The metal-free cascade transformation of geldanamycin
benzoquinone
core is proposed at relatively mild conditions. This approach yields
new benzoxazole ansamycin antibiotics and enables their functionalization
in an atom-economic manner, irrespective of the type of amine used.
The analysis of the heterocyclization course reveals the dependence
of its rate on the nature of thepara-substituent
within the benzylamine moiety (EDG/EWG) and the strength of the base.
The reduction of the ansamycin core enables an increase in anticancer
potency and selectivity.