Abstract
The DMOA-derived meroterpenoids are a vast family of often complex natural products with a variety of biological relevant properties. One such natural product is spiroaspertrione A (35), isolated from the endophytic fungus Aspergillus sp. TJ23. Spiroaspertrione A (35) was found to possess bacteriostatic effects against methicillin-resistant Staphylococcus aureus, along with the potentiation of oxacillin. The unique spiro[bicyclo[3.2.2]nonane-2,1’-cyclohexane] carbocyclic core of 35 poses a unique synthetic challenge, wherein this thesis describes several strategies toward the first total synthesis of spiroaspertrione A (35).
The investigation of synthetic strategies first developed by Dr. Michael Badart were undertaken, where the key retrosynthetic disconnections divided the ABCDE-ring system of 35 into two fragments of similar complexity, denoted as the AB-ring system (99) and the DE-ring system (100).
Building upon the foundational work by Badart, this thesis describes the development of an efficient and robust route to the ABDE-adduct. The key step in this route was a Mukaiyama–Michael addition which provided the desired adduct 132 and its protodesilylated counterpart, 163.
Efforts toward the late-stage installation of the highlighted methyl group on the DE-ring system was not forthcoming. Prompting re-examination of the strategy, namely, the incorporation of this methyl group into the initial building blocks. This provided, for the first time, the fully elaborated DE-ring system (100).
Disappointingly, despite significant effort, this substrate was found to be unreceptive to the aforementioned Mukaiyama–Michael reaction conditions. This work suggests a re-evaluation of the synthetic strategy to access spiroaspertrione A (35) is necessary, in particular the spirocyclisation strategy.