Synthetic studies towards naturally occurring aporpinones: asymmetric synthesis of 1'-deshydroxymethyl analogues of aporpinone A, aporpinone B and 4'-hydroxyaporpinone A.

Abstract

Herein, we disclose the asymmetric total synthesis of 1'-deshydroxymethyl analogues of naturally occurring aporpinone A, aporpinone B, and 4'-hydroxyaporpinone A, featuring a γ-Z-alkylidene butenolide framework. Bimetallic (Pd-Cu) cascade cyclization on a properly functionalized bis-alkyne with Z-2-bromoacrylic acid was employed to construct the butenolide framework with an alkyne appendage. Late-stage enzymatic kinetic resolution (EKR) was adopted for the synthesis of (R)-1'-deshydroxymethyl aporpinone A and (S)-1'-deshydroxymethyl acetyl aporpinone A. The enantiopure bis-alkyne required for the synthesis of (S)-1'-deshydroxymethyl aporpinone B and (R)-1'-deshydroxymethyl 4'-hydroxyaporpinone A was constructed through the Sonogashira cross-coupling reaction.