UC Berkeley

In this two-part dissertation, several different strategies are developed to attempt concise synthesis of complex natural products. In the first part, a concise total synthesis of garsubellin A, is reported. Starting from commercially available 2-methyl cyclopentenone, this synthesis of garsubellin A was enabled by a series of powerful C-C bond forming reactions, including a tandem oxy-Cope/methylation reaction, a diketene annulation, a ring expansion reaction and a novel regioselective prenyl coupling reaction. Meanwhile, a novel palladium catalyzed Wacker-type oxidation was developed to construct the characteristic tetrahydrofuran ring of garsubellin A. As we hoped this synthetic strategy could serve as a modular synthetic solution of diverse PPAP meroterpenes, an enhanced substrate scope of the diketene reaction was reported.

In the second part of this dissertation, our synthetic studies of acutumine is described. In this chapter, a background introduction is first given, including the isolation and structure determination of acutumine alkaloids, biosynthetic studies, bioactivates of acutumine family, and the prior synthetic studies of (–)-acutumine. Meanwhile, several different strategies for achieving a concise total synthesis of (–)-acutumine were developed and discussed in this dissertation. A novel [3+2] cyclization protocol was developed, which, in three steps, converts commercially available starting materials to a [3.3.0] aza-bicyclic intermediate. From this advanced bicyclic intermediate, a series of efforts to transfer this advanced bicyclic intermediate to (–)-acutumine was explored and reported.