Asymmetric total synthesis of rhinacanthin A

Starting from a reduced lapachol compound, the total synthesis of rhinacanthin A in both racemic and enantioenriched forms is achieved in eight steps without forming any undesired β-lapachone derivatives. For the synthesis of enantioenriched rhinacanthin A, the introduction of the asymmetric center was carried out by using the catalytic asymmetric epoxidation of an unfunctional trisubstituted olefin using Shi’s epoxidation diketal catalyst. The acidic treatment of a derived enantioenriched epoxynaphthol and the following CAN oxidation afforded the target molecule with high enantiomeric purity.

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2-tert-Butyldimethylsilyloxy-1,4-dimethoxy-3-((3,3-dimethyloxiran-2-yl)methyl)naphthaleneC23H34O4SiEe = 83%[α]D24=-10.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-3,4-Dihydro-3-hydroxy-5,10-dimethoxy-2,2-dimethyl-2H-naphtho[2,3-b]pyranC17H20O4Ee = 83%[α]D24=-6.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-3,4-Dihydro-3-hydroxy-5,10-2,2-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione (rhinacanthin A)C15H14O4Ee = 82%[α]D24=-14.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)