Quinone methide chemistry of prekinamycins: 13C-labeling, spectral global fitting and in vitro studies

In this article, we address the presence of the prekinamycin quinone methide using the techniques of spectral global fitting and the 13C-labeling of the reactive centre. Two-electron reduction of a prekinamycin affords a long-lived quinone methide species that was characterised spectrally. A correlation was made between the calculated DeltaE (kcal/mol) values for quinone methide tautomerisation and cytostatic activity to support the postulate that the quinone methide plays a role in prekinamycin biological activity. We also prepared a stable quinone methide of prekinamycin and studied its solution chemistry directly.