Semisynthesis of new tetrahydrofuranic alkyl ester and furano-pyrone derivatives as inhibitors of the mitochondrial complex I

Methoxymethylation of altholactone () led to the corresponding O-methoxymethyl derivative () in addition to the unexpected 6,7-dihydro-7-methoxy analogue (), and two original tetrahydrofuranic (THF) alkyl esters ( ,). Moreover, when we accomplished a new method for the preparation of the furano-pyrone goniofupyrone () through 7-hydroxylation of in acid medium, a minor compound () with an identical skeleton to that of compounds and was identified. Careful examination of the published spectral data of the reported styryl-lactones with an heptolide skeleton reveals that those structures possess also a THF alkyl ester skeleton. The revision of those structures was confirmed by chemical correlation. All altholactone derivatives assayed proved to be specific inhibitors of the mitochondrial complex I.