Polygonapholine: A Total Synthesis Questions the Identity for the Purported Structure of the Natural Product.

Polygonapholine was isolated in 1997 from the Polygonatum alte-lobatum rhizome. Based on spectroscopic data, it was assigned a structure comprising an unusual cis -2,6-disubstituted bis -aryl morpholine ring to which is attached a ( Z )-4-hydroxycinnamate as an amide and an ( E )-4-hydroxycinnamate as an ester. Being a meso compound, polygonapholine should not exhibit an optical rotation as reported. A total synthesis of the purported morpholine alkaloid presented herein reveals discrepancies between the synthetic and the natural product casting doubt on the originally proposed structure.