Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, Hungary.
Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, H-6720 Szeged, Hungary.
Molecules. 2023 Dec 5;28(24):7962. doi: 10.3390/molecules28247962.
A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner-Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic -substituted derivatives. The antiproliferative effects were assayed using the MTT method.
一系列新型二萜型 1,3-氨基醇及其区域异构体已通过立体选择性方式从天然甜菊糖甙合成得到。使用来自甜菊醇甲酯的环氧化物的 Wagner-Meerwein 重排制备关键的中间体β-酮醇。通过 Raney 镍催化肟的氢化形成伯氨基醇，并且使用伯胺的席夫碱合成了多种氨基醇库。通过β-酮醇的甲磺酸酯制备氨基醇的区域异构体。通过钯催化氢化羟基叠氮化物形成相应的伯氨基醇，并且还进行了后者的点击反应。使用 1D 和 2D-NMR 技术和 HRMS 测量对新化合物进行了表征。体外研究表明，萘取代衍生物在人癌细胞系（HeLa、SiHa、A2780、MCF-7 和 MDA-MB-231）中显示出高的细胞生长抑制作用。使用 MTT 法测定抗增殖作用。
