Total synthesis of (-)-pyridovericin and synthetic studies towards aetheramide B

In this thesis, two projects involving the total synthesis of natural products are presented.
The first part gives an overview on neurodegenerative diseases and introduces the
neuritogenic pyridopolyene natural product (–)-pyridovericin. The enantioselective total
synthesis of (–)-pyridovericin is presented. The key steps were an enantioselective,
iridium-catalyzed hydrogenation of an enoate and an E-selective Horner-Wadsworth-
Emmons reaction. The complex pyridopolyene structure was then truncated and the
neuritogenic core structure identified. Truncated natural product analogs were
synthesized and successfully implemented in a neuritogenic surface material.
The second part reviews the current state of research on HIV and AIDS. Our efforts
towards the total synthesis of the recently isolated HIV-inhibitory natural product
aetheramide B are reported. Three advanced building blocks were synthesized
enantioselectively in good yields. The key steps involved the enantioselective
hydrogenation of an enamide to form an amino ester, the diastereoselective alkynylation
of a homobenzylic aldehyde and the enantioselective reduction of a bromoenone. The
building blocks were then successfully coupled to form the macrocyclic depsipeptide
core structure. The macrocyclic core of aetheramide B was then synthesized in a
macrolactonization reaction.