N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, 119991.
D. I Mendeleev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow, Russia, 125047.
Mol Divers. 2020 Nov;24(4):1327-1342. doi: 10.1007/s11030-019-09997-6. Epub 2019 Oct 23.
A novel five-component diastereoselective synthesis of polysubstituted 2-piperidinones is reported. The Knoevenagel condensation-Michael addition-Mannich cascade of two equivalents of aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate or aqueous ammonia in alcohols provides convenient access to alkyl (3SR,4RS,6SR)-5,5-dicyano-2-oxo-4,6-diarylpiperidine-3-carboxylates with three stereocenters in 52-90% or dialkyl (2SR,3RS,4RS,5SR)-2,4-diaryl-3-cyano-6-oxopiperidine-3,5-dicarboxylates with four stereocenters in 38-88%. The formation of products was highly stereoselective, with only one diastereomer formed. Ammonium acetate or aqueous ammonia plays a role both as a catalyst and as a nitrogen source. 2,4,6-triaryl-3,3,5,5-tetracyanopiperidines were obtained as a side products in the reactions with nitro-substituted aldehydes or with ethyl and n-propyl cyanoacetates. A series of 14 2-piperidinones and piperidines was assessed for antimicrobial activity against a panel of five bacteria and two fungi; no significant activity was observed. Two side piperidines with nitro substituents in aromatic ring possess bacteriostatic action against S. aureus ATCC 43300 and A. baumannii ATCC 19606 at 32 ug/mL.
报道了一种新型的五组分非对映选择性合成多取代 2-哌啶酮的方法。在醇中，通过芳香醛、腈、二烷基丙二酸酯和乙酸铵或氨水的克脑文格尔缩合-迈克尔加成-曼尼希级联反应，两个当量的上述物质可以方便地得到具有三个手性中心的烷基（3SR,4RS,6SR）-5,5-二氰基-2-氧代-4,6-二芳基-3-哌啶羧酸酯，产率为 52-90%，或者得到具有四个手性中心的二烷基（2SR,3RS,4RS,5SR）-2,4-二芳基-3-氰基-6-氧代-3,5-哌啶二羧酸酯，产率为 38-88%。产物的形成具有高度的立体选择性，只形成一种非对映异构体。乙酸铵或氨水既作为催化剂又作为氮源发挥作用。在与硝基取代的醛或与乙基和正丙基氰基乙酸酯的反应中，得到了 2,4,6-三芳基-3,3,5,5-四氰基哌啶作为副产物。对 14 种 2-哌啶酮和哌啶进行了一系列抗菌活性评估，针对五种细菌和两种真菌；未观察到显著的活性。两个具有芳香环硝基取代基的侧哌啶在 32 ug/mL 时对金黄色葡萄球菌 ATCC 43300 和鲍曼不动杆菌 ATCC 19606 具有抑菌作用。
