Hydroquinones, by reduction

This concept has been extended. Thus the trione (696) rapidly and irreversibly inactivates human erythrocyte nucleoside phosphorylase (PNPase), which catalyzes the reversible phosphorylation of inosine and guanosine to the respective bases and ribose 1-phosphate. Inhibitors of this enzyme have several potential medical applications, for example, in the prevention of foreign tissue rejection, in the treatment of gout and malaria, and for the potentiation of antineoplastic nucleosides. Mechanistically the 5,8-dione (quinone) (696) enters the enzyme active site. An active-site nucleophilic residue subsequently converts the quinone moiety to a hydroquinone by reductive addition (701). The resulting hydroquinone affords an alkylating quinone methide species by elimination of HCl (702) and then traps a second nucleophilic enzyme residue by a Michael type reaction (703). Cross-linking of the active site rationalizes the observed potency <91B8480>. 

Although lithiation of hydroquinone had no useful outcome the 2-bromo derivative gave the 2-lithio intermediate by haloge-metal exchange and thence 2-methyfthio-1,4-dihydroxy benzene by reaction with dimethyldisulphide.togetherwith some hydroquinone by reduction (ref.159,160). 

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