De novo synthetic approaches to aminosugar containing natural products: forosamine, purpurosamine C and 3'-o-forosaminyl-griseusin A.

• Online Access: http://hdl.handle.net/2047/D20328151

The aminosugar, more specifically deoxyaminosugar, motif plays an important role in the biological and physical properties of many natural products (e.g., gentamicin and 3'-O-forosaminyl-griseusin A). The charged basic amino group (i.e., protonated amine) of the glycosyl moiety is critical to their broad range of biological activities, such as the antibiotic, antifungal, and anticancer activities. The antibiotic 3'-O-forosaminyl-griseusin A is a glycosylated member of pyranonaphthoquinone natural products with a stereochemically undefined aminosugar moiety assigned as forosamine at the C-3'. The first project outlined in this dissertation was designed to address the glycosylated forosamine structural problem. A regio- and stereocontrolled divergent method was developed for the installation of all the possible forosamine stereomers. Twelve forosaminyl glycosides, including all the possible stereoisomeric forosaminyl lactone building blocks for 3'-O-forosaminyl-griseusin A, were prepared via an 11-step de novo asymmetric approach resulting in a 6-15% overall yield of - and -forosamine. The second project outlined in this dissertation describes a high efficiency linear asymmetric synthesis of purpurosamine C, one of the two aminosugar components of the antibiotic gentamicin C1a. Three key reactions, a Grieco elimination, acid-catalyzed one-pot glycosylation, and a one-pot reductive amination were explored to give -purpurosamine C in a 14.5% overall yield in seven steps from an achiral N-Cbz protected furan ketone. The last project outlined in this dissertation summarizes the efforts towards the enantioselective total synthesis of the pyranonaphthoquinone natural product 3'-O-forosaminyl-griseusin A. The aglycon building block, a bromonitrilequinone, was successfully synthesized in 14-step synthesis from dihydroxy naphthalene. The lactone forosamine stereoisomer building blocks were successfully synthesized in 11-step synthesis from ethyl sorbate and acetyl furan. Future work will be a double metal-halogen exchange strategy to give the griseusin spiroketal ring system.