目的深入探讨基于羟基亚乙基二肽的β-分泌酶抑制剂的合成方法。方法综合使用多种有机合成反应来合成拟肽类β-分泌酶抑制剂,包括亲核性加成反应、有机金属试剂协助的取代反应、催化氢化反应、传统多肽偶联反应等。结果以目标化合物之一化合物13作为模型物,通过成功合成化合物13建立了反应条件优化的合成方法。结论本文建立的合成方法可用于构建β-分泌酶抑制剂化学库,发现新的有效化合物。 OBJECTIVE: To study the synthesis of β-secretase inhibitors based on hydroxyethylene dipeptide. Methods The synthesis of peptidomimetics β-secretase inhibitors using a variety of organic synthesis reactions, including nucleophilic addition reactions, organometallic reagent-assisted substitution reactions, catalytic hydrogenation reactions, and traditional peptide conjugation reactions, were synthesized. Results As a model compound, one of the target compounds was used as the model compound to synthesize compound 13 successfully. Conclusion The synthetic method established in this paper can be used to construct β-secretase inhibitor chemical library and find new effective compounds.