Efficient, Isocyanide-Based Ugi Multi-component Reactions

2 Efficient, Isocyanide-Based Ugi Multi-component Reactions 

Why are Ugi s MCRs so efficient The answer hes in the low activation energies of all the elementary steps, which are either eqmlibrium processes or irreversible steps. This concept of energetically preferred reactions is discussed in Chap. 15, in relation to click-reactions of azides and alkynes. Low-energy elementary reactions either occur in concert and are pericychc or involve two reacting groups with highly matching electron distribution. 

The high nucleophilic character of the isocyanide group can be explained by the ambivalent electronic nature of the two-valent carbon atom of this group, which determines its extraordinary reactivity (Fig. 8.1) [46]. 

The high reactivity of isocyanides and cyanides is due to the atomic coefficients of their respective HOMO/LUMO orbitals. Compared to alkyl nitriles, the atomic 

representative of the library of potent inhibitors of haematopoetic (blood-forming) protein-tyrosine phosphatase, was reported by chemists at Ontogen [47, 48]. Compound 34 exhibited high activity at micromolar concentrations (IC50 3.9 pM) [47]. Since this enzyme is over-expressed in acutely leukemic cells, these compoimds exhibited a promising biological profile for the treatment of leukemia. 

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