The Asymmetric synthesis of 2-epi-Prevezol C and the diastereoisomers of Quercivorol
thesisposted on 19.01.2017, 03:08 by Blair, Michael
The brominated secondary metabolites isolated from the polar fractions of the macroalga Laurencia Obtusa (Lamoroux), termed ‘Prevezols’ posses cytotoxic properties against a range of human carcinoma lines. These novel diterpenes contain unique molecular architectures with an incredibly rare and challenging syn-bromohydrin motif, to date unaddressed via total synthesis. This dissertation discloses the synthesis of the diterpene framework of Prevezol C, via a stereoconvergent allylic alkylation strategy of two monoterpene chirons, derived from the optically pure commercial mixture of cis- and trans- limonene oxide. The first part of this thesis is concerned with the separation and isolation of both the cis- and trans-limonene oxide isomers via a hydrolytic kinetic separation, to the corresponding limonene trans- diaxial and -diequatorial diols (Chapter 2), which are implemented as part of the synthesis of the 2-bromo epimer of Prevezol C (Chapter 3, Part 1). A novel free radical hydrodebromination strategy (Chapter 3, Part 2) was successfully employed as a means of accessing the naturally occurring synbromohydrin relationship found in the Eastern domain of the Prevezols, and several other secondary metabolites derived from the red algae species of Laurencia. Finally, a second total synthesis of the major and minor constituents of the ambrosia beetle Platypus quercivorus was also achieved (Chapter 4) via a palladium catalysed deoxygenation strategy of the limonene trans-diaxial and -diequatorial diols.