0000000000083067
AUTHOR
Eva Peris
Semisynthesis of new tetrahydrofuranic alkyl ester and furano-pyrone derivatives as inhibitors of the mitochondrial complex I
Abstract Methoxymethylation of altholactone ( 1 ) led to the corresponding O -methoxymethyl derivative ( 3 ) in addition to the unexpected 6,7-dihydro-7-methoxy analogue ( 4 ), and two original tetrahydrofuranic (THF) alkyl esters ( 5 , 6 ). Moreover, when we accomplished a new method for the preparation of the furano-pyrone goniofupyrone ( 7 ) through 7-hydroxylation of 1 in acid medium, a minor compound ( 8 ) with an identical skeleton to that of compounds 5 and 6 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 structure…
3-acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors.
A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone and 5-acetoxyisogoniothalamin oxide, have been isolated from Goniothalamus arvensis (Annonaceae) stem bark. We report here the isolation and structural elucidation of these compounds with furane-pyrone and styryl-pyrone skeletons, postulating also for the first time their mechanism of cytotoxicity based on inhibition on mammalian mitochondrial respiratory chain.
Analogues of cytotoxic squamocin using reliable reactions: new insights into the reactivity and role of the α,β-unsaturated lactone of the annonaceous acetogenins
Abstract A small library of squamocin analogues has been prepared and screened biologically (cytotoxicity, inhibition of mitochondrial complex I and complex III). To centre diversity on a crucial part of the molecule (i.e., the α,β-unsaturated lactone), an original and reliable lactone opening reaction has been discovered and exploited among other efficient reactions.
Inhibitory effects on mitochondrial complex I of semisynthetic mono-Tetrahydrofuran acetogenin derivatives
Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety or in the alkyl chain that links this terminal gamma-lactone with the alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.