Lessons from the total synthesis of (±)-phalarine: Insights into the mechanism of the Pictet-Spengler reaction Journal Article


Authors: Trzupek, J. D.; Li, C.; Chan, C.; Crowley, B. M.; Heimann, A. C.; Danishefsky, S. J.
Article 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 C2-arylated indoles are discussed. © 2010, IUPAC.
Keywords: total synthesis; synthesis (chemical); natural products; reaction intermediates; metabolites; pictet-spengler reactions; phalarine; pictet-spengler reaction; rearrangement; nitrogen compounds
Journal Title: Pure and Applied Chemistry
Volume: 82
Issue: 9
ISSN: 0033-4545
Publisher: Walter de Gruyter GmbH  
Date Published: 2010-04-06
Start Page: 1735
End Page: 1748
Language: English
DOI: 10.1351/pac-con-09-11-14
PROVIDER: scopus
PMCID: PMC2920150
PUBMED: 20711493
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: PACHA" - "Source: Scopus"
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