Description
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 PGF2α, 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
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).
General Description
Latanoprost (Xalatan) is available as a 0.005% sterileophthalmic solution in a 2.5-mL dispenser bottle.Latanoprost is also marketed as a combination ophthalmicproduct with the β-adrenergic blocking agent, timolol,which apparently enhances IOP-lowering by decreasing theproduction of aqueous humor. Cautions and side effects aresimilar to those for other ophthalmic prostanoids.
Biochem/physiol Actions
Latanoprost is a potent, selective prostaglandin F2α?analog receptor agonist. It is hydrolyzed by esterases into its biologically active form latanoprost acid in the cornea. Latanoprostplays a role in reducing the intraocular pressure (IOP) due to which it has therapeutic effects in treating glaucoma.
