Studies Towards the Total Synthesis of Illicium Derived Neolignans

Giangone, Salvatore (2023) Studies Towards the Total Synthesis of Illicium Derived Neolignans. MRes thesis, University of Nottingham.

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Illicium derived neolignans are a class of structurally diverse secondary metabolites which arise in nature from the chemical manipulation of chavicol units. There is a growing interest in Illicium derived neolignans as they have been shown to provide neuroprotective effects. Recent studies have shown that neolignans can facilitate the growth and protection of developing neurons.

This thesis presents a bioinspired approach towards the challenging synthesis of simonsol A: a sesqui-neolignan with a characteristic [3.3.1] ring system. The key Claisen rearrangement in the synthesis of simonsol A has been calculated to be high and at 45.7 kcal mol. Untested catalytic methods were attempted to overcome this barrier but were unsuccessful. A Lewis-acid catalysed approach to overcome this barrier was also unsuccessful as an outcompeting side-reaction led to the isolation of an unwanted species. This species was fully characterised by IR and NMR spectroscopy, and X-ray crystallography. The rotational barrier for this unwanted species was calculated and reasoning for its diastereotopicity is provided. The synthetic route towards simonsol A presented herein was proved to be defunct on the basis of a competitive allyl group migration.

Studies towards the synthesis of simonol B are presented. A model system containing a dihydroxyl-cyclohexylbenzofuran core has been synthesised, providing proof of concept work which shows that simonol B can be accessed via simonsol F. We have determined that the Mukaiyama hydration is not compatible with substrates containing free hydroxyl or arylallyl groups. An NOE interaction observed for the model system between the two alcoholic protons suggested that the relative stereochemistry between the adjacent hydroxyl groups was syn. This was confirmed by a comparison between experimental 13C NMR spectroscopic values and computationally predicted values for the anti and syn diastereomers of the model system.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Denton, Ross
Keywords: lignans, neolignans, metabolites, plant metabolites, phenolic compounds, biosynthesis
Subjects: Q Science > QK Botany > QK710 Plant physiology
Q Science > QP Physiology > QP501 Animal biochemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 74524
Depositing User: Giangone, Salvatore
Date Deposited: 12 Dec 2023 04:40
Last Modified: 12 Dec 2023 04:40

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