Asymmetric Reductive Alkylation of Alanylproline by the Ethyl Esters of 4-Substituted 2-Oxobutenoic Acids |
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Authors: | V. Slavinska Dz. Sile G. I. Chipens Yu. Balodis G. Rozenthal K. Venteris E. Lukevics |
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Affiliation: | (1) Latvian Institute of Organic Synthesis, Riga, LV-1006 |
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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 -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. |
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Keywords: | alanylproline angiotensin-converting enzyme inhibitors palladium black 4-substituted ethyl 2-oxobutenoates asymmetric reductive alkylation |
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