Asymmetric Synthesis of Gonioheptolide A Analogues via an Organocatalytic Aldol Reaction as the Key Step

Abstract

An efficient asymmetric synthesis of the potential antitumor agent (–)-gonioheptolide A derivatives is described. By employing an (S)-proline-catalyzed aldol reaction, the RAMP hydrazone α-alkylation methodology, and a diastereoselective reduction with zinc borohydride five stereocenters are established in the target compound. 4-epi-Methoxy-gonioheptolide A was obtained in ten steps in 15% overall yield and excellent diastereo- and enantiomeric excesses (de ≥95%, ee ≥99%).

Key words

dihydroxyacetone - aldol reaction - organocatalysis - proline - styryllactone

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