PROGRESS TOWARD A TOTAL SYNTHESIS OF THE MARINE ALKALOID PEROPHORAMIDINE

Open Access
Author:
Sacher, Joshua Ryan
Graduate Program:
Chemistry
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
August 06, 2009
Committee Members:
  • Steven M Weinreb, Thesis Advisor
Keywords:
  • carbonylation
  • intramolecular
  • Heck
  • alkaloid
  • synthesis
  • chemistry
  • organic
  • marine
  • perophoramidine
Abstract:
ABSTRACT Two strategies toward a synthesis of the marine alkaloid perophoramidine (1) have been investigated. Previous work utilizing a tandem Heck reaction/carbonylation strategy was initially reexamined, but was found to be unsuitable to access the natural product. The current strategy relies on a Suzuki-Miyaura coupling to form a substituted tetrahydropyridine core, which could undergo a halogen-selective intramolecular Heck reaction. The first generation of this strategy was plagued by an unexpected cyclization reaction that prevented the key Heck reaction from being examined. A modified approach was explored using a methoxy substituent in place of the desired C-ring bromine of perophoramidine in order to control the electronics of the Heck cyclization precursor to avoid the previously observed side reaction. The key Heck reaction was demonstrated to be effective, and further efforts are underway to complete a synthesis of perophoramidine.