THIOPHILIC RING-OPENING AND REARRANGEMENT REACTIONS OF EPOXYKETONE NATURAL-PRODUCTS

Thiol additions to the highly functionalized core structures of aranor osin- and manumycin-type antibiotics reveal the general reactivity pat terns of epoxyketone natural products. Rapid hemiacetal and hydrate fo rmations decrease the reactivity of the epoxyketone moiety in aqueous media toward the cellular scavenger glutathione, and secondary 1,2-shi ft, elimination, aromatization and intramolecular aldol reactions prov ide novel reaction pathways. In a hydrophobic environment, the thiol-c apture function of the ketone moiety facilitates electrophilic attack. (C) 1998 Elsevier Science Ltd. All rights reserved.