合成路线:Treatment of alanine (I) with phosgene in THF provides N-carboxyanhydride derivative (II),which is then coupled to proline (III) by means of KOH and K2CO3 in THF/H2O or acetonitrile to provide dipeptide (IV).Coupling of (IV) to ethyl 2-oxo-4-phenylbutyrate (V) by means of H2 over Raney-Ni in EtOH (or EtOH/HOAc),followed by the corresponding work-up for isomer separation,yields derivative (VI).(In turn,ketoester (V) can be obtained by treatment of 2-phenylethyl bromide (VII) with Mg turnings in refluxing THF,followed by reaction of the resulting Grignard reagent with diethyl oxalate (VIII) in THF).Finally,the desired product is obtained by saponification of the ethyl ester group of (VI) with NaOH.
参考文献标题:Improved stereoselective process for enalapril
文献作者:Reider,P.J.; Huffman,M.A.; Leblond,C.; Sun,Y.(Merck & Co.,Inc.)
参考来源:WO 0017228
合成路线:by reductocondensation of 4-phenyl-2-oxo butyric acid (IX) with L-alanyl-L-proline (IV) by means of sodium cyanoborohydride and NaOH in water.
参考文献标题:Amino acid derivs.as antihypertensives
文献作者:Tristram,E.W.; Patchett,A.A.; Harris,E.E.; Wyvratt,M.J.(Merck & Co.,Inc.)
参考来源:US 4472380
合成路线:by reductocondensation of 4-phenyl-2-oxo butyric acid (IX) with L-alanyl-L-proline (IV) by means of sodium cyanoborohydride and NaOH in water.
参考文献标题:Enalaprilat
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1986,11(8),647
合成路线:Treatment of alanine (I) with phosgene in THF provides N-carboxyanhydride derivative (II),which is then coupled to proline (III) by means of KOH and K2CO3 in THF/H2O or acetonitrile to provide dipeptide (IV).Coupling of (IV) to ethyl 2-oxo-4-phenylbutyrate (V) by means of H2 over Raney-Ni in EtOH (or EtOH/HOAc),followed by the corresponding work-up for isomer separation,yields derivative (VI).(In turn,ketoester (V) can be obtained by treatment of 2-phenylethyl bromide (VII) with Mg turnings in refluxing THF,followed by reaction of the resulting Grignard reagent with diethyl oxalate (VIII) in THF).Finally,the desired product is obtained by saponification of the ethyl ester group of (VI) with NaOH.
参考文献标题:Process for preparing polypeptides
文献作者:Blacklock,T.J.; Shuman,R.F.(Merck & Co.,Inc.)
参考来源:US 4510083
合成路线:Treatment of alanine (I) with phosgene in THF provides N-carboxyanhydride derivative (II),which is then coupled to proline (III) by means of KOH and K2CO3 in THF/H2O or acetonitrile to provide dipeptide (IV).Coupling of (IV) to ethyl 2-oxo-4-phenylbutyrate (V) by means of H2 over Raney-Ni in EtOH (or EtOH/HOAc),followed by the corresponding work-up for isomer separation,yields derivative (VI).(In turn,ketoester (V) can be obtained by treatment of 2-phenylethyl bromide (VII) with Mg turnings in refluxing THF,followed by reaction of the resulting Grignard reagent with diethyl oxalate (VIII) in THF).Finally,the desired product is obtained by saponification of the ethyl ester group of (VI) with NaOH.
参考文献标题:Synthesis of semisynthetic dipeptides using N-carboxyanhydrides and chiral induction on Raney nickel.A method practical for large scale
文献作者:Blacklock,T.J.; et al.
参考来源:J Org Chem 1988,53(4),836
产品链接: CAS No. 84680-54-6›› 产品链接: CAS No.76420-72-9››