Achmatowicz approach to the asymmetric synthesis of (+)- and (-)-monanchorin

The full account of our development of a de novo asymmetric total synthesis of (+)-monanchorin has been reported. The optimized synthesis provided access to either enantiomer of the guanidine alkaloid natural product in nine steps from the commodity chemicals furan and caproic acid. The route relied upon the asymmetric Noyori hydrogen transfer reduction of an achiral acylfuran to introduce the absolute stereochemistry. In addition, an Achmatowicz rearrangement, a diastereoselective palladium-catalyzed glycosylation, a reductive amination and an acid-catalyzed bicyclic guanidine mixed acetal formation were used to complete the synthesis.

Automated summary

The full account of a de novo asymmetric total synthesis of (+)-monanchorin, a guanidine alkaloid natural product, has been reported. The optimized synthesis route enables the access to both enantiomers of the compound in nine steps starting from the commodity chemicals furan and caproic acid. The synthesis relied on various reactions, including asymmetric Noyori hydrogen transfer reduction, Achmatowicz rearrangement, diastereoselective palladium-catalyzed glycosylation, reductive amination, and acid-catalyzed bicyclic guanidine mixed acetal formation.