Abstract:
The first part of this thesis focuses on the successful synthesis of the morpholine spiroketal acortatarin A (17). The synthesis of acortatarin A (17) relied on the key Maillard-type condensation between amino alcohol 158a and dihydropyranone 83. Amino alcohol 158a is in turn obtained by azide opening of epoxide 161a, followed by reduction. Dihydropyranone 83 was prepared in excellent yield from furan 94 using an Achmatowicz oxidation/rearrangement. The second part of this thesis describes synthetic studies towards the fungal secondary metabolite tenuipyrone (174) and its 3-dehydroxy analogue 200. The unique tetracyclic structure contains a spiroketal fused to a biologically relevant 2-pyrone moiety. A tandem Stille-Sonogashira cross coupling sequence afforded the key spiroketal precursor 240 in high yields. Attempted sequential deprotection/spiroketalisation to access spiroketal 200 was unsuccessful. Further studies conducted on enynone 202 and 239 using a Hg(II) catalysed alkyne hydration or Au(I) catalysed alkyne cyclisation failed to deliver the expected 1,3-dicarbonyls 229a and 229b. Importantly, it was established that -ynones were not suitable substrates for the desired metal catalysed spiroketalisation or Hg(II) catalysed hydration. Based on results of the research presented herein, an alternative synthetic strategy to access the spiroketal ring system towards tenuipyrone was proposed.