A Combined Experimental and Density Functional Theory Study on the Pd-Mediated Cycloisomerization of o-Alkynylnitrobenzenes - Synthesis of Isatogens and Their Evaluation as Modulators of ROS-Mediated Cell Death

作者：Ramana Chepuri V^*; Patel Pitambar; Vanka Kumar; Miao Benchun; Degterev Alexei

来源：European Journal of Organic Chemistry, 2010, 2010(31): 5955-5966.

DOI：10.1002/ejoc.201000769

• Nitro-alkyne cycloisomerization
• Cyclization
• Palladium
• Isatogens
• Anthranil
• Density functional calculations

Highly selective cycloisomerization of o-alkynylnitrobenzenes, leading to isatogens, has been achieved by employment of a Pd-II complex. This reaction is very general and functional-group-tolerant. The possible mechanism of this reaction was investigated with the help of DFT calculations. Three possible pathways - namely, the addition of the nitro group either in (i) 5-exo-dig or (ii) 6-endo-dig mode and (iii) halopalladation - and subsequent intramolecular events have been considered and studied in detail. These investigations revealed that pathway (i) is the favored route to isatogen formation. A preliminary screening of the available isatogens reveals the 2-alkylisatogens to be novel ROS scavengers capable of inhibiting cellular necroptosis.

• 出版日期2010-11