Latanoprost CAS NO.130209-82-4

Xalatan was launched in Sweden, Switzerland and the US for the treatment of glaucoma. It can be synthesized, from the Corey lactone, using standard prostaglandin chemistry. Latanoprost is a PGF_2α, analog that is more lipophilic thus is better able to penetrate the cornea. The (15R)-diastereomer has only 10% of the activity compared to the (15S)-diastereomer. It is a selective FP receptor agonist with little or no effect on the other prostanoid receptors. The antiglaucoma effects are the result of reduced intraocular pressure arising by increasing uveoscleral outflow with little or no effect on trabeculo-canalicular aqueous outflow and no effect on retinal vasculation or permeability of the blood-aqueous barrier. The topical application is sufficient for a single daily dosage and is well tolerated with no detectible conjunctival hyperaemia.

Manufacturing process for Latanoprost includes these steps as follows: Synthesis of [3aR-[3aα,4α(E),5β,6aα]]-5-(benzoyloxy) hexahydro-4-(3-oxo-5-phenyl-1-pentenyl)-2H-cyclopenta[b]furan-2-one, synthesis of [3aR-[3aα,4a(1E,3S),5β,6aα]]-5-(benzoyloxy)hexahydro- 4-(3 -hydroxy-5-phenyl-1-pentenyl)-2H-cyclopenta[b]furan-2-one, synthesis of [3aR-[3aα,4a(1E,3S),5β,6aα]]- 5-(benzoyloxy)hexahydro-4-(3-hydroxy-5-phenyl-1-pentyl)-2Hcyclopenta[b]furan-2-one, synthesis of 2-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5- phenylpentyl]cyclopentyl]acetic acid, synthesis of [3aR-[3aα,4α(R),5β,6aα]]-hexahydro-5-hydroxy-4-(3-hydroxy-5- phenylpentyl)-2H-cyclopenta[b]furan-2-one, synthesis of [3aR-[3aα,4α(R),5β,6aα]]- hexahydro-5-hydroxy-4-(3-hydroxy-5-phenylpentyl)-2H-cyclopenta[b]furan-2-one;synthesis of (3aR,4R,5R,6aS)-5- (1-ethoxyethoxy)-4-[(3R)-3-(1-ethoxyethoxy)-5-phenylpentyl]hexahydro-2Hcyclopenta[b]furan-2-ol;synthesis of 7-[(1R,2R,3R,5S)-3-(1-ethoxyethoxy)-5- hydroxy-2-[(3R)-3-(1-ethoxyethoxy)-5- phenylpentyl]cyclopentyl-5-heptenoic acid; synthesis of (5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5- phenylpentyl]cyclopentyl]-5-heptenoic acid (Latanoprost Acid); At last, Latanoprost acid is dissolved in DMF (10 mL) and added to a slurry of cesium carbonate (1.6 g) in DMF (10 mL). 2-Iodopropane (0.49 mL) is added and the slurry is heated to 45°C for about 6 hours. When the reaction is complete, MTBE (40 mL) and water (50 mL) are added and the mixture is stirred for 15 min. The phases are separated and the aqueous phase is washed with MTBE (20 mL). The organic phases are combined and concentrated. The concentrate is chromatographed (silica gel) eluting with MTBE. The appropriate fractions are pooled and concentrated to give (5Z)-(9CI)-7-[(1R,2R,3R,5S)-3,5- Dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl ]cyclopentyl]-5-heptenoic acid 1- methylethyl ester (Latanoprost).