AZA-quinone methides

QUINONE METHIDES AND AZA-QUINONE METHIDES AS LATENT ALKYLATING SPECIES IN THE DESIGN OF MECHANISM-BASED INHIBITORS OF SERINE PROTEASES AND p-LACTAMASES... 

QUINONE METHIDES AND AZA-QUINONE METHIDES AS LATENT ALKYLATING... 

However, there are two problems with these unconjugated lactones lack of selectivity and limited stability of the inhibitor in biological buffers. Coumarin carboxylates have been developed to improve selectivity toward a given serine protease (Section 11.4.1). On the other hand, the amide bond is chemically and enzymatically much more stable than the ester one. This raised the question of whether a starting functionalized lactam behaved like the previous lactones and generated in situ a quinonimine methide, the aza-analogue of the quinone methide (Section 11.5). 

The studies described above show that a quinone methide or its aza-analogue quinonimine methide incorporated as a latent electrophilic species into a cyclic lactone or lactam precursor can modify a second nucleophilic residue within the enzyme active site after formation of the acyl-enzyme. Very efficient suicide... 

Aza analogs of cyclopentadiene and cyclononatetraene rings could act as acceptor parts in push-pull systems, and possibly be more powerful than their carbocyclic analogs, but no stereochemical studies of such systems seem to have been reported. The remaining group of systems with potentially aromatic acceptors, the quinone methides, have a number of counterparts in heterocyclic chemistry. 

Edwards, J. M., and U. Weiss Quinone Methides Derived from 5-Oxa- and 5-Aza-9-Phenyl-l-Phenalenone in the Flowers of Lachnanthes tinctoria. Tetrahedron Letters 1631 (1972). 

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