Abstract:
Aigialomycin D is a fungal natural product possessing kinase inhibition properties. It
is a member of a class of compounds known as the resorcylic acid lactones, a expansive
group containing compounds exhibiting a vast array of biological activities. These include
kinase and Hsp90 inhibition, highly desirable properties in the drug development field.
This research project sought to capitalise on previous work involving the successful total
synthesis of aigialomycin D. By developing the synthetic methodology, analogues of
aigialomycin D could be prepared for biological testing to obtain valuable structure-activity relationship information. The focus of this thesis involves the successful synthesis
of aigialomycin D diastereomer, 5',6'-epi,epi-aigialomycin D and the attempted synthesis
of 100-epi-aigialomycin D, via the synthetic strategy developed previously in combination
with enantiomeric starting material fragments ...
The synthesis of functional group analogues, 6'-oxo-aigialomycin D, 7',8'-cyclopropyl
aigialomycin D and 5-chloro-agialomycin D were also attempted via derivatisation of
late-stage intermediates in the aigialomycin D synthesis. The thesis herein recounts the
successes and failures in the synthesis of various aigialomycin D analogues ...
