RESUMO
Dimeric indolosesquiterpene alkaloids, typically N-N- and C-N-linked xiamycin dimers, feature a pentacyclic framework with four contiguous stereogenic centers at the periphery of a trans-decalin scaffold to which a carbazole unit is attached. In comparison with actual biosynthetic dixiamycin derivatives, we designed C-C-linked xiamycin dimers, aiming to use them as a powerful tool to create unique scaffolds as drug candidates. In this work, we disclose the first synthetic route to access a C-C dimeric indolosesquiterpene skeleton, featuring a hypervalent iodine (PIFA)-catalyzed oxidative dimerization reaction in a single-step operation with overwhelming control over the chemoselectivity and regioselectivity. This strategy has been successfully applied to the synthesis of a C-C dimer of xiamycin A (3) and xiamycin A methyl ester (15) that demonstrates a new synthetic pathway for dimeric indolosesquiterpene alkaloids.
RESUMO
N-N dimeric indolosesquiterpene alkaloids constitute a class of under-investigated architecturally intriguing natural products. Herein, we report the first chemical oxidation approach to the asymmetric total syntheses of these atropisomeric indolosesquiterpenoids through N-N bond formation. Specifically, dixiamycins A (1a) and B (1b) were prepared through a Cu(i)-mediated aerobic dehydrogenative dimerization from the naturally occurring monomer xiamycin A methyl ester (2b); this preparation also represents the first total synthesis of dixiamycin A (1a). The monomer xiamycin A methyl ester (2b) was synthesized via a late-stage Buchwald Pd(ii)-mediated aerobic dehydrogenative C-N bond formation.
