Abstract:
The first part of this thesis describes the successful synthesis of the FG ring fragment 178 of the structurally complex marine toxins, the pectenotoxins. The synthesis hinges on functional group manipulations of the advanced olefin-(Z) 179 to install the tetrahydrofuran and tetrahydropyran ring systems. Olefin-(Z) 179 is itself obtained by the cis selective Wittig olefination of aldehyde 180 and the phosphorus ylide derived from phosphonium salt 181. Key stereocentres of these two fragments are installed using a Katsuki-Sharpless asymmetric epoxidation and a Sharpless asymmetric dihydroxylation reaction, respectively.
The second part of this research presents synthetic attempts to access the fungal metabolites cephalosporolides E and F (290). These compounds contain the small but interesting β,γ-fused-[4.4]-spiroacetal-γ-lactone moiety which is a functional group found in seven known natural products, and has until recently eluded the synthetic chemist.
A Fukuyama coupling reaction was initially proposed to prepare advanced precursor ketone 474 but proved to be unsuccessful in our hands. A variant of the original Fukuyama reaction was successfully employed to obtain the same advanced ketone 474 but low yielding reactions combined with the delicate nature of this structure posed an insurmountable bottleneck in the planned synthetic strategy. Based on results of the research presented herein, the synthetic strategy towards this family of natural products was revised.
