Towards the synthesis of anthecularin and anthecotulides

Thesis

The work presented in this thesis mainly describes the discovery and development of methodology for the synthesis of anthecularin and anthecotulides, a family of unusual sesquiterpene lactones.

Firstly, two 1,3-dipolar cycloaddition approaches toward anthecularin have been evaluated, using either oxidopyrylium ylide chemistry (Path A) or carbonyl ylides, generated by rhodium-catalysed decomposition of diazo ketones (Path B). Synthesis of the key precursor for the diazo strategy was achieved but unfortunately no desired cycloadduct was isolated.

Secondly, an experimentally straightforward method to stereoselectively synthesise β-hydroxymethyl-α-methylene-γ-butyrolactones was developed using chromium or zinc. The synthetic utility of this methodology was demonstrated in syntheses of (±)-methylenolactocin, (±)-hydroxymatairesinol and, ultimately, (±)-hydroxyanthecotulide using a gold-catalysed Meyer-Schuster rearrangement.

Finally, the first asymmetric synthesis of (+)-anthecotulide has been achieved, in 6 steps from commercially available materials. During this synthesis the absolute configuration was established. Furthermore, a novel rhodium-catalysed enantioselective ene-yne cycloisomerisation was used to form the α-methylene-��-butyrolactone core.

Authors: Talbot, E

• Publication date: 2011
• DOI: 10.5287/ora-er55d207r
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: antimalarial; natural product synthesis; chromium allylation
• Subjects: Natural products; Organic synthesis; Asymmetric catalysis; Organometallic Chemistry