Sulprostone, ZK-57671, SH-B-286, CP-34089, Nalador

硫前列酮Chemical Name: 16-Phenoxy-omega-17,18,19,20-tetranor-PGE2 methylsulfonamide
CAS No. 60325-46-4
项目整合开发状态: Launched-1981
项目研究机构: Schering AG (Originator)
合成路线:The condensation of methyl phenoxyacetate (I) with dimethyl methylphosphonate (II) by means of butyllithium in THF gives dimethyl 2-oxo-3-phenoxypropylphosphanate (III),which by a Wittig condensation with 2-[3alpha-(p-phenylbenzoyloxy)-5alpha-hydroxy-2beta-formylcyclopentan-1alpha-yl]acetic acid gamma-lactone (IV) by means of butyllithium in hexane yields the keto lactone (V).This compound is reduced with zinc borohydride in dimethoxyethane affording the hydroxylactone (VI),which is hydrolyzed with K2CO3 in methanol giving the dihydroxylactone (VII).The hydroxyl groups of (VII) are protected with dihydropyrane as usual giving (VIII),which is reduced with diisobutylaluminitim hydride in toluene yielding the hemiacetal (IX).

合成路线:A Wittig condensation of [4-(methanesulfonylaminocarbonyl)butyl]triphenylphosphonium bromide (X) [the phosphonium bromide (X) is prepared bv reaction of 5-bromovaleryl chloride (Xl) with methanesulfonamide (XII) at 100 C to give N-methanesulfonyl-5-bromovaleramide (XIII),which is then condensed with triphenylphosphine in refluxing acetonitrile] with hemiacetal (IX) by means of Na in DMSO affords N-methanesulfonyl-9alpha-hydroxy-11alpha,15alpha-bis(tetrahydropyranyloxy)-16-phenoxy-5-cis-13-trans-omega-tetranorprostadienamide (XIV),which is then oxidized with the Jones reagent in acetone to the keto compound (XV).Finally,this compound is deprotected with acetic acid.