新产品编号:342221
Chemical Name: 2(R)-[N-Benzyl-N-[[R(P)]-(methyl)phenylphosphoryl]amino]-N-hydroxy-4-methylpentanehydroxamic acid; N2-Benzyl-N2-[[R(P)]-methyl(phenyl)phosphoryl]-N1-hydroxy-D-leucinamide
CAS No. 204274-80-6
项目整合开发状态: Biological Testing
项目研究机构: Procter & Gamble (Originator)
合成路线:The esterification of D-leucine (I) with benzyl alcohol and HCl gives the corresponding ester (II),which is N-benzylated by reductocondensation with benzaldehyde and sodium cyanoborohydride yielding N-benzyl-D-leucine benzyl ester (III).The condensation of (III) with methyl phenyl phosphinyl chloride (IV) by means of N-methylmorpholine in dichloromethane affords the phosphinylamino derivative (V),which is treated with H2 over Pd/C in methanol to give N-benzyl-N-[methyl(phenyl)phosphinyl]-D-leucine (VI).The condensation of (VI) with O-benzylhydroxylamine (VII) by means of 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide (DEC) and HOBT in DMF yields the N-benzyl hydroxamic acid (VIII) as a diastereomeric mixture that is separated by flash chromatography providing the diastereomer (IX).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.
📌 参考资料/链接：
参考文献标题:Phosphinic acid amides as matrix metalloprotease inhibitors
文献作者:Taiwo,Y.O.; Pikul,S.; De,B.; McDow-Dunham,K.L.(The Procter & Gamble Co.)
参考来源:US 5830915; WO 9808853
📄 详细内容
合成路线:The esterification of D-leucine (I) with benzyl alcohol and HCl gives the corresponding ester (II),which is N-benzylated by reductocondensation with benzaldehyde and sodium cyanoborohydride yielding N-benzyl-D-leucine benzyl ester (III).The condensation of (III) with methyl phenyl phosphinyl chloride (IV) by means of N-methylmorpholine in dichloromethane affords the phosphinylamino derivative (V),which is treated with H2 over Pd/C in methanol to give N-benzyl-N-[methyl(phenyl)phosphinyl]-D-leucine (VI).The condensation of (VI) with O-benzylhydroxylamine (VII) by means of 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide (DEC) and HOBT in DMF yields the N-benzyl hydroxamic acid (VIII) as a diastereomeric mixture that is separated by flash chromatography providing the diastereomer (IX).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.
参考文献标题:A multinuclear MR study of Gd-EOB-DTPA: Comprehensive preclinical characterization of an organ specific MRI contrast agent
文献作者:Elst,L.V.; Maton,F.; Laurent,S.; Seghi,F.; Chapelle,F.; Muller,R.N.
参考来源:Magn Reson Med 1997,38(4),604