Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent pr...Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22077099,22171223 and 22307102)the Innovation Capability Support Program of Shaanxi(Nos.2023-CXTD-75 and 2022KJXX-32)+5 种基金the Technology Innovation Leading Program of Shaanxi(Nos.2023KXJ-209 and 2024QCY-KXJ-142)the Key Research and Development Program of Shaanxi(No.2024GHZDXM-22)the Natural Science Basic Research Program of Shaanxi(Nos.2023-JC-YB-141 and 2022JQ-151)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(Nos.22JHZ010 and 22JHQ080)the Yan’an City Science and Technology Project(No.2022SLZDCY-002)。
文摘Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.
