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Fluorinated phosphonate analogues of phenylalanine: synthesis, X-ray and DFT studies
Arabian Journal of Chemistry ( IF 6 ) Pub Date : 2020-01-01 , DOI: 10.1016/j.arabjc.2018.05.002
Joanna Kwiczak-Yiğitbaşı , Jean-Luc Pirat , David Virieux , Jean-Noël Volle , Agnieszka Janiak , Marcin Hoffmann , Donata Pluskota-Karwatka

Abstract Due to their biological activity and structural analogy to corresponding α-amino acids, α-aminophosphonates and their fluorinated derivatives provide an important source for drug discovery. Therefore convenient access to this class of compounds is still desirable. Four series of novel phosphonate analogues of fluorinated phenylalanine containing variable number of fluorine atoms in different positions of the phenyl ring were synthesized and subjected to solid state characterization by single-crystal X-ray diffraction analysis, and to studies with the use of NMR, HRMS and DFT methods. Such an approach provided valuable information in regard to preferable conformation, hydrogen bonds and also weak intermolecular interactions present in the crystals investigated. As analogues of naturally occurring compounds, the obtained α-aminophosphonates have a big potential for biological activity. Formation of some indolinylphosphonates as minor products arisen from intramolecular SNAr reactions show that aminophosphonates exhibiting an electronically depleted aromatic group, and possessing a fluorine atom in ortho position of the phosphonoalkyl substituent may give an entrance to further derivatives that may exhibit entirely new properties.

中文翻译:

苯丙氨酸的氟化膦酸酯类似物:合成、X 射线和 DFT 研究

摘要 由于其生物活性和与相应 α-氨基酸的结构相似性,α-氨基膦酸酯及其氟化衍生物为药物发现提供了重要来源。因此,仍然需要方便地获取此类化合物。合成了四个系列的氟代苯丙氨酸的新型膦酸酯类似物,在苯环的不同位置含有不同数量的氟原子,并通过单晶X射线衍射分析进行固态表征,并使用NMR、HRMS进行研究和 DFT 方法。这种方法提供了关于优选构象、氢键以及所研究晶体中存在的弱分子间相互作用的有价值的信息。作为天然存在的化合物的类似物,获得的α-氨基膦酸盐具有很大的生物活性潜力。一些吲哚基膦酸酯作为分子内 SNAr 反应产生的次要产物的形成表明,氨基膦酸酯显示出电子耗尽的芳族基团,并且在膦酰基烷基取代基的邻位具有氟原子,这可能为进一步的衍生物提供入口,这些衍生物可能表现出全新的特性。
更新日期:2020-01-01
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