Total Syntheses of (–)-7-epi-Alexine and (+)-Alexine Using Stereoselective Allylation

Abstract

Total syntheses of (–)-7-epi-alexine and (+)-alexine were achieved by using stereoselective allylation via a functionalized pyrrolidine obtained from an extended chiral 1,3-oxazine. The synthetic strategies include pyrrolidine formation via oxazine cleavage and diastereoselective allylations of a pyrrolidine aldehyde. (–)-7-epi-Alexine and (+)-alexine were synthesized from anti,syn,anti-oxazine in 12 steps.

Recent advances on the synthesis of natural pyrrolizidine alkaloids: alexine, and its stereoisomers

“…In another study, Myeong and Ham achieved the total synthesis of alexine 1 and (−)-7-epi-alexine 13 from anti,syn,anti-oxazine 153 [53]. Treatment of diol 153 (obtained from 152) [54] with 2,2-dimethylpropanoyl chloride (PivCl) gave compound 154, which was mesylated, followed by oxazine ring cleavage, and simultaneously induced cyclization to afford functionalized pyrrolidine 155.…”

New Frontiers on Human Safe Insecticides and Fungicides: An Opinion on Trehalase Inhibitors

“…The first asymmetric synthesis of (+)-alexine (24) was accomplished by Yoda and co-workers in 2000 through synthetic elaboration of a key lactam derived from 2,3,5-tri-O-benzyl-β-arabinofuranose [75]. Since then, several other total syntheses of (+)-alexine (24) were reported [76][77][78][79].…”

Recent advances in the total synthesis of polyhydroxylated alkaloids via chiral oxazines

“…Compounds such as (+)-hyacinthacine A 2 (12), 17 containing four consecutive stereocenters, belong to this group. Additionally, other diastereomerically enriched natural products like (+)-australine (13), 16 (+)-alexine (14), 18 (−)-7-epi-alexine (15), 18 and (+)-casuarine (16) 19 are known to exist.…”