Biomimetic synthesis of meroterpenoid natural products using dearomatization strategies

Synthetic efforts towards various meroterpenoid natural products based on biosynthetic speculation were undertaken in order to gain biosynthetic insight and to develop efficient syntheses of some structurally complex, biologically active compounds. The first total synthesis of the PPAP natural product garcibracteatone was achieved in four linear steps from phloroglucinol (0.6% overall yield). The key biomimetic synthetic step was an oxidative radical cyclization cascade reaction, where four new carbon-carbon bonds, four new carbocyclic rings and five new stereocentres were formed in the one step. The first total synthesis of merochlorin A was achieved in five linear steps from methyl-3,5- dimethoxyphenylacetate (6% overall yield). The key biomimetic synthetic step was a [5 + 2] cycloaddition reaction induced be oxidative dearomatization to form the bicyclo[3.2.1]octane core. The first total synthesis of the napyradiomycin natural product naphthomevalin was achieved in 11 steps from methyl-3,5-dimethoxyphenylacetate (1.4% overall yield). The key biomimetic synthetic step was a thermal α-ketol rearrangement reaction to form the naphthoquinone core of the napyradiomycins. The synthetic naphthomevalin was additionally converted into A80915G via a biomimetic Sɴ2 epoxidation reaction, and into napyradiomycin A1 via a chemoenzymatic reaction.Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2016