Stereoselective Synthesis of a Ceramide Transporter Protein (CERT)-Dependent Ceramide-Trafficking Inhibitor, (1R,3S)-HPA-12, via Gold(I)-Catalyzed Cyclization of a Propargylic N-Hydroxylamine

Abstract

A ceramide transporter protein (CERT)-dependent ceramide-trafficking inhibitor, HPA-12, is efficiently synthesized using gold(I)-catalyzed cyclization of a propargylic N-hydroxylamine, which is prepared via a stereoselective nitrone–alkyne addition reaction. The resulting 4-isoxazoline is converted into a syn-1,3-amino alcohol through stereoselective reduction and reductive ring opening.

Key words

HPA-12 - gold - nitrone - 4-isoxazoline - stereoselective synthesis

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