UCLA

Chapter one provides an overview of the history of the akuammiline alkaloids, including

their isolation, structural features, biological activity, and biosynthesis. This chapter provides a

discussion of synthetic efforts toward these intriguing alkaloids, in addition to detailed

descriptions of several recently completed total syntheses. Chapter two discusses an efficient

method to access the fused indoline ring system present in a multitude of bioactive molecules.

The strategy involves the condensation of hydrazines with latent aldehydes to ultimately deliver

indoline-containing products by way of an interrupted Fischer indolization sequence. The

method is convergent, mild, operationally simple, broad in scope, and can be used to access

enantioenriched products. In addition, the synthesis of furoindoline and pyrrolidinoindoline

natural products is demonstrated by the concise formal total syntheses of physovenine and

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debromoflustramine B. Chapter three explores the mechanisms of the Fischer indole synthesis

and competing cleavage pathways with SCS-MP2/6-31G(d) and aqueous solvation calculations.

Electron-donating substituents divert the reaction pathway to heterolytic N-N bond cleavage and

preclude the acid-promoted [3,3]-sigmatropic rearrangement. Chapters four reports the total

synthesis of (±)-aspidophylline A, one of many complex furoindoline-containing alkaloids that

has not been synthesized previously. Our route features a number of key transformations,

including a Heck cyclization to assemble the [3.3.1]-bicyclic scaffold, as well as a late-stage

interrupted Fischer indolization to install the furoindoline and construct the natural product's

pentacyclic framework.