Preparation and application of mitochondrial fluorescent dye 3-heteroaryl substituted-2h-indazole derivatives

Abstract

The invention relates to a synthesis method and an application of 3-heteroaryl substituted-2H-indazole derivatives for specifically labeling mitochondria. The 3-heteroaryl substituted-2H-indazole derivatives can be used for specifically labeling mitochondria to realize fluorescence imaging. A fluorescence emission spectrum of the derivatives can reach to an infrared / near infrared area, the maximum Stokes displacement can reach 178nm, and the derivatives have the advantages of very small molecular weight, small size, easy penetration of cell membranes and entrance to cells, good light stability and small cytotoxicity. The preparation method is characterized in that the 3-heteroaryl substituted-2H-indazole derivatives are obtained through a C-H / C-H direct oxidative cross-coupling reaction of 2H-indazole derivatives and electron-rich heterocycles under the catalysis of a transition metal. Compared with traditional C-X / C-M coupling and other methods, the method provided by the invention has the advantages of avoiding of tedious pre-activation processes of a substrate, improvement of the function group tolerance, simple reaction conditions, synthesis step simplification, total yield increase and cost reduction. Compared with preset expensive commercial mitochondrial labeling reagents, the 3-heteroaryl substituted-2H-indazole derivatives have high market competitiveness.

Description

technical field [0001] The invention relates to the preparation and application of a class of fluorescent compound 3-heteroaryl substituted-2H-indazole derivatives for specific labeling of mitochondria. Background technique [0002] Mitochondria are important organelles in most eukaryotic cells. In addition to providing energy for cells, they also participate in many physiological activities, such as cell differentiation, cell proliferation, intercellular information transmission, and cell apoptosis. They also have the ability to regulate cell growth. and cell cycle capacity [see: (a) Green, D.R.; Reed, J.C.Science.1998, 281, 1309; (b) Li, H.; Kolluri, S.K.; , 1159; (c) Maechler, P.; Wollheim, C.B. Nature. 2001, 414, 807; (d) Henze, K.; Martin, W. Nature. 2003, 426, 127; (e) Green, D.R.; Kroemer, G.Science.2011, 333, 1109; (f) Nunnari1, J.; Suomalainen, A. Cell. 2012, 148, 1145; (g) Friedman, J.R.; Nunnari, J. Nature.2014, 505, 335.] . Specific tracking and detection of t...

AI Technical Summary

Problems solved by technology

These two types of reactions usually have disadvantages such as long synthetic routes, many steps, harsh reaction conditions, cumbersome operations, difficult to obtain raw materials, poor tolerance of functional groups, and easy environmental pollution by by-products, which largely limits the rapid Synthesis of biheteroaryl compounds with excellent photophysical properties and specific fluorescence imaging effect on mitochondria

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