Enantioselective Total Synthesis of (−)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy
Elliot F. Hicks, Kengo Inoue, Brian M. Stoltz
Abstract
The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed through a regioselective aziridine ring opening.
Topics & Concepts
ChemistryDesymmetrizationEnantioselective synthesisAziridineRegioselectivityCycloadditionStereochemistryMethyl vinyl ketoneKetoneNucleophileRing (chemistry)Organic chemistryCatalysisAlkaloids: synthesis and pharmacologyChemical synthesis and alkaloidsTraditional and Medicinal Uses of Annonaceae