Synthesis of Palhinine A and D
Total Synthesis of Lycopodium Alkaloids Palhinine A and Palhinine D.
J. Am. Chem. Soc. 2017;
16 May 2017 (online)
Key wordspalhinine A and D - Lycopodium alkaloids - nitrone - isooxazolidine - 1,3-dipolar cycloaddition
Palhinine A and D are members of the Lycopodium alkaloid family isolated from the whole plant of Palhinhaea cernua L. Fan and co-workers describe the first total syntheses relying on a microwave-assisted regio- and stereoselective nitrone-alkene [3+2] cycloaddition as the key step to access the nine-membered azanone ring system.
Treatment of hydroxylamine E with formalin in CH2Cl2 resulted in the formation of nitrone F, which underwent an intramolecular 1,3-dipolar cycloaddition to give isoxazolidine G. N-Alkylation followed by reductive N–O cleavage gave access to the challenging azanone ring system, key structural motif of palhinine A and D.