The optimal synthetic scheme for the potential nootropic drug GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester) was developed. Three synthetic schemes were tested, each of which included the following steps: 1) esterification of L-proline; 2) preparation of N-phenylacetylglycine; 3) formation of the peptide bond. Esterification of proline per Brenner and preparation of N-phenylacetylglycine via acylation of glycine with phenylacetyl chloride under Schotten—Baumann conditions were used in all synthetic schemes. Three methods for forming the peptide bond between N-phenylacetylglycine and the proline ester were tried (mixed anhydride under Anderson conditions, activated benzotriazole ester, and activated succinimide ester methods) and showed that the mixed anhydride method was optimal, giving a total yield of 42%.

中文翻译：

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开发潜在促智药物 GZK-111、N-Phenylacetylglycyl-L-Proline Ethyl Ester 的最佳合成方案

开发了潜在促智药物 GZK-111（N-苯基乙酰基甘氨酰-L-脯氨酸乙酯）的最佳合成方案。测试了三种合成方案，每个方案都包括以下步骤：1）L-脯氨酸的酯化；2) N-苯乙酰甘氨酸的制备；3) 肽键的形成。在所有合成方案中都使用了每布伦纳的脯氨酸酯化和通过甘氨酸与苯乙酰氯在 Schotten-Baumann 条件下酰化制备 N-苯乙酰甘氨酸。尝试了三种在 N-苯基乙酰甘氨酸和脯氨酸酯之间形成肽键的方法（安德森条件下的混合酸酐、活化苯并三唑酯和活化琥珀酰亚胺酯方法），结果表明混合酸酐方法是最佳的，总收率为 42 %。