Synthesis of Sphingosine-Related Azetidine Alkaloids, Penaresidins: Construction of Highly Substituted Azetidine Rings

Penaresidin A and B are sphingosine-related natural products that contain a 2,3,4-trisubstituted azetidine ring and a long alkyl side chain. Stereoselective construction of the trisubstituted azetidine ring is a crucial step in the synthesis of penaresidins, and all the currently reported syntheses have been accomplished by SN2-type cyclization of a precursor having a 1-amino-2,3-diol structure with three continuous stereocenters. This cyclization is strongly influenced by the configurations of the vicinal amino alcohol moieties of the precursors. This review focuses on the SN2-type cyclizations that are used to construct the trisubstituted azetidine ring in penaresidin synthesis. Dedicated to Professor Kaoru Fuji on the occasion of his 80th birthday CONTENTS 1. Introduction 2. Construction of azetidine rings from 2-amino precursors 2.1 Construction after introduction of the side chain 2.2 Construction before introduction of the side chain 3. Construction of azetidine rings from 4-amino precursors 4. Conclusions