Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

Abstract

Most heteroaryl selenides and diselenides are biologically active, with some reported to act as antioxidants and show activities that are medicinally relevant; hence, the development of efficient methods for their synthesis is an important objective. Herein, a simple method for the synthesis of selenides and diselenides bearing imidazo[1,2-a]pyridine rings and their anticancer activity are described. The double C–H selenation of imidazo[1,2-a]pyridine with Se powder was catalyzed by CuI (10 mol %) ligated with 1,10-phenanthroline (10 mol %) at 130 °C under aerobic conditions. The selenides or diselenides were prepared almost selectively using selenium powder in an appropriate quantity under otherwise identical reaction conditions. The prepared selenides and diselenides bearing two imidazo[1,2-a]pyridine rings were all novel compounds. Among the prepared diselenides and selenides that exhibited cytotoxicity against cancer cells, bis[2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-yl] diselenide showed an excellent anticancer activity and low cytotoxicity toward noncancer cells, suggesting that this diselenide is a potential lead compound for anticancer therapy.

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

“…A Cu-catalyzed cross-coupling reaction using benzene ring substituted diaryl diselenides with terminal alkynes in the presence of bases is effective for synthesizing aryl alkynyl selenides [ 27 – 31 ]. We previously reported a simple method for the synthesis of bis(2-arylimidazo[1,2- a ]pyridin-3-yl) diselenides using a Cu-catalyzed C–H selenation at the 3-position of 2-arylimidazo[1,2- a ]pyridines with Se powder [ 32 ]. Initially, the reaction of bis(2-phenylimidazo[1,2- a ]pyridin-3-yl) diselenide ( 2a ), generated from Se powder and 2-phenylimidazo[1,2- a ]pyridine ( 1a ), with phenylacetylene ( 3a ) was used as a model reaction to determine a suitable base and an equivalent number of reagents ( Table 1 ).…”

“…Initially, the reaction of bis(2-phenylimidazo[1,2- a ]pyridin-3-yl) diselenide ( 2a ), generated from Se powder and 2-phenylimidazo[1,2- a ]pyridine ( 1a ), with phenylacetylene ( 3a ) was used as a model reaction to determine a suitable base and an equivalent number of reagents ( Table 1 ). The key intermediate 2a was prepared in situ from 1a (0.5 mmol) and Se powder (0.5 mmol) in the presence of 10 mol % of CuI and 1,10-phenanthroline at 130 °C in DMSO under aerobic conditions without bases using the method reported previously [ 25 , 32 ]. The reaction mixture was then treated with phenylacetylene ( 3a , 0.5 mmol) and various bases at room temperature.…”

“…This reaction, without Na 2 CO 3 as base, also afforded 4aa in 85% yield ( Scheme 1 , reaction 1). Although bis(imidazo[1,2- a ]pyridin-3-yl)monoselenides 5 could form in situ [ 32 ], the reaction of 5 with acetylene 3a under the standard conditions did not proceed ( Scheme 1 , reaction 2).…”

Reaction of imidazo[1,2-a]pyridines with coumarin-3-carboxylic acids: a domino Michael addition/decarboxylation/oxidation/annulation

“…Given the pharmacological activities of C-3 functionalized imidazo[1,2- a ]pyridines, direct functionalization of the C3 position of this class of compound via carbon–carbon and carbon–heteroatom bond forming reactions, under metal-catalyzed or metal-free conditions, has attracted much attention. For example, a variety of chalcogen sources such as thiocyanates 10 (Zhou 2020), thiols 11 (Yaun 2018), elemental sulfur, 12 tetraalkylthiuram disulfide 13 (Zhan 2021), disulfides 14 (Braga 2018), elemental selenium 15 (Yasuike 2019), sulfonyl chlorides and DMSO 16 (Ravi 2016), and ethylarylsulfinates 17 (Sun 2021) have been employed to construct imidazopyridines with carbon-chalcogen bonds.…”

Synthesis and Biological Activities of Selenium/Thioether Quinazoline Compounds

“…8 A series of 2,4-disubstituted quinazolines were synthesized by Li 9 and Buggana, 10 which have excellent antitumor activities against five tumor cells (MDA- . Selenides and diselenides containing imidazole or pyridine moieties, synthesized by Matsumura,11 showed good anticancer activities and low toxicity of non-target cells. In recent years, the biological activities of 4-aminoquinazoline derivatives 12 and 4-thioquinazoline derivatives 13 have been extensively studied.…”