Research toward the synthesis of heliquinomycin

Heliquinomycin, a member of a rubromycin family of natural products, is a complex natural product consisting of a naphthoquinone and an isocoumarin which are linked through a 5,6-spiroketal functionality. The spiroketal also bears a glycosidic linkage. Previous work in our group has developed a method for generating both the naphthoquinone and isocoumarin portions of this natural product. The focus of this work was to develop a method for joining these two halves of the natural product while also allowing for the formation of the spiroketal. The specific goals accomplished include developing a method for extending the allyl-side chain of a model isocoumarin compound, functionalization of an olefin in preparation for forming the spiroketal structure and coupling of the naphthoquinone with the isocoumarin model via a nitrile-oxide [3+2] dipolar cycloaddition. Completion of the natural product will also require several oxidation state adjustments of the naphthoquinone moiety. To that end we were able to carry out the necessary transformations: opening an isoxazole ring, reduction of a quinone ring to an acetylated hydroquinone and oxidation of a trimethoxybenzene ring to a methoxy quinone in attempting a synthesis of the natural product Y-1005