Department of Organic Chemistry, University of Szeged, Szeged, Hungary.
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):895-902. doi: 10.1080/14756366.2021.1900165.
Facile syntheses of 3--carbamoyl, -sulfamoyl, or -pivaloyl derivatives of 13α-oestrone and its 17-deoxy counterpart have been carried out. Microwave-induced, Ni-catalysed Suzuki-Miyaura couplings of the newly synthesised phenol esters with phenylboronic acid afforded 3-deoxy-3-phenyl-13α-oestrone derivatives. The carbamate and pivalate esters proved to be suitable for regioselective arylations. 2-(4-Substituted) phenyl derivatives were synthesised via Pd-catalysed, microwave-assisted C-H activation reactions. An efficient, one-pot, tandem methodology was elaborated for the introduction of the carbamoyl or pivaloyl group followed by regioselective C-2-arylation and subsequent removal of the directing group. The antiproliferative properties of the novel 13α-oestrone derivatives were evaluated on five human adherent cancer cell lines of gynaecological origin. 3-Sulfamate derivatives displayed substantial cell growth inhibitory potential against certain cell lines. The newly identified antiproliferative compounds having hormonally inactive core might be promising candidates for the design of more active anticancer agents.
已经成功合成了 13α-雌酮及其 17-去氧类似物的 3-氨甲酰基、-磺酰胺基或-特戊酰基衍生物。新合成的酚酯与苯硼酸在微波诱导、镍催化的 Suzuki-Miyaura 偶联反应中得到了 3-去氧-3-苯基-13α-雌酮衍生物。氨基甲酸酯和特戊酸酯被证明适合区域选择性芳基化。通过钯催化、微波辅助 C-H 活化反应合成了 2-(4-取代)苯基衍生物。阐述了一种高效、一锅法、串联方法，用于引入氨甲酰基或特戊酰基，然后进行区域选择性 C-2-芳基化，随后去除导向基团。新型 13α-雌酮衍生物的抗增殖特性在五种源自妇科的人贴壁癌细胞系上进行了评估。3-磺酰胺衍生物对某些细胞系表现出显著的细胞生长抑制潜力。新鉴定的具有非激素活性核心的抗增殖化合物可能是设计更有效抗癌药物的有前途的候选物。
