ABSTRACT
Enantioselective construction of small molecules displaying a configurationally stable helical shape built on a fused-tetracyclic core is a daunting synthetic challenge even more pronounced when five-membered rings are incorporated in the structure. The resulting higher configurational lability strongly hampers their access, and therefore the development of new efficient methodologies is timely and highly desirable. In this context, we describe a padlocking approach via the enantioselective organocatalytic domino furannulation of appropriately designed achiral fused-tricyclic precursors resulting in the synthesis of configurationally locked helically chiral tetracyclic scaffolds featuring one or two five-membered rings with the simultaneous control of central and helical chiralities.
ABSTRACT
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.
