Synthesis ( IF 2.2 ) Pub Date : 2018-10-25 , DOI: 10.1055/s-0037-1611065 Christopher Jones 1 , Weitao Sun 1 , Piera Trinchera 1 , Nada Kurdi 1 , David Palomas 1 , Rachel Crespo-Otero 1 , Saeed Afshinjavid 2 , Farideh Javid 2
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Abstract
This is a full account of our studies into the generation of highly functionalised 2-aryl-1,2-dihydropyridines and 2-methylene-3-aryl-1,2,3,4-tetrahydropyridines via intermolecular aryne ene reactions of Hantzsch esters. Furthermore, exposure to excess aryne revealed unusual 3′-aryl-spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]. Mechanistic insights are provided by deuterium-labelling studies and DFT calculations, whilst preliminary cytotoxicity investigations reveal that the spirocycles are selective against colon carcinomas over ovarian cancer cell lines and that all the compounds have high selectivity indices with regards to non-cancer cells.
This is a full account of our studies into the generation of highly functionalised 2-aryl-1,2-dihydropyridines and 2-methylene-3-aryl-1,2,3,4-tetrahydropyridines via intermolecular aryne ene reactions of Hantzsch esters. Furthermore, exposure to excess aryne revealed unusual 3′-aryl-spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]. Mechanistic insights are provided by deuterium-labelling studies and DFT calculations, whilst preliminary cytotoxicity investigations reveal that the spirocycles are selective against colon carcinomas over ovarian cancer cell lines and that all the compounds have high selectivity indices with regards to non-cancer cells.
中文翻译：
芳烃介导的Hantzsch酯化：获得高度取代的芳基-二氢吡啶，芳基-四氢吡啶和螺[苯并环丁烯-1,1'-（3'，4'-二氢吡啶）]
摘要
这充分说明了我们通过Hantzsch酯的分子间亚芳基烯反应生成高度官能化的2-芳基-1,2-二氢吡啶和2-亚甲基-3-芳基-1,2,3,4-四氢吡啶的研究。此外，暴露于过量的芳烃中发现不寻常的3'-芳基-螺[苯并环丁烯-1,1'-（3'，4'-二氢吡啶）]。氘标记研究和DFT计算提供了机理上的见解，而初步的细胞毒性研究表明，螺环对卵巢癌细胞系对结肠癌具有选择性，并且所有化合物对非癌细胞的选择性都很高。
这充分说明了我们通过Hantzsch酯的分子间亚芳基烯反应生成高度官能化的2-芳基-1,2-二氢吡啶和2-亚甲基-3-芳基-1,2,3,4-四氢吡啶的研究。此外，暴露于过量的芳烃中发现不寻常的3'-芳基-螺[苯并环丁烯-1,1'-（3'，4'-二氢吡啶）]。氘标记研究和DFT计算提供了机理上的见解，而初步的细胞毒性研究表明，螺环对卵巢癌细胞系对结肠癌具有选择性，并且所有化合物对非癌细胞的选择性都很高。
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