Synthetic Investigations into Alotane Derived Sesterterpenoid Marine Natural Products.
Abstract
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.
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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.
Authors
Shirley, Harold JohnCollections
- Theses [3827]