(11α)-16,16-Difluoro-11-hydroxy-9,15-dioxoprostan-1-oic acid

Lubiprostone(SPI-0211;RU0211) is a gastrointestinal agent used for the treatment of idiopathic chronic constipation.Target: OthersLubiprostone is a bicyclic fatty acid derived from prostaglandin E1 that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). From Wikipedia.

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RU-0211 is a prostanoid.|Lubiprostone is an activator of chloride channels (ClC-2) in the intestine and is used for treatment of chronic constipation and irritable bowel syndrome. Lubiprostone has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.|Member of a bicyclic fatty acid class of compounds derived from PROSTAGLANDIN E1 involved in chloride channel gating.

To a solution of(Z)-7-[(1 R, 2R, 3R)-2-((E)-4, 4-difluoro-3-oxo-1 -octenyl)-3-(phenylmethoxy)-5-ox ocyclopentyl]-5-heptenoic acid (10, RTo a solution of(Z)-7-[(1 R, 2R, 3R)-2-((E)-4, 4-difluoro-3-oxo-1 -octenyl)-3-(phenylmethoxy)-5-ox ocyclopentyl]-5-heptenoic acid (10, RPreparation of Crude Lubiprostone (0090) 4-Methoxybenzyl 7-[ (2R, 4aR, 5R, 7aR)-2-(1, 1-difluoro-pentyl)-octahydro-2-hydroxy-6-oxocyclopenta[b]pyran-5-yl)heptanoate (60 g, 117.5 mmol, enantiomeric purity '99%) was dissolved in 600 ml ethyl acetate and followed by addition of 5% palladium on charcoal under hydrogen for 3 hours. Then, the reaction mixture was filtered with celite pad. The solvent was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent to obtain 40 g oily Lubiprostone. HPLC analysis of the product showed that 1.1% impurity A was found.To a solution of compound 10 (150 g) in dichloromethane (15 volumes), was added 10% palladium on carbon (35% wt) and the suspension was hydrogenated at 2 PSI for 15 hours. After the completion of the reaction, the mixture was filtered through Celite, concentrated to near dryness and purified by column chromatography (ethyl acetate in hexanes) to give crude Lubiprostone. To a solution of crude Lubiprostone in ethyl acetate (10 vol) was added tert-butylamine (1.05 eq) at room temperature. The mixture was stirred at room temperature until precipitation of the amine salt occurred. The amine salt was isolated by filtration and dried to give Lubiprostone tert- butylamine salt (20 g). The amine salt was suspended in ethyl acetate (6 volumes) and water (3 volumes). The resulting bi-phasic mixture was adjusted to about pH 5 with formic acid. The organic layer was separated and concentrated to obtain Lubiprostone as a syrup. Upon crystallization using ethyl acetate/petroleum ether (1 :9 volumes), the syrup produced Lubiprostone(1 , 12 g) in approximately 70% recovery. The Lubiprostone filtrate was concentrated to near-dryness. HRMS (ESI+) [M + NH4]+ of (1): Formula: C20H36F2NO5: cal m/z: 408.25561 amu, found: 408.25626 amu .To a solution of compound 10 (150 g) in dichloromethane (15 volumes), was added 10% palladium on carbon (35% wt) and the suspension was hydrogenated at 2 PSI for 15 hours. After the completion of the reaction, the mixture was filtered through Celite, concentrated to near dryness and purified by column chromatography (ethyl acetate in hexanes) to give crude Lubiprostone. To a solution of crude Lubiprostone in ethyl acetate (10 vol) was added tert-butylamine (1.05 eq) at room temperature. The mixture was stirred at room temperature until precipitation of the amine salt occurred. The amine salt was isolated by filtration and dried to give Lubiprostone tert- butylamine salt (20 g). The amine salt was suspended in ethyl acetate (6 volumes) and water (3 volumes). The resulting bi-phasic mixture was adjusted to about pH 5 with formic acid. The organic layer was separated and concentrated to obtain Lubiprostone as a syrup. Upon crystallization using ethyl acetate/petroleum ether (1 :9 volumes), the syrup produced Lubiprostone(1 , 12 g) in approximately 70% recovery. The Lubiprostone filtrate was concentrated to near-dryness. HRMS (ESI+) [M + NH4]+ of (1): Formula: C20H36F2NO5: cal m/z: 408.25561 amu, found: 408.25626 amu .

Lubiprostone is a bicyclic fatty acid metabolite analog of Prostaglandin E1.It activates specific chloride channels in the gastrointestinal tract to stimulate intestinal fluid secretion, increase gastrointestinal transit, and improve symptoms of constipation.

Molecular Weight:390.5
XLogP3:4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:11
Exact Mass:390.22178044
Monoisotopic Mass:390.22178044
Topological Polar Surface Area:83.8
Heavy Atom Count:27
Complexity:525
Defined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes