Marimastat, TA-2516, BB-2516

马立马司他Chemical Name: N1-[2,2-Dimethyl-1(S)-(N-methylcarbamoyl)propyl]-N4,3(S)-dihydroxy-2(R)-isobutylsuccinamide; 3(R)-[N-[2,2-Dimethyl-1(S)-(N-methylcarbamoyl)propyl]carbamoyl]-2(S)-hydroxy-5-methylhexanohydroxamic acid; N2-[3(S)-Hydroxy-4-(N-hydroxyamino)-2(R)-isobutylsuccinyl]-N1-methyl-L-tert-leucinamide
CAS No. 154039-60-8
项目整合开发状态: Discontinued
项目研究机构: Vernalis (Originator), Schering-Plough (Licensee), Tanabe Seiyaku (Licensee)
合成路线:Treatment of butanedioate derivative (I) with methallyl iodide (II) and LDA in THF affords alkene (III),which is then reduced by hydrogenation over Pd/C and subjected to saponification by means of KOH in dioxane to yield succinic acid (IV).Protection of (IV) with 2,2-dimethoxypropane (V) and p-TsOH in DMF provides derivative (VI),which is then coupled with pentafluorophenol (VII) by using EDC in CH2Cl2 to furnish activated ester (VIII).Displacement of the pentafluorophenol moiety of (VIII) by treatment with L-tert-leucine methylamide (IX) in DMF gives methylamide derivative (X),which is deprotected with THF and HCl and condensed with O-benzylhydroxylamine (XI) by means of EDC to afford derivative (XII).Finally,(XII) is debenzylated by hydrogenation over Pd/C in EtOH to give the target compound.