Biomimetic total synthesis of meroterpenoid natural products
File(s)
Author(s)
Ma, Tsz Kan
Type
Thesis
Abstract
Meroterpenoids belong to a class of natural products that are biosynthesised via a mixed polyketide-terpenoid pathway. Meroterpenoids are reported to have a range of promising antibiotic, anti-tumor, anti-HIV and anti-diabetic activities. To fully evaluate their therapeutic potential, a concise and flexible synthetic route is required to access these natural products and their analogues for parallel syntheses to assist future bioassay and structure-activity relationship (SAR) studies.
This thesis describes further developments and synthetic applications of the biomimetic polyketide aromatisation of β, σ-diketo dioxinones to produce resorcylates starting from commercially available terpene alcohols such as geraniol and trans, trans-farnesol. The resulting resorcylates are important intermediates which could be diversified into a selection of meroterpenoid natural products such as amorphastilbol, grifolic acid and grifolin via hydrolytic decarboxylation or saponification. Palladium catalysed oxidative cyclisation of resorcylates lead to the formation of chromene heterocycles to provide (±)-cannabiorcichromenic and (±)-daurichromenic acids. More complex polycyclic meroterpenoids such as the hongoquercins and the austalides could be accessed by subsequent cationic or radical anion polyene cyclisation.
This thesis describes further developments and synthetic applications of the biomimetic polyketide aromatisation of β, σ-diketo dioxinones to produce resorcylates starting from commercially available terpene alcohols such as geraniol and trans, trans-farnesol. The resulting resorcylates are important intermediates which could be diversified into a selection of meroterpenoid natural products such as amorphastilbol, grifolic acid and grifolin via hydrolytic decarboxylation or saponification. Palladium catalysed oxidative cyclisation of resorcylates lead to the formation of chromene heterocycles to provide (±)-cannabiorcichromenic and (±)-daurichromenic acids. More complex polycyclic meroterpenoids such as the hongoquercins and the austalides could be accessed by subsequent cationic or radical anion polyene cyclisation.
Version
Open Access
Date Issued
2019-02
Date Awarded
2019-05
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Barrett, Anthony G. M.
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)