Unoprostone

Unoprostone

• Molecular FormulaC₂₂H₃₈O₅
• Average mass382.534 Da

Unoprostone (INN) is a prostaglandin analogue. Its isopropyl ester, unoprostone isopropyl, was marketed under the trade name Rescula for the management of open-angle glaucoma and ocular hypertension, but is now discontinued in the US.^[1]

Unoprostone isopropyl is a prostaglandin analogue. Ophthalmic Solution 0.15% is a synthetic docosanoid. Unoprostone isopropyl has the chemical name isopropyl (+)-(Z)-7-[(1R,2R,3R,5S)-3,5 dihydroxy-2-(3-oxodecyl)cyclopentyl]-5-heptenoate. The main indication of Unoprostane is treatment of glucoma.

This compound can be prepared by two different ways: 1) The reaction of 1-benzyl-4-(hydroxymethyl)pyrrolidin-2-one (I) with SOCl2 in refluxing dichloromethane gives 1-benzyl-4-(chloromethyl)pyrrolidin-2-one (II), which is condensed with potassium phthalimide (III) in DMF yielding 1-benzyl-4-(phthalimidomethyl)pyrrolidin-2-one (IV). Finally, this compound is treated with hydrazine in ethanol and neutralized with fumaric acid. 2) The dehydration of 1-benzyl-2-oxo-pyrrolidine-4-carboxamide (V) with POCl3 in hot DMF gives 1-benzyl-4-cyanopyrrolidine-2-one (VI), which is reduced with H2 and RaNi in methanol – NH3 and neutralized with fumaric acid. EP 0289349; JP 1989151552; US 5001153; US 5106869

syn 2

The condensation of dimethyl methylphosphonate (I) with ethyl octanoate (II) by means of butyllithium in THF gives dimethyl 2-oxononylphosphonate (III), which is condensed with the protected aldehyde (IV) by means of NaH in THF, yielding the unsaturated ketone (V). The hydrogenation of (V) with H2 over Pd/C in ethyl acetate affords the corresponding saturated ketone (VI), which is treated with ethylene glycol and p-toluenesulfonic acid to give the cyclic ketal (VII). The mild hydrolysis of (VII) with K2CO3 and acetic acid gives the alcohol derivative (VIII); the reduction of the lactone group of (VIII) with dibutylaluminum hydride in toluene affords the lactol (IX), which is condensed with (4-carboxybutyl)triphenylphosphonium bromide (X) by means of NaH in DMSO yielding the protected prostaglandin (XI). Esterification of (XI) with isopropyl iodide and DBU in acetonitrile gives the precursor (XII), which is finally deprotected with acetic acid in THF – water.

References

Unoprostone

Clinical data
Trade names	Rescula
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Topical (eye drops)
ATC code	S01EE02 (WHO)
Legal status
Legal status	US: Discontinued
Pharmacokinetic data
Elimination half-life	14 min
Excretion	Renal
Identifiers
IUPAC name[show]
CAS Number	120373-36-6  120373-24-2 (isopropyl ester)
PubChem CID	5311236
DrugBank	DB06826
ChemSpider	4470755
UNII	6X4F561V3W
KEGG	D08661
ChEMBL	ChEMBL1201407
ECHA InfoCard	100.227.145
Chemical and physical data
Formula	C22H38O5
Molar mass	382.534 g/mol g·mol−1
3D model (JSmol)	Interactive image
SMILES[hide] O=C(O)CCC/C=C\C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CCC(=O)CCCCCCC
InChI[hide] InChI=1S/C22H38O5/c1-2-3-4-5-8-11-17(23)14-15-19-18(20(24)16-21(19)25)12-9-6-7-10-13-22(26)27/h6,9,18-21,24-25H,2-5,7-8,10-16H2,1H3,(H,26,27)/b9-6-/t18-,19-,20+,21-/m1/s1  Key:TVHAZVBUYQMHBC-SNHXEXRGSA-N

///////////////Antiglaucoma, ocular hypertension, UF-021, Unoprostone

CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O

CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C