ASYMMETRIC REDUCTIVE ALKYLATION OF ALANYLPROLINE BY THE ETHYL ESTERS OF 4-SUBSTITUTED 2-OXOBUTENOIC ACIDS

Authors

  • В. А. Славинская Latvian Institute of Organic Synthesis, Riga LV 1006
  • Дз. Э. Силе Latvian Institute of Organic Synthesis, Riga LV 1006
  • Г. И. Чипенс Latvian Institute of Organic Synthesis, Riga LV 1006
  • Ю. Ю. Балодис Latvian Institute of Organic Synthesis, Riga LV 1006
  • Г. Ф. Розенталь Latvian Institute of Organic Synthesis, Riga LV 1006
  • К. К. Вентерис Latvian Institute of Organic Synthesis, Riga LV 1006
  • Э. Лукевиц Latvian Institute of Organic Synthesis, Riga LV 1006

Keywords:

alanylproline, angiotensin-converting enzyme inhibitors, palladium black, 4-substituted ethyl 2-oxobutenoates, asymmetric reductive alkylation

Abstract

A method was developed for the synthesis of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]alanylproline (enalapril) by reductive alkylation of alanylproline with ethyl 2-oxo-4-phenylbutenoate under the conditions of hydrogenation in the presence of palladium black and 1.6% Pd/C. The yield of enalapril amounted to 65%. With the ethyl ester of the α-oxo acid the diastereoselectivity of formation of the S,S,S-diastereomer was higher than with the saturated synthon. It is assumed that with ethyl 2-oxo-4-phenylbutenoate as synthon a conformationally restricted surface complex is formed between the unsaturated synthon and the active centers of the catalyst. During reductive alkylation of alanylproline by ethyl 2-oxo-4-(2-thienyl)butenoate poisoning of the catalyst occurs.

How to Cite
Slavinska, V.; Sile, Dz.; Chipens, G. I.; Balodis, Yu.; Rozenthal, G.; Venteris, K.; Lukevics, E. Chem. Heterocycl. Compd. 2003, 39, 1579. [Khim. Geterotsikl. Soedin. 2003, 1794.]

For this article in the English edition, see DOI 10.1023/B:COHC.0000018334.85109.3f

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Published

2003-12-25

Issue

No. 12 (2003)

Section

Original Papers