I. Total synthesis of aspidospermidine. II. An overview of the discorhabdin and makaluvamine marine alkaloids. III. Formal total synthesis of makaluvamine F and studies toward the total synthesis of discorhabdines A, B, and D

Chapter 1 describes the total synthesis of the parent compound of the Aspidosperma alkaloids, (±)-aspidospermidine. The key step of the synthesis is an intramolecular cascade reaction that simultaneously forms the B, C, and D rings of aspidospermidine. Initial studies attempted to synthesize the cascade precursor by a Negishi, Pd catalyzed, cross coupling reaction, but were unsuccessful. Ultimately, the desired compound was synthesized from readily available methyl 3-ethyl-2-oxocylopentanecarboxylate. A high-yielding method of closing the E ring is also described, which allowed aspidospermidine to be synthesized in 5.9% yield over 13 steps.; Chapter 2 provides an in-depth overview of the literature that has been published on the discorhabdin and makaluvamine alkaloids. This overview includes the isolation, biological activity, and proposed biosynthetic routes of these natural products, as well as the research that has been done towards the total synthesis of both the makaluvamines and the discorhabdins.; Chapter 3 describes the formal total synthesis of marine pyrroloiminoquinone alkaloid, makaluvamine F. Three routes to the thiohemiaminal containing ring system are discussed. The first route described attempted the oxidation of a thiol to a sulfenyl halide, and an intramolecular oxidative transfer to form an acyl imine. The second route discussed explored the use of a [3,3]-sigmatropic rearrangement to form the ring system in a manner similar to the Fischer indole synthesis. The final route described relied on the ability of DIBAL-H to reduce a nitrile to an imine, with simultaneous deprotection of a thiocarbamate. This route allowed the formal total synthesis of makaluvamine F to be accomplished in 10.6% yield over 9 steps. Efforts towards the total synthesis of discorhabdins A, B, and D are also discussed in this chapter.