Konovalov Aleksandr V, Churusova Svetlana G, Aleksanyan Diana V, Rybalkina Ekaterina Yu, Aksenova Svetlana A, Peregudov Alexander S, Klemenkova Zinaida S, Kozlov Vladimir A
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334, Russia.
Russian University of Chemical Technology, Miusskaya pl. 9, Moscow, 125047, Russia.
Org Biomol Chem. 2023 Oct 25;21(41):8379-8392. doi: 10.1039/d3ob01309j.
Amino-functionalized phosphoryl compounds are among the most useful molecular scaffolds in medicinal chemistry, while the potential of their thiophosphorylated analogs, especially those having an alkylamino moiety, is still uncovered. This is mainly due to the lack of convenient synthetic routes to these organophosphorus derivatives. To address this issue, we have suggested the facile approaches to α-(aminomethyl)- and substituted/unsubstituted α-(aminobenzyl)diphenylphosphine sulfides based on either the sequential transformations of (hydroxymethyl)diphenylphosphine sulfide, with the Staudinger reaction of an azide derivative as the key stage, or the addition of PhP(S)H to hydrobenzamides followed by the acid hydrolysis. The compounds obtained were reacted with picolinyl chloride to yield functionalized amides which readily underwent direct cyclopalladation, resulting in new representatives of non-classical -metalated Pd(II) pincer complexes. The latter exhibit promising cytotoxic activity against several human cancer cell lines and apoptosis inducing ability along with the remarkable cytotoxic effects on doxorubicin-resistant cell sublines.
氨基官能化的磷酰化合物是药物化学中最有用的分子支架之一，而它们的硫代磷酰化类似物，尤其是那些含有烷基氨基部分的类似物的潜力仍未被发现。这主要是由于缺乏通往这些有机磷衍生物的便捷合成路线。为了解决这个问题，我们提出了基于（羟甲基）二苯基膦硫化物的顺序转化，以叠氮化物衍生物的施陶丁格反应为关键步骤，或者将PhP(S)H加成到氢化苯甲酰胺上然后进行酸水解，来制备α-（氨基甲基）-和取代/未取代的α-（氨基苄基）二苯基膦硫化物的简便方法。所得到的化合物与吡啶甲酰氯反应生成功能化酰胺，这些酰胺很容易进行直接环钯化反应，从而产生非经典金属化的Pd(II)钳形配合物的新代表物。后者对几种人类癌细胞系表现出有前景的细胞毒性活性和诱导凋亡的能力，同时对多柔比星耐药细胞亚系具有显著的细胞毒性作用。
