Multicomponent Passerini Approach to Important Targets

Since many types of tumor cells are associated with oxidative stress, Sasse, Jacob, and coworkers decided to use a Passerini MCR to elegantly synthesize a number of structures combining two, three, or even four redox ceuters with good yield, amoug them those contaiuiug multiple chal-cogen, porphyriu metal bindiug, and quinone redox sites (Fig. 8.5) [48]. 

Additionally, the compounds were then examined against cancer cells showing a clear inhibition of the ceU proliferation and inducing apoptotic cell death. Interestingly, some of these redox-active compounds exhibited quite low toxicity with normal cells. 

Although maybe Passerini condensation has been less successful in its application for preparing biologically relevant molecules in comparison with the Ugi reaction, mainly because in the Passerini reaction there are only three variables that can be introduced, thus limiting the application of intramolecular versions to prepare heterocycles, we reflect here two attractive examples. 

and coworkers applied the Passerini 3-MCR approach as the final key step for the synthesis of interesting podophyUotoxin derivatives 60 with good yields (36-85%) (Schane 8.21) [49]. 

The in vitro cytotoxicity of final Passerini adducts was evaluated against four human tumor cell lines A549 (nonsmall ceU lung cancer), DU145 (prostate cancer ceU line). 

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