新产品编号:1403743
Chemical Name: (1S,2S,4S)-N-[1,4-Dibenzyl-2-hydroxy-4-[2-(2-pyridinylmethoxycarboxamido)benzamido]butyl]carbamic acid thiazol-5-ylmethyl ester
项目整合开发状态: Preclinical
项目研究机构: National Cancer Institute (Originator)
合成路线:The reaction of L-phenylalanine (I) with benzyl chloride and K2CO3 gives the tribenzylated compound (II),which is condensed with acetonitrile by means of NaNH2 yielding 4(S)-(dibenzylamino)-3-oxo-4-phenylbutyronitrile (III).The reaction of (III) with benzylmagnesium chloride in THF affords the unsaturated,partially protected diaminohexenone (IV),which is reduced with NaBH4 and NaBH3(OTf) to provide a mixture of diastereomeric diaminohexanones,from which the desired diastereomer (V) is isolated by crystallization.The acylation of the free amino group of (V) with acylated anthranilic acid (VI) by means of HOBT gives the expected amide (VII),which is debenzylated by treatment with Pd/C and ammonium formate yielding intermediate (VIII).Finally this compound is acylated with the activated N-succinylcarbamate (IX) to afford the desired target compound.
📌 参考资料/链接：
参考文献标题:Unsymmetric nonpeptidic HIV protease inhibitors containing anthranilamide as a P2' ligand
文献作者:Randad,R.S.; Lubkowska,L.; Eissenstat,M.A.; Gulnik,S.V.; Yu,B.; Bhat,T.N.; Clanton,D.J.; House,T.; Stinson,S.F.; Erickson,J.W.
参考来源:Bioorg Med Chem Lett 1998,8(24),3537
📄 详细内容
合成路线:The reaction of L-phenylalanine (I) with benzyl chloride and K2CO3 gives the tribenzylated compound (II),which is condensed with acetonitrile by means of NaNH2 yielding 4(S)-(dibenzylamino)-3-oxo-4-phenylbutyronitrile (III).The reaction of (III) with benzylmagnesium chloride in THF affords the unsaturated,partially protected diaminohexenone (IV),which is reduced with NaBH4 and NaBH3(OTf) to provide a mixture of diastereomeric diaminohexanones,from which the desired diastereomer (V) is isolated by crystallization.The acylation of the free amino group of (V) with acylated anthranilic acid (VI) by means of HOBT gives the expected amide (VII),which is debenzylated by treatment with Pd/C and ammonium formate yielding intermediate (VIII).Finally this compound is acylated with the activated N-succinylcarbamate (IX) to afford the desired target compound.
参考文献标题:An efficient stereocontrolled strategy for the synthesis of hydroxyethylene dipeptide isosteres
文献作者:Stuk,T.L.; et al.
参考来源:J Org Chem 1994,59(15),4040