Synthesis of the Antimalarial Flindersial Alkaloids

The concept of mimicking nature to synthesize natural compounds has been successfully demonstrated in the synthesis of all the anti-malarial Flindersia alkaloids. Previous work on the biosynthesis of the related natural products borreverine and isoborreverine inspired us to synthesize racemic flinderoles A, B, and C in as few as three synthetic steps from simple and readily available materials. The development of reaction conditions for the dimerization of borrerine in the presence of acid is discussed in detail. The progress toward the enantioselective total synthesis of flinderoles A, B, and C is also presented. The retrosynthetic plan was inspired by the biomimetic synthesis of the flinderoles, in which an acid mediated amino cyclization would form the flinderole framework. Tryptamine and 3-butyn-2-one undergo a vinylogous Pictet-Spengler reaction to give a β-carboline, which opens to a 2-enone tryptamine in the presence of base. A BINOL catalyzed enantioselective conjugate addition of a vinyl boronic acid to the 2-enone tryptamine has been achieved. A pyrrolo[a]indole unit could be connected to another indole unit by a Sonagashira coupling reaction in a convergent manner.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Houston

Year dc:date.issued

2015

Author dc:creator

• Vallakati, Ravikrishna 1977-

Advisor dc:contributor.advisor

• May, Jeremy A.

Committee members dc:contributor.committeemember

• Gilbertson, Scott R.
• Thummel, Randolph P.
• Cuny, Gregory D.
• Xu, Shoujun

• Flinderoles, antimalarial, Biomimetic Synthesis, Organocatalysis

Statement dc:rights

• The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/10657/6552

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/6552