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Concise Stereoselctive Synthesis Of Aspidoalbidine Alkaloids & Spliceostatin Derivatives

thesis
posted on 12.10.2021, 15:06 by Josh R BornJosh R Born
Enantioselective syntheses of hexacyclic aspidoalbidine alkaloids (+)-fendleridine and (+)-acetylaspidoalbidine are described. These syntheses feature an asymmetric decarboxylative allylation and photocyclization of a highly substituted enaminone. Also, the synthesis highlights the formation of a C19-hemiaminal ether via a reduction/condensation/intramolecular cyclization cascade with the C21-alcohol. The present synthesis provides convenient access to the aspidoalbidine hexacyclic alkaloid family in an efficient manner.
A copper-catalyzed cross-coupling is described. Use of Cu(I) salts in the presence of allyl bromides and organostannyl furans were found to undergo catalytic turnover under ambient conditions and afford the coupled products in good to great yields. Model substrate screening led to conditions used in the concise formal synthesis of FR901464 analogues. Optimization of the described coupling step led to suppression of undesired isomers and byproducts affording the desired diene coupled product in high yield, stereo-, and regioselectivity on a multigram scale. Novel protection of the resulting diene moiety as an unconventional protecting group, and a facile four-step single column chromatographic stereoselective sequence are also reported.

History

Degree Type

Doctor of Philosophy

Department

Chemistry

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Arun K. Ghosh

Additional Committee Member 2

Mark Lipton

Additional Committee Member 3

Abram Axelrod

Additional Committee Member 4

Chris Uyeda