Studies towards the total synthesis of manzamine A

Thesis

This thesis describes studies towards the total synthesis of manzamine A (9), a marine alkaloid. Two routes are presented.

The first route applied a novel palladium-catalysed arylative allene spirocyclisation cascade to the synthesis of manzamine A (9). In the first generation, a short route was developed to access the tricyclic ACE core 263a in only nine steps. The second generation applied the palladium-catalysed cascade to a similar system which utilised non-terminal allene pro-nucleophile 450 in an attempt to access a homologated derivative of the ACE core.

The second route relied on a diastereoselective Michael addition between nitro-olefin 473 and 8,5-fused ring system 146 comprising rings C and E of manzamine A (9). Further elaboration of the Michael addition product enabled the synthesis of tetracyclic ABCE core precursor 464 to be carried out and preliminary investigations into ring B formation were investigated.

Authors: Hawkins, A

• Publication date: 2013
• DOI: 10.5287/ora-xk0ja1nyx
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: ORGANIC CHEMISTRY; TOTAL SYNTHESIS; MANZAMINE A
• Subjects: Organic synthesis; Chemistry & allied sciences; Synthetic organic chemistry; Natural products; Organic chemistry