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.