Studies towards sustainable syntheses of Schisandra triterpenes

Thesis

Triterpenes from the Schisandraceae family, have attracted the attention of the synthetic community due to their intricate structures and potential anti-HIV bioactivity. However, the previous syntheses of these molecules were hampered by lengthy routes, inefficient strategies, toxic and hazardous chemicals and excessive protecting groups and chromatographic purifications. Here we describe efforts to address these limitations by employing strategies that achieve efficient, scalable and sustainable syntheses of the key building blocks towards lancifodilactone I and rubriflordilactones A and B.

Our AB ring synthesis introduces a novel paradigm for tetrahydrofuran ring formation through a strategic ring expansion rearrangement of a cyclobutanol, which is derived from a cyclobutene-containing terpene chiral pool starting material. This resulted in a highly efficient scalable synthesis of the AB rings in only 7 steps, devoid of chromatographic separations, with just two crystallisations required.

Our FG ring synthesis explored the reactivity of an unusual vinylogous ester within a locked cis-decalin system, obtained via concise synthetic sequence from a carbohydrate chiral pool. However, the unanticipated challenges of ketone alpha-methylation in this bicyclic system hindered the continuation of this approach.

Our diyne fragment features the use of organogermanium chemistry to distinguish between two similar alkynes. This streamlined approach resulted in the synthesis of the diyne fragment in 9 steps. Unification of the AB rings and the diyne fragment constitutes a formal synthesis of rubriflordilactone A in 17 steps (LLS).

Authors: Kravljanac, P

• DOI: 10.5287/ora-obq1xbzg1
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: natural products; total synthesis; sustainable organic chemistry
• Subjects: Chemistry, Organic