Synthetic Investigations into Alotane Derived Sesterterpenoid Marine Natural Products.
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Phorbaketal A (I) and phorone A (II) are members of a growing family of biologically active sesterterpenoid natural products, derived from marine sponges. These compounds possess potent biological activities and intriguing molecular architectures, which have inspired efforts towards their total synthesis. Early work in this thesis describes how new methodology is developed aimed at the synthesis of phorbaketal A (I). The synthesis and subsequent treatment of the model hydroxyphenol III with PhI(OAc)2 led to the development of a new method for spiroketal synthesis via cascade oxidative dearomatisation. This new spiroketalisation method was then further elaborated for the total synthesis of phorbaketal A (I). This required the construction of the noralotane carbon skeleton IV, employing the union of the aryl aldehyde V and the propargylated geraniol VI. Treatment of the noralotane IV with PhI(OAc)2 gave the spiroketal VIII as a complex mixture of labile diastereomers. This new method for spiroketalisation ultimately proved unsuitable for the total synthesis of these spiroketal natural products. Following this, attempts at expanding the substrate scope for this new oxidative dearomatisation method were explored for the formation of a range of saturated spiroketals. v The second part of this thesis describes efforts towards the total synthesis of the related sesterterpenoid natural product phorone A (II). Considerable synthetic effort led to synthesis of the novel (Z)-bromoalkene IX and the drimane aldehyde X, which were coupled to give the ansellane alcohol XI, in a total of 17 steps. This work represents the first ever synthesis of the ansellane skeleton. Efforts to oxidise and cyclise the alcohol XI were initiated; however difficulties with eliminative dehydration prevented its conversion to phorone A (2). The final work in this thesis describes alternate coupling methods aimed at circumventing these unforeseen issues.
AuthorsShirley, Harold John
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