- Part 1: A Diels-Alder Approach to the Synthesis of Novel Analogues of the Natural
Due to the prevalence of biaryl motifs in natural product synthesis, the Carter
research group has been exploring the utility of a Diels-Alder approach to biaryl
synthesis. The Diels-Alder approach involves a [4+2] cycloaddition between an
acetylene dienophile and a cyclohexadiene, followed by subsequent [4+2]
cycloreversion. This method of biaryl synthesis introduces numerous advantages
compared to the traditional metal-mediated biaryl synthesis procedures, including a lack
of environmentally hazardous transition metals.
The Diels-Alder approach has been used by the Carter group to synthesize the
natural product siamenol. This carbazole alkaloid, isolated from the Murraya siamensis
shrub, has been found to possess moderate activity in the inhibition of the human
immunodeficiency virus (HIV). Previously, synthesis of siamenol had been based on the
traditional metal-mediated cross-coupling approach. Based on this initial synthesis, a
series of novel analogues of siamenol have been synthesized using the Diels-Alder
approach to biaryl synthesis. This project focuses on the synthesis of four such
analogues of siamenol.
Part 2: Advances in Proline-Based Enantioselective Organocatalysis and its Application
to a Novel Synthesis of the Natural Product Aconitine
Organocatalysis, while not a novel concept, has made significant strides in the
last decade with the advent of improved methods of enantioselective organocatalysis.
Particular advances have been made in the use of proline-based organocatalysts in
catalyzing such reactions as aldol, Mannich and Michael reactions in a highly
enantioselective fashion. The Carter Group has utilized Hua Cat, a proline-based
sulfonamide, to catalyze a series of [2.2.2] bicyclizations based on a Mannich reactionrelated
mechanism. This approach has been utilized to form a precursor to the natural
product aconitine, a known analgesic and antipyretic. The key [2.2.2] bicyclization step
proceeded in a high-concentration (1.0 M), room temperature reaction that produced the
target [2.2.2] octane with a 57% yield and 99% e.e. Further considerations toward the
synthesis of aconitine are also discussed.