NOVEL APPROACHES TO STRYCHNOS AND ASPIDOSPERMA ALKALOIDS
Genre
Thesis/DissertationDate
2015Author
Zhao, SenzhiAdvisor
Andrade, Rodrigo B.Committee member
Andrade, Rodrigo B.Davis, Franklin A.
Sieburth, Scott McNeill
Cannon, Kevin C.
Department
ChemistrySubject
ChemistryChemistry, Organic
Aspidosperma Alkaloids and Bis-aspidosperma Alkaloids
Melotenine A
Methodology Development
Strychnos Alkaloids and Bis-strychnos Alkaloids
Sungucine
Total Synthesis of Natural Products
Permanent link to this record
http://hdl.handle.net/20.500.12613/4093Metadata
Show full item recordDOI
http://dx.doi.org/10.34944/dspace/4075Abstract
All Strychnos and Aspidosperma alkaloids possess a core pyrrolo[2,3-d]carbazole ABCE tetracycle. In order to develop an efficient and divergent methodology for the synthesis of Strychnos alkaloids, a streamlined synthetic sequence to the ABCE tetracycle has been developed. It features a Mitsunobu activation of an N-hydroxyethyl gramine intermediate and subsequent intramolecular aza-Baylis-Hillman reaction. This method was first applied in the total synthesis of (±)-alstolucine B. Additional key steps in the synthesis included (1) chemoselective intermolecular and intramolecular Michael additions and (2) a Swern indoline oxidation. The second application of this method was in the first total synthesis of (-)-melotenine A, a novel rearranged Aspidosperma alkaloid with potent biological activity. Additional key steps in the synthesis included (1) a Piers annulation of a vinyl iodide and a methyl ketone to prepare the D ring and (2) a site-selective intermolecular vinylogous aldol reactionADA compliance
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Synthesis of Bis-Strychnos Alkaloids (–)-Sungucine, (–)-Isosungucine, and (–)-Strychnogucine B from (–)-StrychnineIt was developed a concise synthetic route resulting in the first syntheses of bis-Strychnos alkaloids (-)-sungucine, (-)-isosungucine, and (-)-strychnogucine B from commercially available (-)-strychnine. Employing a highly convergent synthetic strategy, it was demonstrated that both Strychnos monomers could be efficiently prepared from commercially available (-)-strychnine. The venerable Mannich reaction was enlisted to join the two Strychnos monomers in a biomimetic fashion. Subsequent epimerization and olefin isomerization yielded (-)-strychnogucine B. Functional group manipulation transformed (-)-strychnogucine B into (-)-sungucine and (-)-isosungucine. Computational chemistry was employed to rationalize the regiochemical course of key steps en route to the bis-Strychnos targets.
