Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania.
Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, LT-50254 Kaunas, Lithuania.
Molecules. 2023 Jan 21;28(3):1091. doi: 10.3390/molecules28031091.
In this paper, a simple and efficient synthetic route for the preparation of new heterocyclic amino acid derivatives containing azetidine and oxetane rings was described. The starting (-Boc-azetidin-3-ylidene)acetate was obtained from (-Boc)azetidin-3-one by the DBU-catalysed Horner-Wadsworth-Emmons reaction, followed by aza-Michael addition with NH-heterocycles to yield the target functionalised 3-substituted 3-(acetoxymethyl)azetidines. Methyl 2-(oxetan-3-ylidene)acetate was obtained in a similar manner, which was further treated with various (-Boc-cycloaminyl)amines to yield the target 3-substituted 3-(acetoxymethyl)oxetane compounds. The synthesis and diversification of novel heterocyclic amino acid derivatives were achieved through the Suzuki-Miyaura cross-coupling from the corresponding brominated pyrazole-azetidine hybrid with boronic acids. The structures of the novel heterocyclic compounds were confirmed via H-, C-, N-, and F-NMR spectroscopy, as well as HRMS investigations.
本文描述了一种简单高效的合成含氮杂环氨基酸衍生物的方法，该方法涉及氮杂环丁烷和环氧乙烷环。起始原料（-Boc-氮杂环丁-3-亚基）乙酸酯由（-Boc）氮杂环丁-3-酮通过 DBU 催化的 Horner-Wadsworth-Emmons 反应得到，然后与 NH-杂环进行氮杂迈克尔加成反应，得到目标功能化的 3-取代 3-（乙酰氧甲基）氮杂环丁烷。类似地得到甲基 2-（氧杂环丁-3-亚基）乙酸酯，然后用各种（-Boc-环氨基）胺进一步处理，得到目标 3-取代 3-（乙酰氧甲基）氧杂环丁烷化合物。通过相应的溴代吡唑氮杂环丁烷杂化物与硼酸的铃木-宫浦交叉偶联反应，实现了新型杂环氨基酸衍生物的合成和多样化。通过 H-、C-、N-和 F-NMR 光谱以及高分辨率质谱（HRMS）研究证实了新型杂环化合物的结构。
