title: Lessons from the Total Synthesis of (±) Phalarine: Insights Into the Mechanism of the Pictet-Spengler Reaction.
abstract: The furanobisindole alkaloid, phalarine, possesses a unique structural framework within the alkaloid family of natural products. Our laboratory recently disclosed the racemic total synthesis of phalarine, featuring an efficient azaspiroindolenine rearrangement; this achievement is revisited in detail. Upon completion of the first-generation total synthesis, we explored some interesting mechanism-level issues with regard to the key azaspiroindolenine rearrangement. These investigations provided valuable insights into the mechanism of racemization during the azaspiroindolenine rearrangement en route to synthetic phalarine. In addition, in the course of these studies, we demonstrated the Pictet-Spengler capture reaction for C(2)-aryl indoles, and successfully isolated the elusive azaspiroindolenine intermediate of the Pictet-Spengler reaction. Key insights into the remarkably subtle stereoelectronics that govern this rearrangement for C(2)-arylated indoles are discussed.
authors: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065.
authors: John D
authors: JD
authors: Trzupek
authors: Chaomin
authors: C
authors: Li
authors: Collin
authors: C
authors: Chan
authors: Brendan M
authors: BM
authors: Crowley
authors: Annekatrin C
authors: AC
authors: Heimann
authors: Samuel J
authors: SJ
authors: Danishefsky