (45.6 kg (LOD: 65 percentwt.)), RRO2L111AO (43.3 kg (LOD: 55 percentwt.)) and 4.1 vol. of DMSO (139 kg, 126 L). Agitation was started and stirring was continued until a clear solution was obtained at 20-25 °C (1.5 hours). A second reactor was charged with 12.1 vol. of purified water (370 L) and agitation was initiated. The DMSO-solutionwas added through a particle filter over 65 mm at 20-24 °C. The line (ist reactor, particle filter, 2’ reactor) was rinsed with 0.3 vol. of DMSO (10 kg, 9 L) and the rinse solution was combined with the suspension in the second reactor. Stirring of the suspension was continued for 35 mm at 23 °C. The raw product was collected by filtration at ambient temperature (7 days required) and the filter cake was rinsed with 4.1 vol. of purified water(125 L, 3.5 days required). After combination of the mother liquor with the rinse solution the mixture was checked for residual product and disposed. The filter cake was dried in a flow of dry nitrogen at ambient temperature for 7 hours until LOD = 86-89 percentwt. Drying of the filter cake was continued under reduced pressure for 18 hours at max. 60 °C until LOD = 8 1-86 percentwt.The raw product urolithin A was obtained in a yield of 25.2 kg and was used in batch RRO3L1 1 1A1 as it was.Batch RRO3L111A1. The reactor was charged with urolithin A from previous batch RRO3L111AO (25.2 kg) and 8.2 vol. of particle free acetic acid (264 kg, 251 L). Agitation was started and the slurry was heated to reflux within 65 mi Reflux was continued for 5hours before cooling to 41 °C within 50 mm. The solid was collected by filtration at 20-26°C (25 hours required) and the filter cake was rinsed subsequently with 4.1 vol. of particle free acetic acid (132 kg, 126 L, 21 hours required) and 4.1 vol. of particle free TBME (93kg, 126 L, 16 hours required). After combination of the mother liquor with the rinse solution the mixture was checked for residual product and discarded. The filter cake was dried under reduced pressure at 80 °C for 21 hours. The damp product was delumped and drying was continued under reduced pressure for 33 hours at 20-80 °C.The product urolithin A was obtained in 24.1 kg corresponding to an overall yield of84 percent for the ether cleavage and 96 percent recovery for the re-processing.General procedure: A solution of methyl ether of urolithins A–C 30a–c (1.0equiv) was cooled at 0°C under Ar atmosphere and was added BBr

Molecular Weight:228.20
XLogP3:2.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:228.04225873
Monoisotopic Mass:228.04225873
Topological Polar Surface Area:66.8
Heavy Atom Count:17
Complexity:317
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes