Ciloprost, Iloprost, E-1030, SH-401, ZK-36374, Ventavis, Endoprost, Ilom閐ine, Ilomedin

伊洛前列素Chemical Name: 5(E)-[(1S,5S,6R,7R)-7-Hydroxy-6-[(3S,4RS)-3-hydroxy-4-methyl-1(E)-octen-6-ynyl]bicyclo[3.3.0]octan-3-ylidene]pentanoic acid
CAS No. 73873-87-7
项目整合开发状态: Launched-1992
项目研究机构: CoTherix (Orphan Drug), Schering AG (Orphan Drug), Berlex (Originator), Schering AG (Originator), CoTherix (Licensee), Eisai (Licensee), Italfarmaco (Licensee)
合成路线:Reaction of the lactone (I) with lithium ethyl acetate followed by acid catalyzed dehydration and hydrolysis of the ester group with K2CO3 in methanol affords the hydroxy compound (II),which gives after Collins oxidation,treatment with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and reduction with NaBH4,the ketoester (III).Dealkoxy carbonylation with DABCO in toluene,benzoylation and removal of the silyl group with acetic acid in THF-water yield the ketone (IV).Ketalization of the ketone (IV) with ethylene glycol,Collins oxidation and condensation of the resulting aldehyde with the sodium salt of the phosphonate (V) afford the enone (VI).Reduction of (VI) with NaBH4 in methanol,cleavage of the ketal function with acetic acid-H2O and subsequent tetrahydropyranylation lead to the ketone (VII).Wittig condensation of the ketone (VII) with (VIII) and NaH in DMSO affords after chromatographic separation the acid (IX),which is finally deprotected to (X) (ZK-36374) by treatment with acetic acid in THF-water mixture.