Studies towards the total synthesis of galanthamine and the total synthesis of 2-Benzoyl-9-azabicyclo[4.2.1]non-2-ene : phenyl analogue of (#+-#)Anatoxin-a
This thesisd escribess yntheticw ork carriedo ut on two separatep rojects.
(i) Synthetics tudiest owardst he total synthesiso f galanthamine
(ii) The total synthesis of 2-Benzoyl-9-azabicyclo[4.2.1 ]non-2-ene
Galanthamine is an amaryllidaceae alkaloid processing a rigid tetracyclic structure
with a fused dihydrobenzofuran onto a cyclohexenol and a bridging tertiary amine.
2-Benzoyl-9-azabicyclo[4.2.1]non-2-ene is an analogue of anatoxin-a, whereby the
acetyl side chain has been substituted with a benzoyl group. Anatoxin-a itself
possesses a 9-azabicyclo[4.2.1]nonane framework.
Although structurally very different they both share a common feature in that they
interact with acetylcholine receptors. Hence chapter 1 is an introduction to
Alzheimer's disease which is primarily caused by a lack of acetylcholine.
A literature review of the total syntheses of galanthamine and a background of
galanthamine is described in chapter 2, whilst chapter 3 details the forward synthesis
to the galanthamine framework but with a cyclopentenyl instead of a cyclohexenyl
moiety and subsequent attempts for the elaboration of the cyclopentenyl into its
corresponding cyclohexenyl moiety.
Chapter 4 and 5 describes the published total syntheses of anatoxin-a and analogues
of anatoxin-a, whilst chapter 6 concludes the total synthesis of the phenyl analogue of
anatoxin-a via a key selenium mediated transannular cyclisation of a Boc-(3-Lactam to
furnish the 9-azabicyclo[4.2. l]nonane ring system.