新产品编号:1604657
Chemical Name: 15-O-[2-[4,4-Bis(phosphono)butylsulfanyl]acetyl]prostaglandin E2 disodium salt
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Tetraisopropyl methylenediphosphonate (I) was alkylated with 3-(acetylthio)propyl iodide (II) in the presence of NaH to give (III).Then,hydrolysis of both thioester and phosphonate esters of (III) with refluxing HCl provided the intermediate thiol (IV).
合成路线:Selective acylation of the silyl ester of prostaglandin E2 (V) at C-15 hydroxyl group with bromoacetyl bromide in the presence of pyridine at -25 C afforded bromoacetate ester (VI).Then,displacement of the halogen atom with thiol (IV) in aqueous dioxan furnished the correspondig desilylated sulfide.This was finally converted into the title disodium phosphonate salt by treatment with cation exchange resin.
📌 参考资料/链接：
参考文献标题:Prostaglandin conjugates for treating or preventing bone disease
文献作者:Gil,L.; Young,R.N.; Ruel,R.; Han,Y.(Merck Frosst Canada Inc.)
参考来源:US 6121253; WO 0031084
📄 详细内容
合成路线:Tetraisopropyl methylenediphosphonate (I) was alkylated with 3-(acetylthio)propyl iodide (II) in the presence of NaH to give (III).Then,hydrolysis of both thioester and phosphonate esters of (III) with refluxing HCl provided the intermediate thiol (IV).
合成路线:Selective acylation of the silyl ester of prostaglandin E2 (V) at C-15 hydroxyl group with bromoacetyl bromide in the presence of pyridine at -25 C afforded bromoacetate ester (VI).Then,displacement of the halogen atom with thiol (IV) in aqueous dioxan furnished the correspondig desilylated sulfide.This was finally converted into the title disodium phosphonate salt by treatment with cation exchange resin.
参考文献标题:Prostaglandin E2-bisphosphonate conjugates: Potential agents for treatment of osteoporosis
文献作者:Gil,L.; Han,Y.; Opas,E.E.; Rodan,G.A.; Ruel,R.; Seedor,J.G.; Tyler,P.C.; Young,R.N.
参考来源:Bioorg Med Chem 1999,7(5),901